AU2014259526A1 - Methods of treating ankylosing spondylitis using IL-17 antagonists - Google Patents

Abstract

H:dalinieroveNRPorbl\DCC\DARM946965_.dcx-3/I 1(2014 The disclosure relates to novel regimens for treating an inflammatory arthritis, e.g., rheumatoid arthritis (RA) patients, e.g., high risk RA patients, which employ a therapeutically effective amount of an IL-1 7 antagonist, e.g., IL- 17 binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL- 17 receptor binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof).

Description

H:dar lnwinvoen\NRPortbOWCC ARM936040 1.docx-2 9 /ID/2014 METHODS OF TREATING RHEUMATOID ARTHRITIS USING IL-17 ANTAGONISTS This application is a divisional of Australian Patent Application No. 2011325134, the entire content of which is incorporated herein by reference. This disclosure claims priority to US Provisional Patent Application No. 61/410,533, filed November 5, 2010, the disclosure of which is incorporated by reference herein in its entirety. TECHNICAL FIELD The disclosure relates to novel methods for treating rheumatoid arthritis, which employ a therapeutically effective amount of an IL-17 binding molecule, e.g., an IL-1 7 antibody, such as the AIN457 antibody (which is also known as "secukinumab"). BACKGROUND OF THE DISCLOSURE Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of unknown etiology. It is characterized by symmetric synovitis leading to cartilage damage and joint destruction and can be complicated by numerous extra-articular manifestations. Given the presence of autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA), RA is considered an autoimmune disease. RA is generally a progressive disease with functional status decline, significant morbidity and premature mortality seen in established RA. The disease can occur at any age, with a peak incidence between the fourth and sixth decades. The goal of long-term RA treatment is disease remission. Disease-modifying antirheumatic drugs (DMARDs), a heterogenous collection of agents grouped by use and convention, are the first line of treatment for RA patients. DMARDs are used to reducejoint swelling and pain, decrease acute-phase markers, limitthe progression ofjoint damage and to improve joint function. DMARDs, most often methotrexate (MT.X), are prescribed upon disease diagnosis (i.e., early RA), usually before the development of erosive disease and the deformities seen in established RA. MTX therapy is initiated if pain and synovitis persist (especially if function is compromised), and additional DMARDs (with or without steroids) may be added to achieve disease control. Unfortunately, only about 2/3 of patients respond to DMARDS, and DMARDs only partially control established RA disease. - 1- WO 2012/059598 PCT/EP2011/069476 54388 FF Radiological progression continues even in the 5 - 20% of DMARD-treated RA patients that achieve remission or clinical improvement that approaches remission. DMARDS also have many adverse effects (e.g., liver damage, bone marrow suppression and severe lung infection) that limit their prolonged use. Due to the inadequate responses and dangers associated with prolonged DMARD treatment, biologics have been introduced as second line RA treatments. In general, anti-TNF agents (Cimzia@, Enbrel®, Humira@, Remicade@, Simponi@) are the first biologies used in DMARD-failure and DMARD-inadequate responder patients, and a TNF inhibitor is often combined with MTX (or another DMARD) to aggressively treat established RA. Unfortunately, 30 - 40% of patients with established RA fail to respond to TNF-4 antagonists and the majority of those that respond initially do not achieve complete remission or lose response over time. Concerns have also been raised about the short and long-term tolerability and safety of chronic biologic treatment, most notably the reactivation of serious infections (e.g., tuberculosis infections), liver toxicity, increased cardiovascular disease, induction (or exacerbation of) demyelinating conditions, and increased incidence of malignancy due to TNF-alpha antagonisim. M. Khraishi (2009) J. Rheumatol SuppL. 82:25-321 Salliottet AL(2009) Ann. Rheum. Dis 68:25 32. However, a TNF inhibitor is usually continued unless it becomes ineffective or an adverse event arises, at which point a clinician may switch to either a different TNF inhibitor or a biological with a different mechanism of action (e.g., Kineret @ [IL-l R antagonist], MabThera® [CD20 antagonist], Orencia@ [CTLA4 fusion protein] or Actemra® [IL-6 receptor antagonist]). Scott et al. (2010) The Lancet 376:1095-1108. Given the aforementioned problems with current RA therapy, there is a need to develop new treatments for RA patients. SUMMARY OF THE DISCLOSURE Secukinumab, a new biological in clinical development for RA, is a high-affinity fully human monoclonal anti-human antibody that inhibits Interleukin-1 7A activity. In an RA proof of-concept (PoC) study, patients with active RA who were on a stable dose of MTX were dosed in rising single and then 2 doses (21 days apart) with secukinumab at 1mg/kg, 3mg/kg and 10mg/kg intravenously. Hueber et a]. (2010) Sci TransL Med. 2(52):52-72. Treatment with - 2 - Ii:"REOlierwoveNRPoribDCRF.O5255877 _Id-22/07/2013 -3 secukinumab resulted in rapid improvement of the clinical manifestations of RA in many patients compared to placebo. These data provide evidence that neutralization of IL-17A is likely to be efficacious in RA patients with active RA. However, since patient response to biological treatment is variable and it is desirable to avoid providing drug to patients who will be resistant thereto, we have sought methods of treating RA that first identity those patients most likely to respond favorably to antagonism of IL-17. We have identified an RA subgroup having patients that display an improved likelihood of responding to IL- 17 antagonism, whom we have named "high risk RA patients". Thus, in one or more aspects the present invention may advantageously provide methods of identifying and treating "high risk RA patients" using a therapeutically effective amount of an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof). In one or more aspects the present invention may advantageously provide methods of determining the likelihood that an RA patient will respond to treatment with an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof), by determining whether that patient is a high risk RA patient. In one or more aspects the present invention may advantageously provide methods of treating an inflammatory arthritis, e.g., AS, RA and PsA, using a therapeutically effective amount of an IL-17 antagonist, e.g., IL-1 7 binding molecule (e.g., IL-I 7 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof), by delivering such IL 7 antagonist as part of a therapeutic regimen, e.g., during an induction regimen and a maintenance regimen. In one aspect the present invention provides a method of treating rheumatoid arthritis (RA) comprising administering an IL-17 antibody to a patient in need thereof, wherein the IL-17 antibody is: a) administered to a patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; and qAR [hE 1wown~lRPur \DCC\REC\,S$5g17I1.doc-22/D7/2013 -3A b) thereafter administered to the patient as a dose of about 75 mg - about 150 mg every month, wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL- 17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Prol26, 11e27, Va1128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp8O on the other chain, wherein the IL-17 antibody has a KD of about 100 200 pM, and wherein the LL-17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides a method of treating rheumatoid arthritis (RA) comprising administering an 1L-17 antibody to a patient in need thereof, wherein the IL-17 antibody is: a) administered to a high risk RA patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; and b) thereafter, is administered to the patient as a dose of about 75 mg - about 150 ng every month, beginning one month from delivery of the third dose, wherein the IL- 17 antibody binds to an epitope of an IL- 17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val 124, Thrl25, Prol26, Ile127, Vall28, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL-17 antibody has a Ko of about 100 200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides a method of treating a rheumatoid arthritis (RA) patient comprising administering an IL-17 antibody to the patient, wherein the IL-17 antibody is: a) is administered to the patient during an induction regimen that provides a mean maximum plasma concentration (Cm) of the IL-17 antibody of about 360 pg/ml; and b) thereafter, is administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL-17 antibody between about 8 gg/ml - about 30 pig/ml; and/or ii) a mean AUC tau at steady state of about 331 mg*day/L - about 1323 mg*day/L, jI:ARE.CM\Io Rn ontrbl\DCCREHC255977_ .d-22D7/203 -3B wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Vall24, Thr125, Prol26, Ile127, Va1128, Hisl29 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL- 17 antibody has a KD of about 100 200 pM, and wherein the IL- 17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides a method of treating a rheumatoid arthritis (RA) patient comprising administering a IL-17 antibody to the patient, wherein the IL- 17 antibody: a) is administered to the patient during an induction regimen that provides a mean maximum plasma concentration (Cmax) of the IL- 17 antibody of about 401 gg/ml; and b) thereafter, is administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 antibody of about 9.4 fig/ml - about 31 pg/ml; and/or ii) a mean AUC tau at steady state of about 314 mg*day/L - about 1256 mg*day/L, wherein the IL- 17 antibody binds to an epitope of an IL- 17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val l24, Thr125, Pro l26, le 127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp8O on the other chain, wherein the IL-17 antibody has a K 0 of about 100 200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides a method of determining the likelihood that an RA patient will respond to treatment with an IL- 17 antibody, comprising assaying a sample from the patient for a) rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and b) C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CR9 and an ESR, i4:REFfntenwa'NRPrkbl\DCCREC5255877_Ldoc-22?7/2l3 - 3C wherein the patient is likely to respond to treatment of RA with the IL- 17 antibody if the patient is RF+, ACPA +, or RF+ and ACPA +; and the patient has a high level of CRP, a high ESR, or a high level of CRP and a high ESR. In one aspect the present invention provides use of an IL-17 antibody in the manufacture of a medicament for the treatment of rheumatoid arthritis (RA), wherein the medicament is formulated such that the IL-17 antibody is: a) administered to a patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; and b) thereafter administered to the patient as a dose of about 75 mg - about 150 mg every month, wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL- 17 protein chains, said epitqpe comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thrl25, Pro126, le127, Vall28, Hisl29 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp8O on the other chain, wherein the IL-17 antibody has a KD of about 100 200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides use of an IL-17 antibody in the manufacture of a medicament for treating rheumatoid arthritis (RA), wherein the medicament is formulated such that the IL-17 antibody is: a) administered to a high risk RA patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; and b) thereafter, is administered to the patient as a dose of about 75 mg - about 150 mg every month, beginning one month from delivery of the third dose, wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Vall24, Thr125, Pro126, Ile127, Vall28, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL- 17 antibody has a K 0 of about 100 200 pM, and wherein the IL- 17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides use of an IL- 17 antibody in the manufacture of a medicament for treating a rheumatoid arthritis (RA) patient, wherein the medicament is formulated such that the IL-17 antibody: a) is administered to the patient during an induction regimen that provides a IL\RElInierovRNrur VCORE 5255X77_ Ldo-22/i203 -3D mean maximum plasma concentration (Cmx) of the IL-17 antibody of about 360 pg/ml; and b) thereafter, is administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 antibody between about 8 pg/ml - about 30 pg/ml; and/or ii) a mean AUC tau at steady state of about 331 mg*day/L - about 1323 mg*day/L, wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, ValI24, Thrl25, Pro126, Ile127, Vall28, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL-17 antibody has a K 0 of about 100 200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks. In one aspect the present invention provides use of an IL-17 antibody in the manufacture of a medicament for treating a rheumatoid arthritis (RA) patient, wherein the medicament is formulated such that the IL-17 antibody: a) is administered to the patient during an induction regimen that provides a mean maximum plasma concentration (Cax) of the IL-17 antibody of about 401 pg/ml; and b) thereafter, is administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL-17 antibody of about 9.4 pg/ml - about 31 pg/ml; and/or ii) a mean AUC tau at steady state of about 314 mg*day/L - about 1256 mg*day/L, wherein the IL-1 7 antibody binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thrl25, Prol26, llel27, ValI28, Hisl 29 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL-17 antibody has a K 0 of about 100 200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks.

Jtklanime I dor DIU LiAKW94 ix-J i 11RU4 -3E Accordingly, disclosed herein are methods of treating rheumatoid arthritis (RA), comprising administering a therapeutically effective amount of an IL-17 antagonist to a high risk RA patient. Disclosed herein are also methods of treating rheumatoid arthritis (RA), comprising: a) selecting a patient for treatment on the basis of the patient being a high risk RA patient; and b) administering a therapeutically effective amount of an IL-17 antagonist to the patient. The invention further provides the use of an IL- 17 antibody in the manufacture of a medicament for treating ankylosing spondylitis (AS), wherein the IL-17 antibody binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Prol26, Ile127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL- 17 antibody has a KD of about 100-200 pM, and wherein the IL-17 antibody has an in vivo half-life of about 4 weeks; and wherein the medicament is for (a) subcutaneous administration to a patient having AS of five doses of about 150 mg - about 300 mg of the IL-17 antibody, each of the five doses being delivered weekly; and (b) thereafter, subcutaneous administration of a dose of about 150 mg - about 300 mg to the patient every month, beginning one month from the fifth subcutaneous dose according to step a). In a further embodiment, the invention provides the use of an IL- 17 antibody in the manufacture of a medicament for treating AS, wherein the IL-17 antibody comprises i) an immunoglobulin VH domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth as SEQ ID NO: 10; ii) an immunoglobulin V domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or iii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and wherein the medicament is for (a) subcutaneous administration to a patient in need thereof five doses of about: (a) 150mg - about 300 mg of the IL-17 antibody, each of the five doses being delivered weekly; and (b) thereafter, subcutaneous M:WillInInDV~it;NKol'DIULLUJA1n,we-LI.OOCX-'/I IlluI4 -3F administration to a patient a dose of about 150 mg - about 300 mg of IL-17 antibody every month. In yet another embodiment, the invention provides the use of secukinumab in the manufacture of a medicament for treating active AS wherein about 150 mg secukinumab is administered by subcutaneous injection to a patient in need thereof, with initial dosing at weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at week 4.

WO 2012/059598 PCT/EP2011/069476 54388 FF Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising: a) assaying a sample from a patient for: i. rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and ii. C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR; and b) thereafter, administering the patient an IL-17 antagonist to the patient if the patient is RF+, ACPA +, or RF+ and ACPA + and the patient has a high level of CRP, a high BSR, or a high level of CRP and a high ESR. Disclosed herein are methods of treating rheumatoid arthritis (RA) comprising administering a therapeutically effective amount of an It 1.7 antagonist to a patient, provided that the patient is selected for treatment on the. basis of: a) being R-F+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high tSlk, or both a high level of CRP and a high ESR, In some embodiments, the step of administering comprises: a) administering the IL- 17 antagonist to the patient during an induction regimen; and b) thereafter administering the IL-17 antagonist to the patient during a maintenance regimen. Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising- a) administering a high risk RA patient three doses of about 10 mg/kg of an IL-17 antagonist, each of the three doses being delivered every other week; and b) thereafter administering about 75 mg - about 150 mg of the IL-17 antagonist to the patient every month, beginning one month from delivery of the third intravenous dose. Disclosed herein are therapeutic regimens for treating rheumatoid arthritis (RA), comprising: a) selecting a patient having RA based on the following criteria; i. the patient is RF+, ACPA+, or both RF+ and ACPA+; and ii. the patient has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR; and b) administering the patient three doses of about 10 mg/kg of an IL-17 antagonist, the first dose being delivered during week zero, the second dose being delivered during.week two, and the third dose being delivered during week four; and c) thereafter administering the patient about 75 mg - about 150 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight. Disclosed herein are methods of determining the likelihood that an RA patient will respond to treatment with an IL- 17 antagonist, comprising assaying a sample from the patient for: a) rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and b) C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR, wherein the patient is likely to respond to treatment of RA with the IL-17 antagonist if the -4- WO 2012/059598 PCT/EP2011/069476 54388 FF patient is RF+, ACPA +, or RF+ and ACPA +; and the patient has a high level of CRP, a high ESR, or a high level of CRP and a high ESR, Disclosed herein are IL- 17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL-I 7 antagonist is to be administered to a high risk RA patient. Disclosed herein are IL-7 antagonists for use in treatingorheumatoid arthritis (RA), characterized in that the [L-17 antagonist is to be administered to a patient selected for treatment on the basis of the patient being a high risk RA patient. Disclosed herein are IL-I7 antagonists for use in treating a high risk RA patient. In some embodiments, the high risk RA patient: a) is seropositive for.rheumatoid factor (RF+), anti citrullinated protein antibody (ACPA+), or both RF+ and ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a high level of CRP and a high ESR. In some embodiments, a high level of CRP is > 10 mg/L, as measured by hsCRP. In some embodiments, a high ESR is.> 28 mm/h. Disclosed herein are IL-17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL-17 antagonist is to be administered to apatient, provided that the patient is selected for treatment on the basis of; a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. Disclosed herein are IL-17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the [[-17 antagonistic to be: a) administered to a high risk RA patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; end b) thereafter administered to the patient as. dose of about 75 mg - about 150mig every month, beginning one month from delivery of the third intravenous dose. Disclosed herein are IL-17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that: a) a sample from a patient is assayed for: i. rheumatoid factor (RF), anti citrullinated protein antibody (ACPA), or RF and ACPA; and ii.C-reactive protein (CRP),.an erythrocyte sedimentation rate (ESR), or both CRP and an ESR; and b) the IL-I 7 antagonist is administered to the patient if the patient is RF+, ACPA +, or RF+ and ACPA + and the patient has a high level of CRP, a high ESR, or a high level of CRP and a high ESR. Disclosed herein are uses of an IL-I7 antagonist for the manufacture of a medicament for treating RA, characterized in that the IL- 17 antagonist is to be administered to high risk RA patient. -5- WO 2012/059598 PCT/EP2011/069476 54388FF Disclosed herein are uses of an IL- 17 antagonist for the manufacture of a medicament for treating RA, characterized in that the IL-17 antagonist is to be administered to high risk RA patient during an induction regimen followed by a maintenance regimen, Disclosed herein are pharmaceutical composition for treating RA, comprising as an active ingredient an IL-17 antagonist, wherein the IL-17 antagonist is to be administered to a high risk RA patient. Disclosed herein are pharmaceutical composition for treating RA, comprising as an active ingredient an IL-17 antagonist, wherein the IL-I7 antagonist is to be administered to a high risk RA patient during-an induction regimen followed by a maintenance regimen. Disclosed herein are therapeutic regimens for treating RA, comprising: a) selecting a high risk RA patient; b) administering about 10 mg/kg of an IL-i 7 antagonist to the patient during weeks 0, 2 and 4; and c) thereafter administering about 75 mg - about 150 mg of the IL-17 antagonist to the patient monthly, beginning week . Disclosed herein are methods of eating a RA patient or a high risk IRA patient, comprising: a) administering an XE17 binding molecule to a patient in need thereof during an induction regimen thatprovides a mean maximum plasma concentration (CsJ of the IL-17 binding molecule of about 360 pg/ml; and b) thereafter administering the IL-17 binding molecule to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL-17 binding molecule between about 8 pg/ml - about 30 pg/ml; and/or ii) a mean AUC tau at steady state of about 331 mg*day/L - about 1323 mg*day/L. Disclosed herein are IL-17 binding molecules for use in treating a RA patient or a high risk RA patient, characterized in that the IL-i7 binding molecule: a) is to be administered to the patient during an induction regimen that provides a mean maximum plasma concentration (C,) of the IL-17 binding molecule of about 360 pg/ml; and b) thereafter, is to be administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 binding molecule between about 8 pg/ml - about 30 pg/mi; and/or ii) a mean AUC tau at steady state of about 331 mg*day/L - about 1323 mg*day/L. Disclosed herein are methods of treating a high risk RA patient, comprising a) administering an IL-I 7 binding molecule to a patient in need thereof during an induction regimen that provides a mean maximum plasma concentration (Cr.n) of the IL- 17 bindingmolecule of about 401 sg/ml; and b) thereafter administering the IL-17 binding molecule to the patient -6- WO 2012/059598 PCT/EP2011/069476 54388 FF during a maintenance regimen that provides: i) an average steady-state trough level of the IL-17 binding molecule of about 9.4 pg/ml - about 31 Ag/ml; and/or ii) a mean AUC tau at steady state of about 314 ng*day/L - about 1256.mg'day/L. Disclosed herein are IL-I 7 binding molecule for use in treating psoriasis, characterized in that the IL-17 binding molecule: a) is to be administered to the patient during an induction regimen that provides a mean maximum plasma concentration (CmaX) of the IL-17 binding molecule of about 401 pg/ml; and b) thereafter, is to be administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 binding molecule of about 9.4 pg/i - about 31 pg/mI;and/or ii) a mean AUC tan at steady state of about 314 mg*day/L - about 1256 mg*day/L. In some embodiments, the maintenance regimen provides an average steady-state trough level of the (L-17 binding molecule of about 9.4 gg/ml - about 17.3 pg/ml, In some embodiments, the maintenance provides an average steady-state trough level of the IL- 17 binding molecule of about 9.4 4g/ml or about 17.3 pg/mL In some embodiments, the induction regimen comprises intravenous administration ofthe IL-17 binding molecule every other week. In some embodiments, the maintenance regimen comprises monthly subcutaneous administration of the IL-17 binding molecule. Disclosed herein are kits comprising: a) a pharmaceutical composition comprising an IL 17 antagonist for use in the treatment of rheumatoid arthritis (RA) in a patient; and b) instructions describing how to administer said pharmaceutical composition to the patient, wherein the patient is characterized as: i) being RF+, ACPA+, or both RF+ and ACPA +; and ii) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. Disclosed herein are IL-17 antagonists in preparation of a medicament for the treatment of RA, provided that the patient is selected for the treatment on the basis of: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. Disclosed herein are IL-17 antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated to comprise containers, each container having a sufficient -7- WO 20121059598 PCT/EP2011/069476 543g8 FF amount of the IL-17 antagonist to allow delivery of at least about 75 mg - about 150 mg [L-17 antagonist per unit dose. Disclosed herein-are IL-17 antagonists for (he manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a highievel of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicamen is formulated to comprise containers, eachtontainer having a sufficient amount of the IL-17 antagonist to allow delivery of at least about 10 mg/kg per unit dose. Disclosed herein are IL-17 antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated at a dosage to allow intravenous delivery of about 10 mg/kg per unit dose. Disclosed herein are IL-17 antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated at a dosage to allow subcutaneous delivery of about 75 mg - about 150 mg IL-i 7 antagonist per unit dose. Disclosed herein are in vitro test methods for selecting a patient for treatment of RA, comprising determining if: i the patient is RF+, ACPA+, or.both RF+ and ACPA+; and ii, the patient has a high level of CRP, a high ESR, or both a high tevel of CRP and a high ESR. In some embodiments of the disclosed in vitro test methods, the patient has an improved therapeutic response to the following regimen: a) administering the patient three doses of about 10 mg/kg of an IL- 17 antagonist, the first dose being delivered during week zero, the second dose being delivered during week two, and the third dose being delivered during week four; and a) thereafter administering the patient about 75 mg - about 150 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight. Disclosed herein are methods for producing a transmittable form of information on a patient having RA, comprising: a) assaying a sample from the patient for: i) rheumatoid factor (RF), ani-citrullinated protein antibody (ACPA), or RF and ACPA; and ii) C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR; and b) embodying the result of step a) in a transmittable form of information. - 8- WO 2012/059598 PCT/EP2011/069476 548 FF Herein are also. provided methods o treating aninlainratory arthritis, co.nprising administering three induction doses (esg., i.v., induction doses) of about 10 mg/kg or several: (e.g., 1, 2, 3, 4, or 5) inductiton doses of about. 150 mg (eg., s.c. induction doses) of an IL-7 antagonist, e.g., IL-1 7 binding molecule (e.g., 1L- 17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) to a patient having an inflammatory arthritis selected from the group consisting of rheumatoid arthritis (RA), spondyloarthropathy,-ankylosing spondylitis (spondylarthritis), and psoriatic arthritis. In some embodiments, the induction doses are delived every other week, and thereafter the patient is administered monthly maintenance doses (e.g,, s.c. maintenance doses) of about 75 mg - about 300 mg (e.g., about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg) of the IL-17 antagonist (e.g.,.secukinumab), e.g., beginning one month from delivery of the final induction dose. Herein are also provided methods of treating RA, comprising selecting a RA patient (e.g., a high risk RA patient) or a patient.having elevated baseline CRP leveLkadministering the patient about 10 mg/kg (e.g, by an iv. rotite) of an1IL-17 atagonistg IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-I 7 receptor binding molecule (e.g., IL-I 7 antibody or antigen binding fragment thereof) every other week (e.g., during week 0, 2 and 4), and thereafter administering the patient about 75 mg - about 300 mg (e.g., about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg) (e.g., by an s.c. route) of the IL-17 antagonist on a monthly basis (e.g., beginning week 8). In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the high risk RA patient: a) is seropositive for rheumatoid factor (RF+), anti citrullinated protein antibody (ACPA+), or both RF+ and ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation-rate (ESR), or both a high level of CRP and a high ESR. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-17 antagonist is an IL- 17 binding molecule or an IL- 17 receptor binding molecule. In some embodiments, the IL-17 binding molecule or an IL-17 receptor binding molecule is an IL-I 7 binding molecule (e.g., IL- 17 antibody) selected from the group consisting of: a) seoukinumab; b) an IL-17 antibody that binds to an epitope of IL-17 comprising Leu?4, Tyr85, HisS6, MetS7, AsnS, Val124, Thr125, Prol26, le127, Val128, His129; c).an IL-17 9 - WO 2012/059598 PCT/EP2011/069476 54388 FF antibody that binds to an epitope of IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80; d) an IL-17 antibody that binds to an epitope of an IL-17 homodimer having two mature:IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, MetS7, Asn88, Val124, Thr1 25, Prol26, Ile127, Val 128, His129. on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain; e) an IL-17 antibody that binds to an epitope of an IL-I homodimer having two mature IL-1 7 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, AsnS8, Val124, Thrl25, Pro126, Ile] 27, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp8O on the other chain, wherein the IL- 17 binding molecule has a K 0 ofabout 100-200 pM, and wherein the IL-l7 binding motecule has-an in vivo-half-life of about-4 weeks; and f) an IL-17 antibody that comprises an antibody selected from thegroup consisting of: i) an immunoglobulin heavy chain variable domain (Va) comprising the amino acid sequence set forth as SEQ ID NO:8; ii) an immunoglobulin light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO: 10; iii) an immunogLobulin Vu domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth as SEQ ID NO: 10; iv) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3; v) an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; vi) an immunoglobulin V, domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO:12 and SEQ ID NO:13; vii) an immunoglobulin Vx domain comprising the hypervariable regions set forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and viii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. In preferred embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-17 binding molecule is a human antibody. In even more preferred embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-1 7 binding molecule is secukinumab. -10- WO 2012/059598 PCT/EP2011/069476 54388 FF BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the study design of the CAIN457F2201 study. Figure 2: A shows ACR20 response last observation carried forward (LOCF) by treatment up to week 16 in study CAIN4571F221 infull analysis set (FAS) B AhowsACR20response (LOCF) by treatment up to week16 in highrisk BA patients-; C shows the ACR2O response over time through week 52 by responders (R) and non-responders (NR) in the FAS. Figure 3: A shows ACR50 response (LOCF) by treatment up to week 16 in study CA1N457F2201 in full analysis set (FAS); B shows the ACR50 response over time through week 52 by responders (R) and non-responders (NR) in the FAS. Figure 4: A shows ACR70 response (LOCF) by treatment up to week 16 in study CA1N457F2201 in full analysis set (FAS); B shows the ACR70 response over time through week 52 by responders (R) and non-responders (NR) in the PAS. Figure 5: A shows DAS28-CRP change from baseline (LOCF) by treatment up to week 16 in study CAIN457F2201 FAS; B shows the DAS28-CRP response over time through week 52 by responders (R) and non-responders (NR) in the FAS. Figure 6: A shows HAQC scores change from baseline (LOCF) by treatment up to week 16 in study CAJN457F2201 PAS; B shows the HAQC response over time through week 52 by responders (R) and non-responders (NR):in the FAS. Figure 7 shows the ACR20/50/70 response at week 52 by responders (R) and non-responders (NR) in the FAS. Figure 8: A shows the A CR20/50/70 % response at week 16 in the high risk RA patients and non-high risk RA patients. B shows the DAS28-CRP response at week 16 in the high risk RA patients and non high risk RA patients. Figure 9 shows ACR20 responder rates by dose group and CRP baseline levels in CAIN457F220I study. Columns represent, from the left to the right, all patients, patients with a CRP baseline greater than 10 mg/L, greater than 20 mg/L, and greater than 30 mg/L, respectively. Figure 10 shows simulated secukinumab pharmacokinetics (PK) in rheumatoid arthritis patients. The full line shows PK without an induction strategy (one dose of 300 mg s.c. at Week 0), dotted line shows PK with a subcutaneous induction strategy (300 mg s.c. at Weeks 0, 1, 2, 3 and 4) and dashed line shows PK with an intravenous induction strategy (10 mg/kg i v. at Weeks 0, 2 and 4). Each of the three options is followed by 300 mg s.c. every 4 weeks for maintenance. - 11 - WO 2012/059598 PCT/EP2011/069476 5438:8 FF DETAILED DESCRIPTION OF THED1SCIOSUI RE The 1987 American College of Rheumnatology (ACR) classifiation diteria for RA discriminates patients with established RA from individuals with a combination of other definite rheumatological diagnoses. These criteria were not helpful in identifying patients with early RA disease who might benefit from early intervention. In 2010 ACR provided a new classification system that focuses on RA features at earlier stages of disease that are associated with persistent and/or erosive disease (hereinafter "2010 ACR/EULAR" criteria), Aletaha et al. (2010) Ann. Rheum. Dis. 69:1580-1588. The 2010 ACR/EULAR classification system focuses on six criteria; the first two criteria define who should be tested for RA., while the remaining four criteria are scored (Table 1). A score of six or greater is indicative of definite RA. Table 1; The 2010 American College of Riteumatology/European League Against Rheumatism ScoIre i classification Criteria for Rheumatoid Arthritis (RA) Target population (Who should be tested?): Patients who 1) have at least I joint with definite clinical synovitis (swelling)* 2) with the: synovitis not better explained by anotherdiseaset Classification criteria for RA (score-based algorithm: addscore of categories A-); a score of2a6/10 is needed for classficatidon of a patient as having definite RA)% A. Joint involvement I large joint 0 2-10 large joints I 1-3 small joints (with or without involvement of largejoints)# 2 4-10 small joints (with or without involvement of large joints) 3' >10joints (at least I small joint)** 5 B. Serology (at least I test result is needed fbr classification)tt Negative RF and negative ACPA 0 Low-positive RF or low-positive ACPA 2 I High-positive RF or high-positive ACPA 3 C. Acute-phase reactants (at least I test result is needed for classification)$ Normal CRP and normal ESR 0 Abnormal CRP or abnormal ESR D. Duration of syMptoms§§ <0 weeks -12- WO 2012/059598 PCT/EP2011/069476 54388 FF >6 weeks * The criteria are aimed at classification of newly presenting patients. In addition, patients with erosive disease typical of rheumatoid arthritis (RA) with .a history compatible with prior flfillment of the'2010 criteria should be classified as having RA. Patient's with longstanding disease, including those whose disease is inactive (with or without treatment) who, based on retrospectively available data, have previously fulfifled the 2010 criteria should be classi fled as having RA. t Differential diagnoses vary among patients with different presentations, but may include conditions such as systemic lupus erythematosus, psoriatic arthritis, and gout. If it is unclear about the relevant differential diagnoses to consider, an expert rheumatologist should be consulted. $ Although patients with a score of <6/10 are-not classifiable as having RA, their status can be reassessed and the criteria might be fulfilled cumulatively over time, § Joint involvement refers to any swollen or tenderjoint onexamination, which may be confirmed by imaging evidence of synovitis.. Distal interphalangea joints, first aromnetacarpal and first ietatarsophalangealjbints are excluded from assessment; Categories ofjoint distribution arer classified according to the location and number of involved joints, with placementinrto the highest cetegory possiblbased of the pattern ofjoint involvement. T "Large joints" refers to shoulders, elbows, hips; knees, and ankles # "Small joints" refers to the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangea] joints, and wrists. ** In this category, at least I of the involved joints must be a small joint; the other joints can include any combination of large and additional small joints, as well as other joints not specifically listed elsewhere (e.g., temporomandibular, acromioclavicular, sternoclavicular, etc.). it Negative refers to I U values that are less than or equal to the upper limit of nonnal (ULN) for the laboratory and assay; low-positive refers to IU values that are higher than the ULN but </=3 times the ULN for the. laboratory and assay;. high-positive refers to IU values that are >3 times the ULN for the laboratory and assay. Where rheumatoid factor (RF) information is only available as positive or negative, a positive result should be scored as low-positive for RF. ACPA - anti-citrullinated protein antibody. tg Normal/abnormal is determined by local laboratory standards. CRP = C-reactive protein; ESR =erythrocyte sedimentation rate. §§ Duration of symptoms refers to patient self-report of the duration of signs or symptoms ofsynovitis (e.g., pain, swelling, tenderness) ofjoints that are clinically involved at the time of assessment, regardless of treatment status. In searching for indicators predictive of an RA patient's response to treatment with an IL 17 binding molecule, e.g., an IL t -7antibody such as secukinurinb, we have analyzed two of the four 20 10 ACR/EULAR scoreable criteria to determine whether these criteria influence response to treatment with an IL-1 7 binding molecule, such as secukinumab, First, we analyzed patient serology to determine whether the patient is RF + and/or ACPA +. Second, we analyzed the presence of acute-phase reactants to determine whether the patient has a high level of C-reactive - 13- WO 2012/059598 PCTIEP2011/069476 543g8 FF protein (CRP) and/or a high erythrocyte sedimentation rate (ESR). In the process, we discovered that patients; 1) that are RF + or ACPA. + (or both); and 2) who have a. high level of CRP or ESR (or both) are more likely to have a good response to treatment with an IL-i7 binding molecule, e.g., an IL-1 7 antibody, such as secukinumab, Such patients (termed herein "high risk RA patients") are those with the most salient features of RA.(See, e.g., Yildirim etal. (2004) Annals Clin. Lab. Scid 4:423). Accordingly, disclosed herein are methods of treating rheumatoid arthritis (RA), comprising administering a therapeutically-efdetive amount of an IL-I 7 binding molecule to a high risk RAjpatieit. We have additionally determined that elevated baseline CRP levels (e.g., > about 10 mg/L) are also associated with responsiveness to secukinumab. Accordingly, disclosed herein are methods of treating rheumatoid arthritis (RA), comprising administering a therapeutically effective amount of an IL-17 binding molecule to a RA patient displaying elevated baseline CRP levels (e.g., greater than about 10 mg/L, greater than about 20 mg/L, greater than about30 mg/L). We have further discovered that the treatment regimens useful in treating high risk RA patients are additionally useful in treating RA in non-high risk patients and patients having other inflammatory arthritis, e.g., ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Accordingly, disclosed herein are dosing and treatment regimens for addressing inflammatory arthridities (e.g., RA, AS, PsA), comprising administering a therapeutically effective amount of an IL-17 binding molecule to a patient having an inflammatory arthridities. The term "comprising" encompasses "including" as well as "consisting," esg. a composition "comprising" X may consist exclusively of X or may include something additional, e.g.,X + Y. The term "about" in relation to a numerical value x means +/-10% unless the cotext dictates otherwise. The term "about," when used in reference to a pharmacokinetic (PK) parameter (e.g., AUC, C., tmox, trough levels, etc.), indicates a treatment (e.g., dosage and/or dosing regimen) that a skilled artisan would consider bioequivalent to a reference treatment. For bioequivalence, the standard method to show bioequivalence is to prove statistically that the ratio of a given PK parameter (e.g., AUC, C.) between two treatments (i.e., a reference treatment and a test treatment) is between 0.8 - 1,25, which is shown by means of a 90% confidence interval (Cl) around the ratio (the lower limit of this C1 being above 0.8, and the upper limit of -14- WO 2012/059598 PCT/EP2011/069476 54388 FF this C1 being below 1.25). Thus; egg., if during a. trial comparing the PKiprofiles of a reference treatment and a test treatment, a reference CM, of 10 pg/ml.is obtained, then the test treatment will be considered "about 10 pg/ml" if a skilled artisan would consider the test treatment to be bioequivalent. As used herein, pharmacokinetic terms, eg., t, t 1 2, AUC, AUC(o.

1 ,) (AUC to the end of a given dosing period, hereinafter "AUC tau"X C,,, have their art-accepted meanings. The term "administering" in relation to a compound, e.g., an IL-17 binding molecule or an anti-rheumatic agent, is used to refer to delivery of that compound by any route. The phrase "active rheumatoid arthritis" or "active RA" is used to mean RA with visible signs and symptoms (e.g., swelling, difficulty in flexion, etc.). The term "assaying" is used to refer to the act of detecting, identifying, screening, or determining, which act may be performed. by any conventional means. For example, a sample may be assayed for the presence of a particular marker by using an ELISA assay, a Northern blot, imaging, etc. to detect whether that marker is present in the sample. The word "substantially" does not exclude "completely," eg., a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted front the definition of the. disclosure. As used herein, "mg/kg" refers to mg of drug per kg body weight of the patient being administered the drug. "IL-17 antagonist" as used herein refers to a molecule capable of antagonizing (e.g., reducing, inhibiting, decreasing, blocking, delaying) IL-17 function, expression and/or signalling (e.g., by blocking the binding of IL-17 to the IL-17 receptor). Non-limiting examples of IL-17 antagonists include IL-17 binding molecules and IL-17 receptor binding molecules. In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, an IL 17 antagonist is employed. By "IL-17 binding molecule" is meant any molecule capable of binding to the human IL 17 antigen either alone or as it is associated with other molecules. The binding reaction may be shown by standard methods (qualitative assays) including, for example, a binding assay, competition assay or a bioassay for determining the inhibition of IL-1 7 binding to its receptor or any kind of binding assays, with reference to a negative control test in which an antibody of unrelated specificity but of the same isotype, e.g. an anti-CD25 antibody, is used. Non-limiting examples of IL-1' binding molecules include small molecules, IL-17 receptor decoys, and - 15 - WO 2012/059598 PCT/EP2011/069476 5438 FF antibodies as produced by B-cells or hybridomas and chimeric, CDR-grafted or human antibodies or any fragment thereof, e.g., F(ab')2 and Fab fragments, as well as single chain or single domain antibodies. Preferably the IL-17 binding molecule antagonizes (e.g., reduces, inhibits, decreases, delays) IL-17 function, expression and/or signalling. In some embodiments of the disclosed methods, regimens,. kits, processes, uses and compositions, an IL-17 binding molecule is employed. By "IL-17 receptor binding molecule" is meant any molecule capable of binding to the human IL-17 receptor either alone or associated with.other molecules. The binding reaction may be shown by standard methods (qualitative assays) including, for example, a binding assay, competition assay or a bioassay for determining the inhibition of IL-17 receptor binding to IL-7 or any kind of binding assays, with reference to: a negative control test in which an antibody of unrelated specificity but of-the same isotype, ekg. an anti-CD25 antibody, is used. Non-imiting examples of IL-17 receptor binding molecules include small molecules, IL-17 decoys, and antibodies to the fL-17 receptor as produced by B-cells or hybridomas and chimeric, CDR grafted or human antibodies or any fragment thereof, e.g., F(ab') 2 and Fab fragments, as well as single chain or single domain antibodies. Preferably the IL-17 receptor binding molecule antagonizes (e.g., reduces, inhibits, decreases, delays) IL-17 function, expression and/or signalling, In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, an IL-17 receptor binding molecule is employed. The term "antibody" as referred to herein includes whole antibodies and any antigen binding portion or single chains thereof, A naturally occurring antibody is a glycoprotein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CHlI, CH2 and -CHi. Each light chain is comprised of a light chain variable region (abbreviated hetein as VL) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The Vws and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR), Each VH and VL is composed of three CDRs and four FRs arranged from amino-terminus to carboxy-terminus in the following order: FRI, CDR], FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains -16- WO 2012/059598 PCT/EP2011/069476 54388 FF contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system. In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, an antibody to IL-1 7 or theIL-17 receptor is employed. The term "antigen-binding portion" of anantibody as uted heiein, refers to fragnients of an antibody that retain theability to specifically bind to an antigern (e~go, IL-17). It has been shown that the antigen-binding function of an antibody can be performed by fragments of a full-length antibody. Examples of binding fragments encompassed within the term "antigen-binding portion" of an antibody include a Fab fragment, a monovalent fragment consisting of the VL, V, CL and CH I domains; a. F(ab)2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region; a Fd fragment consisting of the Vq and CHI domains; a Fv fragment consisting of the V 1 , and VH domains of a single arm of an antibody; a dAb fragment (Ward et al., 1989 Nature 341:544-546), which consists of a VH domain; and an isolated complementarity determining region (CDR). Exemplary antigen binding sites include the CDRs of secukinumab as set forth in SEQ ID NOs:1-6 and 11-13 (Table 4), preferably the heavy chain CDR3. Furthermore, although the two domains of the Fv fragment, VL and VH, are coded for by separate genes, they can be joined, using recombinant methods, by a synthetic tinker that enables them to be made as a single protein chain in which the VL and VH regions pair to form monovalent molecules (known as single chain Fv (scFv); see, e.g., Bird et al., 1988 Science 242:423-426; and Huston etal, 1988 Proc. Nat. Acad. Sc. 85:5879-5g83). Such single chain antibodies are also intended to be encompassed within the term ,antibody". Single chain antibodies and antigen-binding portions are obtained using conventional -techniques known to those of skill in the art. In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, a single chain antibody or an antigen-binding portion of an antibody against IL-17 (e.g., secukinumab) or the IL-17 receptor is employed. The term pharmaceuticallyy acceptable" means a nontoxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). An "isolated antibody", as used herein, refers to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds IL-1 7 is substantially free of antibodies that specifically bind antigens other -17- WO 2012/059598 PCT/EP2011/069476 5438.8 FF than [L-17). An isolated antibody may be substantially free of other cellular material and/or chemicals, An isolated antibody that "specifically binds" IL- 17 may however, be -cross-reactive with other antigens, such as IL- 7 molecules fraon other species. In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, the IL-17 antagonist is an isolated antibody. The terms "monoclonal antibody" or "monoclonal antibody composition" as used herein refer to a preparation of antibody molecules of single molecular composition. A monoclonal antibody composition displays a single binding specificity and affinity for a particular epitope. In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions. the IL-17 antagonist is a monoclonal antibody. The term "human antibody", as used herein, is intended to include antibodies having variable regions in which both the framework and CDR regions are derived from sequences of human origin. Furthermore, if the antibody contains a constant region, the constant region also is derived from such human sequences, e.g., human germline sequences, or mutated versions of human gernline sequences or antibody containing: consensus framework sequences derived from human framework sequences analysis as -described in Knappik, et at. (2000 3 Mol Biol .296, 57 86). A "human antibody" need not be produced by a human, human tissue or human cell. The human antibodies of the disclosure may include amino acid residues not encoded by human sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo). However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences, In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, the IL 17 antagonist is a human antibody. The term "IL-IT' refers to IL-1 7A, formerly known as CTLA8, and includes wild-type IL 17A from various species (e.g., human, mouse, and monkey), polymorphic variants of IL-I 7A, and functional equivalents of IL-17A. Functional equivalents of IL-17A according to the present disclosure preferably have at least about 65%, 75%, 85%, 95%, 96%, 97%, 98%, or even 99% overall sequence identity with a wild-type IL-17A (e.g., human IL-17A), and substantially retain the ability to induce IL-6 production by human dermal fibroblasts. - 18 - WO 2012/059598 PCT/EP2011/069476 54388 FF The term "Ko" is intended to refer to the dissociation constant, which is obtained fiom the ratio of Kj to K. (i.e. K 4

/K

1 ) and is expressed as a molar concentration (M). KD values for antibodies can be determined using methods well established in the art. A niethod for determining the K 0 of an antibody is by using surface plasmon resonance, or using a biosensor system such as a Biacore@ system. In some embodiments of the invention the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) binds human IL-17 with a KDOf about 100-250 pM. As used herein, the term "affinity" refers to the strength of interaction between antibody and antigen at single antigenic sites. Within each antigenic site, the variable region of the antibody "arm" interactsThrough weak non-covalent forces with antigen at numerous sites; the more interactions, the stronger the affinity. Standard assays to evaluate the binding affinity of the antibodies toward IL- 17 of vadous species are known in the art, including for example, ELISAs, western blots and RIAs. The binding kinetics (e.g., binding affinity) of the antibodies also can be assessed by standard assays known in the art, such as by Biacore analysis. Assays to evaluate the effects of the antibodies on functional properties of IL-17 (e.g., receptor binding, preventing or ameliorating osteolysis) are described in further detail in the Examples. As used herein, the term "subject" and "patient" includes any human or nonhuman animal. The term "nonhuman animal" includes all vertebrates, e~g., mammals and non-mammals, such as nonhuman primates, sheep, dogs, cats, horses, cows chickens, amphibians, reptiles, etc. An antibody that "inhibits" one or more of IL-17 functional properties (e.g., biochemical, immunochemical, cellular, physiological or other biological activities, or the like) as determined according to methodologies known to the art and described herein, will be understood to relate to a statistically significant decrease in the particular activity relative to that seen in the absence of the antibody (or when a control antibody of irrelevant specificity is present). An antibody that inhibits IL-17 activity affects a statistically significant decrease, e.g., by at least 10% of the measured parameter, by at least 50%, 80%.or 90%, and in certain embodiments an antibody of the disclosure may inhibit greater than 95%, 98% or 99% of IL-17 functional activity. The term "derivative", unless otherwise indicated, is used to define amino acid sequence variants, and covalent modifications of an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor -19- WO 2012/059598 PCT/EP2011/069476 54388 FF binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) according to the present disclosure, e.g., of a specified sequence. A "functional derivative" includes a molecule having a qualitative biological activity in common with the disclosed tL-17 antagonista, e.g IL 17 binding molecules (e.g., IL- 17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e.g., IL-17 antibody or antigen binding fragment thereof). A functional derivative includes fragments and peptide analogs of an IL-17 antagonist as disclosed herein. Fragments comprise regions within the sequence of a polypeptide according to the present disclosure, e.g., of a specified sequence. Functional derivatives of the IL-17 antagonists disclosed herein preferably comprise Vx and/or VL domains that have at least about 65%, 75%, 85%, 95%, 96%, 97%, 98%, or even 99% overall sequence identity with the Vr and/or VL sequences of the iL47 binding moleclesi'stsed herein (e.g., the VH and/or VL sequences of Table 4), or comprise.CDRs that have at leastmabout65%, 75%, 85%;95%, 960/, 97%, 98%, or even 99% overall sequence identity with thetDRs of the IL-47 antagonists (e.g., secukinumab) disclosed herein (e,g., have 1, 2, or 3 amino acid differences from the CDRs set forth in Table 4), and substantially retain the ability to bind the human IL-17 or, e g., inhibit IL-6 production of I L-17 induced human dermal fibroblasts. "Inhibit IL-16" as used herein refers to the ability of an IL-17 antagonist (e.g., secukinumab) to decrease IL-6 production from primary human dermal fibroblasts. The production of IL-6 in primary human (dermal) fibroblasts is dependent on IL-17 (Hwang SY et al., (2004) Arthritis Res Ther; 6:R120-128. In short, human dermal fibroblasts are stimulated with recombinant IL-17 in the presence of various concentrations of an IL-17 binding molecule or human IL- 17 receptor with Fc part. The chimeric anti-CD25 antibody Simulect" (basiliximab) may be convienently used as a negative control. Supernatant is taken after 16 h stimulation and assayed for IL-6 by ELISA. An IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e;g., secukinumab) or IL-l7 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) as disclosed herein typically has an lCso for inhibition of 1L6 production (in the presence I nM human IL-147) of about 50 nM or less (e.g., from about 0.01 to about 50 nM) when tested as above, i.e., said inhibitory activity being measured on IL-6 production induced by hu-IL-I7 in human dermal fibroblasts, In some embodiments of the disclosed methods, regimens, kits, processes, uses and compositions, IL- 17 antagonists, e.g., IL-I 7 binding molecules (e.g., IL-1 7 antibody or antigen - 20 - WO 2012/059598 PCT/EP2011/069476 54388 FF binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e g., IL-17 antibody or antigen binding fragment thereof) and functional derivatives thereof have an ICso for inhibition of IL-6 production as defined above of about 20 nM or less, more preferably of about 10 nM or less, more preferably ofabout$nM or less,- more preferably of about 2 nM or less, more preferably ofabout nM orless. The term covalentt modification" inoludes modifications of a polypeptide according to the present disclosure, e.g., of a specified sequence; or a fragment thereof with an organic proteinaceous or non-proteinaceous derivatizing agent, fusions to heterologous polypeptide sequences, and post-translational modifications. Covalent modified polypeptides, e.g., of a specified sequence, still have the ability to bind the human IL-17 or, e.g., inhibit IL-6 production of IL- 17 induced human dermal fibroblasts by crosslinking; Covalent modifications are traditionally introduced by reacting targeted amino acid residues with an organic derivatizing agent that is capable of reacting with-selected sides or terminal residues, or by harnessing mechanisms of post-translational modifications that function in selected recombinant host cells. Certain post-translational modifications are the result of the action of recombinant host cells on the expressed polypeptide. Glutaminyl and asparaginyl residues are frequently post translationally deamidated to the corresponding glutamyl and aspartyl residues; Alternatively, these residues are deaminated under mildly acidic conditions. Other post-translational modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl, tyrosine or threonyl residues, methylation of the a-amino groups of lysine, arginine, and histidine side chains, see, e.g., T. E. Creighton,.Proteins: Structure and Molecular Properties, W. H. Freeman & Co., San Francisco, pp. 79-86 (1983), Covalent modifications, e.g., include fusion proteins comprising a polypeptide according to the present disclosure, e.g., of a specified sequence and their amino acid sequence variants, such as immunoadhesins, and N-terminal fusions to heterologous signal sequences. The phrase "substantially identical" means that the relevant amino acid or nucleotide sequence (e.g., CDR(s), VH, or VL domain) will be identical to or have insubstantial differences (e.g., through conserved amino acid substitutions) in comparison to a particular reference sequence. Insubstantial differences include minor amino acid changes, such as I or 2 substitutions in a 5 amino acid sequence of a specified region. In the case of antibodies, the substituted antibody has the same specificity and has at least 50% of the affinity of the same. -21- WO 2012/059598 PCT/EP2011/069476 54388 FF Sequences substantially identical (e.g, ateastabdut 85% sequence identity) to the sequences disclosed herein are also part ofthis applicaion.. In saoMeembodiments, the sequence identity can be about 90% or greater, e~g., 90%, 91%, 92%, 93%, 94% 95%, 96%, 97%, 98%, 99% or higher. "Identity" with respect to a native polypeptide and its functional derivative is defined herein as the percentage of amino acid residues in the candidate sequence that are identical with the residues of a corresponding native polypeptide, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent identity, and not considering any conservative substitutions as part of the sequence identity. Neither N- or C-terminal extensions nor insertions shall be construed as reducing identity. Methods and computer programs for the alignment are well known. The percent identity can be determined by standard alignment algorithms, for example, the Basic Local Alignment Search Tool (BLAST) described by Altshul et al ((1990) , Mol. Bio]., 215: 403 410); the algorithm of Needleman et al. ((1970) J. Mol. Biot,, 48: 444 453); or the algorithm of Meyers et al. ((1988) Comput. AppL. Biosci., 4: 11 17). A set of parameters may be the Blosum 62 scoring matrix with a gap penalty of 12, a gap extend penalty-of 4, and a frameshift gap penalty of 5. The percentidentitybetween two amino acid or nucleotide sequences can also be determined using:the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. "Amino acid(s)" refer to all naturally occurring L-a-amino acids, e.g., and include D amino acids. The amino acids are identified by either the well known single-letter or three-letter designations. The term "amino acid sequence variant" refers to molecules with some differences in their amino acid sequences as compared to the sequences according to the present disclosure. Amino acid sequence variants of a polypeptide according to the present disclosure, e.g, of a specified sequence, still have the ability to bind the human IL-1 7 or, e.g., inhibit IL-6 production of IL-1 7 induced human dermal fibroblasts. Substitutional variants are those that have at least one amino acid residue removed and a different amino acid inserted in its place at the same position in a polypeptide according to the present disclosure, e.g., of a specified sequence, These substitutions may be single, where only one amino acid in the molecule has been substituted, or they may be multiple, where two or more amino acids. have been substituted in the same molecule. Insertional -22 - WO 2012/059598 PCT/EP2011/069476 S4388 FF variants are those with one or more amino acids inserted immediately adjacent to an amino acid at a particular position in a polypeptide according to the-present disclosure, e.g., of a specified sequence. Immediately adjacent to an amino acid means connected to either the a-carboxy or a amino functional group of the amino acid. Deletional variants are those with one or more amino acids in a polypeptide according to the present disclosure, e.g., of a specified sequence, removed. Ordinarily, deletional variants will have one or two amino acids deleted in a particular region of the molecule. As used herein, a "therapeutically effective amount" refers to an amount of an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g. IL-17 antibody or antigen binding fragment thereof) that is effective upon single o multiple dose administration to a subject (such as a human patient) ttrating peenting.preventing the onst of, curing, delaying, reducing the severity of, ameliorating-afleast one symptom of a disorder or recurring disorder, or prolonging the survival of the subject beyond that-expected in the absence of such treatment. When applied to an individual active ingredient (e.g., an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-1 7 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof)) administered alone, the term refers to that ingredient alone. When applied to a combination, the term refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously. The terms "treatment" or "treat" refer to both prophylactic or preventative treatment as well as curative or disease modifying treatment, including treatment of patient at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition, and includes suppression of clinical relapse. The treatment may be administered to a subject having a medical disorder or who ultimately may acquire the disorder, in order to prevent, cure, delay the onset of, reduce the severity of, or ameliorate one-or more symptoms of a disorder or recurring disorder, or in order to prolong the survivalof a subject beyond that expected in the absence of such treatment. As used herein, the phrase "inflammatory arthritis" refers to a variety of conditions of the joints that involve the immune system and inflammation, and includes autoimmune disorders, - 23 - WO 2012/059598 PCT/EP2011/069476 54388 FF e.g., rhuematoid arthritis. Non-limiting examples include seronegative spondyloatthropathies such as AS, Reiter's syndrome, PsA,-enteropathic arthrits, and other arthropathies such as RA, juvenile rheumatoid arthritis and systemic onset rheumatoid arthritis, crystaline arthritis (gout pseudogout, apatite gout), polymyalgia rheurnatica, amyloid arthritis, pigment villonodular synovitis, synovial chondromatosis, hemophilic arthritis, and reactive synovitis. In soee embodiments of the disclosed methods, tegirnens, uses, kits, and pharmaceutical compositions, the patient has an inflammatory arthridities. As used herein, the phrases ankylosingg spondylitik ' "AS', and "spodyioafthropathy" refer to inflammatory arthridities characterized by chronic inflammation ofjoints, which can include the spine and the sacroillum in the pelvis, and which can cause eventual fusion of the spine. The modified New York criteria for AS or the ASAS axial SPA criteria (2009) may be used to diagnose a patient as having AS. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has AS. As used herein, the phrase "psoriatic arthritis" and "PsA" refer to an inflammatory arthridities that is often associated with psoriasis of the skin. A variety of criteria, e g, Moll and Wright criteria, Modified ESSG criteria,.McGonagle criteria, the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, etc. may be used to diagnose a patient as having PsA. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has PsA. As used herein, "rheumatoid arthritis" or "RA" refers to a chronic, systemic inflammatory arthridities that may affect many tissues -and organs, but principally attacks synovial joints. The 2010 ACR/EULAR criteria may be used to diagnose a patient as having RA. In some embodiments of the disclosed methods, regimensb uses, kits, and pharmaceutical compositions, the patient has RA. As used herein, the phrase "2010 ACRIEULAR criteria" refers to the .2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA found in Aletaha et al, (2010) Ann. Rheum. Dis. 69:1580-1588. That criteria, which is used to classify a patient as having rheumatoid. arthritis, is set forth in Table 1. As used herein, "C-reactive protein" and "CRP" refers to serum C-reactive protein, a plasma protein commonly used as an indicator of the acute phase response to inflammation, The level of CRP in plasma may be given in any concentration, e.g., mg/dl, nmol/L. Levels of CRP - 24 - WO 2012/059598 PCTIEP2011/069476 54388 FF may be measured by a variety of well known methods, e.g.,:radial imnunodifkusion, electroimmunoassay, intmunoturbidimetry, ELISA, tUrbidimetric methods, fluorescence polarization immunoassay, and laser nephelometry. Testing for CRP may employ a standard CRP test or a high sensitivity CRP (hs-CRP) test (ie, a high sensitivity test that is capable of measuring low levels of CRP in a sample using laser nephelometry). Kits for detecting levels of CRP may be purchased from various companies, e.g., Calbiotech, [no, Cayman Chemical, Roche Diagnostics Corporation, Abazyme, DADE Behring, Abnova Corporation, Aniara Corporation, Bio-Quant Inc., Siemens Healthcare. Diagnostics, etc. As used herein "high level of CRP" refers to an above-normal CRP level as defined inthe 2010 ACR/EULA R criteria (Aletaha et al. (2010) Ann. Rheum. Dis. 69:1580-88). According:.to the 2010 ACR/EULAR criteria; normal I abnormal CRP is based on local laboratory standards. Each local laboratory will employ a cutoff value for abnormal (high) CRP based on that laboratory's rule for calculating normal maximum CRP. A physician generally orders a CRP test from a local laboratory, and the local laboratory reports normal or abnormal (low or high) CRP using the rule that particular laboratory employs to calculate normal CRP. Thus, unless the context dictates otherwise, as usedsherein "high level ofCRP?" is not meant to denote a particular numerical value, as what is considered a normal CRP value will differ between laboratories and assays. In some embodiments of the disclosure, a "high level of CRP" is > about 10 mg/L (e.g., 10 mg/L), > about 20 mg/L (e.g., 20 mg/L) or > about 30 mg/L (e.g., 30 mg/L). The CRP level, when assessed at baseline, is referred to as "baseline CRP". A high level of CRP at baseline may be referred to as "elevated baseline CRP" or "high baseline CRP". In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has a high baseline CRP (or hsCRP) or a high level of CRP (or hsCRP). The term "hsCRP" refers to the level of CRP in the blood as measured by high sensitivity CRP testing. As used herein, erythrocytee sedimentation rate", "ESR", "sedimentation rate", and "sedrate" refer to the rate of sedimentation of erythrocytes in a patient sample (e.g., plasma sample). An ESR reflects plasma viscosity and the presence of acute phase proteins, and is normally reported in "mm/hr". ESR is performed by measuring the distance that red blood cells precipitate in a tube over time. Typical ESR testing methods utilize the Westergren test, the Zeta Sedimentation Rate (ZSR) test and the Wintrobe test. (See, Moseley and Bull (1982) Clin. Lab Haematol. 4:169-78; Miller et a. (1983) Br Med J (Clit Res Ed) 286 (6361):266, Wetteland Pet -25- WO 2012/059598 PCT/EPZOI1/069476 54388 FF a], (1996) .Intern. Med. 240 (3): 125-310, all of which.are incorporated by reference herein in their entirety). Commercial kits for measuring ESR are available from, e.g., ARKRAY USA, BD Diagnostic Systems, and Polymedco Inc. ESR instruments may be found, e.g; in US Patent 6974701, and from various companies, such as Steellex Scientific, Nicesound Electronics Co., Globe Scientific Inc., Alifax, Analysislnstrument AB, Streck Laboratories, PolyMed Co, Inc., and Quantimetrix, As used herein "high ESR" refers to an above normal ESR as defined in the 2010 ACR/EULAR criteria (Aletaha et al. (2010) Ann. Rheum. Dis. 69:1580-88). According to the 2010 ACRIEULAR criteria, normal / abnormal ESR is based on local laboratory standards. Each local laboratory will employ a cutoff value for-abnormal (high) ESR based on that laboratory's rule for calculating normal maximum BSR. A physician generally orders an ESR test from a local laboratory, and the local laboratory will report normal or high ESR using the rule that laboratory employs to calculate normal ESR. Thus, unless the context dictates otherwise, as used herein "high ESR" is not meant to denote a particular numerical value, as what is considered a normal ESR value will differ between laboratories and assays. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has a high ESR. As used herein, "rheumatoid factor" or "RF" refers to autoanti bodies against the Fc portion of IgG antibodies, which are often present in RA patients. As used herein "RF" includes any RF isotype, e.g., IgG, IgE, IgM and IgA. RF can be assayed using a variety of well-known techniques that are available to determine the presence or absence of a particular antibody, e.g., an ELISA assay, an agglutination test, a nephelometry test, etc. RF levels may be reported by laboratories in a variety of ways e.g., IU/ml, units/ml, and titer (using a dilution test to measure how much a blood.sample from a patient may be diluted before RF can no longer he detected, e.gi, a titer of 1:80 indicates more detectable RF than a titer of 1:20). RF kits are commercially available, e..g., from IBL -America.(Immuno-Biological Laboratories). A patient that is seropositive for RF is referred to herein as "RF". Similarly, if a sample from a patient has RF, then that sample is "RF+". Each local laboratory will employ a cutoff value for normal RF levels based on that laboratory's rule for calculating normal maximum RF. As suggested by Aletaha et al. (2010) Ann. Rheum. Dis. 69:1580-1588, a patient will be considered RF+ based on the upper limit of normal [ULN] for the respective laboratory test and - 26 - WO 2012/059598 PCT/EP2011/069476 54388 FF assay; a patient is RF+ if a value greater than the ULN for the respective laboratory test and assay is determined. Accordingly, unless the context dictates otherwise, as used herein "RF+" is not meant to denote a particular numerical value, as the ULN will differ between laboratories and assays. As a non-limiting example, at the time of testing, Laboratory X gives the normal range of RF in the blood as 14 - 60 units/mL. At theitime of testing, Laboratory Y gives the normal range of RF in the blood as <40lU/mh. At the time oftesting, Laboratory Z gives the-normal range of RF in the blood as 1:20 to 1:80 titer. Thus, apatient would be R-+ if Laboratory X returned an RF level of greater than 60 units/ml, if Laboratory Y returned an RF value of breather than 40 IU/m[, or if Laboratory Z returned an RF titer greater than 1:80. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient is RF+. The term "seropositive" used to mean the presence of a specific substance (e.g. RE) in a patient's blood serum. As used herein, "anti-citrullinated protein antibody", "ACPA", "anti-cyclic citrullinated peptide antibody" and "anti-CCP" refers to autoantibodies that bind citrulfinated amino acid residues on proteins, which are found in the joints of in RA patients, Cyclic citrullinated peptides are used in in vitro tests (e.g., ELISA assays) to determine the presence of ACPA in a patient's blood; as a result, an ACPA is also referred to as an "anti-CCP" antibody. ACPA levels can be assayed using a variety of well-known techniques that are available to determine the presence or absence of a particular antibody, eg., agglutination, ELISA assay, etc. ACPA kits are commercially available, e.g., the DIASTAT® anti-CCPtest from Axis-Shield Diagnostics, Ltd. (UK) and AxsYM Anti-CCP6 kit from Abbot Diagnonstics (Germany). A patient that is seropositive for ACPA is referred to herein as "ACPA+". Similarly, if a sample from a patient has ACPA, then that sample is "ACPA+". Each local laboratory will employ a cutoff value for normal ACPA levels based on that laboratory's rule for calculating normal maximum ACPA. As suggested by Aletaha et al. (2010) Ann. Rheun. Dis. 69:1580 1588, a patient will be considered ACPA+ based on the upper limit of normal [ULN] for the respective laboratory test and assay; a patient is ACPA+ if a value greater than the ULN for the respective laboratory test and assay is determined. Accordingly, unless the context dictates otherwise, as used herein "ACPA+" is not meant to denote a particular numerical value, as the ULN will differ between laboratories and assays. As a non-limiting, at the time of testing, - 27 - WO 2012/059598 PCT/EP2011/069476 54388 FF Laboratory A gives the reference range ofACPA in the blood as <20 EU (arbitrary ELISA units). At the time of testing, Laboratory B gives the reference range of ACPA in the blood as < 5 U/ml. Thus, apatient would beACPA+ if Laboratory A returned an ACPA value greater than 20 EU or if Laboratory B returned an ACPA value of greater than 5 U/ml. In some embodiments of the disclosed methods, regimens, useskits, and pharmaceutical compositions, the patient is ACPA +. Select normal / abnormal and reference ranges for ACPA, ESR, RF and CRP may be found, e.g., in Fischbach and Dunning (2009) "A Manual of Laboratory and Diagnosite Tests"

(

8 th Edition) Wolters Kluwer/Lippincott Williams and Williams, which is incorporated by reference herein in its entirety. As used herein, the phrase "high risk RA patient" is used to define a patient that: a) is RF+, ACPA+ or both RF+ and ACPA+; and b) has a high level of CRP (or hsCRP), a high ESR, or both a high level of CRP and a high ESR. In some embodiments of the disclosed methods, regimens, uses, kits, and phamaceutical compositions, the patient is a high risk RA patient. In some embodiments, the patient presents with involvement of at least one, two, three four, five, six, seven, eight; nine or ten small joints. In some embodiments, thepatient presents with involvement of at least one, two, three four, five six, seven,"eight nine or ten largejoints. In some embodiments, the patient presents with involvement of greater than ten joints, with at least one of the joints being a small joint. In some embodiments, the patient has duration of symptoms of at least six weeks. "Joint involvement" refers to any swollen or tender joint on examination, which may be confirmed by imaging evidence of synovitis. Categories of joint distribution are classified according to the location and number of involved joints, with placement into the highest category possible based on the pattern ofjoint involvement, "Large joints" refers to shoulders, elbows, hips, knees, and ankles. "Small joints" refers to the metacarpophalangeal joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints, thumb interphalangeal joints, and wrists. In some embodiments of the disclosed methods, regimens, uses, kits and compositions, a patient has 2 6 out of 28 tender joints and 6 out of 28 swollen joints and hsCRP > 10 mg/L -28- WO 2012/059598 PCT/EP2011/069476 54388 FF "Duration of symptoms" refers to patient self-report of the duration of signs or symptoms of synovitis (e.g., pain, swelling, tenderness) ofjoints that are clinically involved at the time of assessment, regardless of treatment status. As used herein, "selecting a high risk RA patient for treatment" and "selecting a patient for treatment on the basis of the patient being a high risk RA patient" and "selected for treatment" is used to mean that a particular RA patient is chosen from a larger group or RA patients based on that particular patient fulfilling the high risk RA criteria (i.e., the patient is RF+, ACPA+, or both RF+ and ACPA+; and the patient has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR). As used herein, the phrase."has been previously treated for RA" is used to mean a patient that has previously undergone RA treatmettusing an antirheuratic agent, e.g,, the patient is a failure, an inadequate responder, or intolerant to a previots:RA therapy, antdrheumatic agent or treatment regimen. Such patients include hosepreviously-treated with MTX, DMARD&, and/or biologics, such as TNF alpha antagonists, etc. In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has been previously treated for RA. As used herein, the phrase "has not been previously treated for RA" is used to mean a patient that has not previously undergone RA treatment using an anti-rheumatic agen, i.e., the patient is "nafve". In some embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient has not been previously treated for RA. As used herein, a "failure" to a previous RA therapy refers to: (1) a patient who has no meaningful clinical benefit (primary lack of efficacy); (2) a patient who has a measurable and meaningful response, but for whom response could be better, e.g., low RA disease activity or RA remission was not achieved (also termed "inadequate response"); (3) a patient who, after an initial good response, worsens (secondary loss of efficacy); and (4) a patient who has a good response but discontinues because of a side effect (also termed "intolerance"). Patients who show TNF inadequate response (TNF-IR) or intolerance to TNF would be considered TNF failures. Patients who show methotrexate inadequate response (MTX4R) or intolerance to MTX would be considered MTX failures. Patients who show DMARD inadequate response (DMARD-IR) or intolerance to DMARDs would be considered DMARD failures. In some - 29 - WO 2012/059598 PCTIEP2011/069476 54388 FF embodiments of the disclosed methods, regimens, uses, kits, and pharmaceutical compositions, the patient is a TNF failure, a MTX failure, or a DMARD failure. By "therapeutic regimen" is meant the pattern of treatment of an illness, e.g., the pattern of dosing used during the treatment of RA. A therapeutic regimen may include an induction regimen and a maintenance regimen. Examples of therapeutic regirmens for treatment of RA are given in Table 2, none of which provide for treatment of i high risk RA patient. Standard Route Induction Regimen Maintenane.Regimen ADALIMUMAB s.c. NA 40 mg every other week. Some Humira@ patients with RA not-receiving methotrexate may benefit from increasing the frequency to 40 mg every week. ETANERCEPT s.c. NA 50 mg once weekly with or without Enbrel@ methotrexate (MTX). 1NFLIXIMAB iv. 3 mg/kg at 0; 2, and 6 3 mig/kg every 8 weeks thereafter. For Remicade@ weeks patients who have an incomplete response, consideration may be given to adjusting the dose up to 10.mg/kg or treating as often as every 4 weeks, CERTOLIZUMAB PEGOL s.C. 400 mg (given as two sc. 200 mg every other week; for Cimzia@ doses of'200 mg) initially maintenance dosing, 400 mg every 4 and at weeks 2 and 4. weeks can be considered. GOLIMUMAB Simponi@ s.C. NA 50 mg administered once a month, ANAKINRA Kineret @ s.c. NA 1.00 mg/day administered daily. RITUXIMAB i'.v. two. 1000 mg IV infusions Subsequent courses should be Rituxan@ separatedby 2 weeks (one . administered every 24 weeks or based course). on clinical evaluation, but not sooner than every 16 weeks, .ABATACEPT Orencia@ i.v, <61%g = 500 mg; Every 4 weeks thereafter. 60to 100 kg:= 750 mg; >00kg 1000tng initially, then 2 and 4 weeks after initial infusion TOCILIZUMAB Actemra® iv. NA 4 mg/kg once every 4 weeks followed by an increase to 8 mg/kg based on clinical response, Table 2: Examples of therapeutic regimens for biological treatment of rheumatoid arthritis (RA) The phrase "induction regimen" or "induction period" refers to a treatment regimen (or the portion of a treatment regimen) that is used for the initial treatment of a disease. In some embodiments, the disclosed methods, uses, kits, processes and regimens (e.g., methods of treating an inflammatory arthridities, e.g., RA, such as a high risk RA patient) employ an induction regimen. The general goal of an induction regimen is to provide a high level of drug to - 30 - WO 2012/059598 PCT/EP2011/069476 54388 FF a patient during the initial period of a treatmentregimen. An. induction regimen may employ (in part or in whole) administration of a greater dose of the drug than a physician would employ during a maintenance regimen, administering a drug more frequently than a physician would administer the drug during a maintenance regimen, or both. In some embodiments of the disclosed methods, uses, kits, processes and regimens the induction dose may be delivered druing an induction regimen as a single high dose infusion (e.g., about 30 mg/kg). Alternatively, an induction dose may be delivered as several (e.g., two or three) infusions (e.g., about 10 mg/kg). Alternatively, an induction dose may be delivered as several. (e.g., 1,2, 3, 4, 5 6 or more) subcutaneous injections (e.g., about 75-300 mg). Delivery of drug during an induction regimen may be via a subcutaneous (s.c.) route, e.g., delivery of dosages of about 75 mg - about 300 mg s.c. (e.g., about 75 mg s.c., about 150 mg s.c., about 300 mg s.c,), or via an intravenous (i.v.) route, e.g., delivery of dosages of about 1 mg/kg - about 30 mg/kg i.v. (e.g., about I mg/kg, about 3 mg/kg, about 10 mg/kg, about 30 mg/kg) or any other route of administration (e.g, intramuscular, im.). In some embodiements of the disclosed methods, compositions, kits, uses and regimens the IL-i 7 antagonist (e.g. secukinumab) is delivered by Lv. administration during at least a portion of the induction regimen. In some embodiments, the induction regimen comprises administering a dose of about I mg/kg - about 30 mg/kg, about I mg/kg - about 10 mg/kg, preferably about 10 mg/kg of the IL-17 antagonist (e.g., secukinumab). In further embodiments, the induction doses are delivered weekly, bi-weekly, every other week, or monthly, preferably every other week. In further embodiments, the induction regimen employs I - 10 doses of the IL-17 antagonist (e.g., secukinumab), preferably three doses of the IL-17 antagonist (e.g., secukitiumab). An induction regimen for delivery of an IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an IL- 7 receptor binding molecule (e.g. an IL- 17 receptor antibody) may also be designed using PK information (see Table 10), rather than specific dosages. For the disclosed uses, regimens and methods (e.g., methods of treating an inflammatory arthridities, e.g., RA, such as a high risk RA patient), an artisan may deliver an IL 17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-1 7 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody) during an induction regimen to provide an average Cms of about 360 pg/mL - about 401 pg/mL; Altematively, an artisan may deliver an IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an 11-17 antibody, - 31 - WO 2012/059598 PCT/EP2011/069476 54388 FF such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody) during an induction regimen to provide an average Cm of about 401 pg/mL, with up to about a 30%-40% [+ or -] inter-patient variation for an average 90 kg human. Alternatively, an artisan may deliver an IL-17 antagonist, e.g., an JL-17 binding molecule (eg., an IL-17 antibody, such as secukinumab) or an L-17 receptorbinding molecule (e.g., an IL-1 7 receptor antibody) during an induction regimen to provide an average Cmu of about 360 pg/mL for an average 75 kg human. Alternatively, an artisan may deliver an IL-17 antagonist, e.g., an IL- 17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL- 17 receptor antibody) during an induction regimen to provide trough levels over 80 jg/mL over a 10 week period for an average 75.kg human In some embodiments, the IL-I7 antagonist is delivered week 0, 2 and 4 iv. during an induction regimen to provide an average average C,, of about 401 pg/nL, with up to about a 30%-40% [+ or -i inter-patient variation for an average 90 kg human. In some embodiments, the IL-i7 antagonist is delivered week 0,.2 and 4 i.v. during an induction regimen to provide an average average C, of about 360 pglmL for an average 75 kg human. In other embodiments, the IL-17 antagonist is delivered week 0, 2 and 4 i.v. during an induction regimen to provide trough levels over 80 g/LrnL over a 10 week period for an average 75 kg human. The phrase "maintenance regimen" or "maintenance period" refers to a treatment regimen (or the portion of a treatment regimen) that is used for the maintenance of a patient during treatment of an illness, e.g., to keep the patient in remission for long periods of time.(months or years). In some embodiments the disclosed methods, uses and regimens (e.g., methods of treating an inflammatory arthridities, e.g., RA, such as a high risk RA patient) employ a maintenance regimen. A maintenance regimen may employ continuous therapy (e.g, administering a drug at a regular intervals, e.g., weekly, monthly, yearly, etc.) or intermittent therapy (e.g., interrupted treatment, intermittent treatment, treatment at relapse, or treatment upon achievement-of a particular predetermined criteria [e.g., pain, disease manifestation, etc.]). Delivery of an IL-17 antagonist, e.g., IL-l binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) during a maintenance regimen may be via a subcutaneous route, e.g., delivery of dosages of about 75 mg - about 300 mg s.c. (e.g., about 75 mg s.c., about 150 mg s.c., about 300 mg s.c.), or via an intravenous route, e.g., delivery of - 32 - WO 2012/059598 PCT/EP2011/069476 54388 FF dosages of about about 1 mg/kg - about 30 mg/kg. Lv. (e.g., about I mg/kg, about 3 mg/kg, about 10 mg/kg, about 30 mg/kg), or any other route of administration (e.g, intramuscular, im.). In some embodiments of the disclosed methods, uses and regimens, the IL- 17 antagonist (e.g., secukinumab) is delivered by s.c. administration during the maintenance regimen. In some embodiments, the maintenance regimen comprises-administering a dose ofabout 75 mg - about 300 mg, about 75 mg - about 150 mgpreferably about 75 mg or about 150 mg of the IL-17 antagonist (e.g., secukinumab). In some embodiments, the maintenance regimen comprises administering a dose of the IL-i7 antagonist (e.g,, secukinumab) on a monthly basis. A maintenance regimen for delivery of an L-I 7 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an tL-17 receptor binding molecule (e.g., an IL- 17 receptor antibody) may also be designed using PK information (see Table 9), rather than specific dosages. For the disclosed uses, regimens and methods (e.g., methods of treating an inflammatory arthridities, e.g., RA, such as a high risk RA patient), an artisan may deliver an IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-I7 antibody,. such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody) during a maintenance regimen to provide an average steady-state trough level of about 9.4 pg/mL - about 31 1 .g/mL (e.g., about 9.4 pg/mL, about 17.3 Rg/mL, about 31 pg/mL), with up to about a 30% [+ or -] inter-patient variation for an average 75 kg (e.g., 71-79 kg) human. Alternatively, an artisan may deliver an IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g, an IL- 17 receptor antibody) during a maintenance regimen to provide an average steady-state trough level of about 8.0 pg/mL - about 30.0 gg/mL (e.g.,about 8.0 pg/mL,,about 17 pg/mt, about 30 pg/mL) for an average 75 kg human. In some embodiments, the IL-I? antagonist is delivered monthly during a maintenance regimen to provide an average steady-state trough level of about 9.4 pg/mL - about 31 pg/mL (e.g., about 9.4 pg/mL, about 17.3 pg/mL, about 31 pg/mL), with up to about a 30% [+ or -] inter-patient variation for an average 70 kg human. In other embodiments, the IL-17 antagonist is delivered monthly during a maintenance regimen to provide an average steady-state trough level of about 8.0 pg/mL - about 30.0 pg/mL (e.g., about 8.0 pg/mL, about 17 pg/mL, about 30 pg/mL) for an average 75 kg human. Alternatively, an artisan may deliver an IL-17 antagonist, e.g., an IL- 17 binding molecule (eig., an IL- 17 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody) during a maintenance - 33 - WO 2012/059598 PCT/EP2011/069476 54388 FF regimen to provide a mean AUC tau at steady state of about 314 ng*day/L - about 1323 ng*day/L (e.g., about 314 mg*day/L to about 1-256 mg*day/L, e g., about 31 mg*day/L to about 1323 mg*day/L). The timing of dosing is generally measured from the day ofthe first dose of secukinumab (which is also known as "baseline"). However, different health care providers use different naming conventions, as shown in Table 3, below. Week 10/1 11/2 2/5 3/4 1 4/ 15/6 6/7 1 VS 18/9 19/10 10/1.1etc I" day 0/1 718 14/15 12 8/M 9 35/36 42/43 49/50 1 5/57 63/64 70/71 etc. Table 3 - Common naming conventions for dosing regimens. Bolded items refer to the naming convention used herein, Notably, week zero may be referred to as week one in some naming conventions, while day zero may be referred to as day one in some naming conventions, Thus, it is possible that different physicians will designate, e.g,, a dose as being given during week 3 / on day 21, during week 3 / on day 22, during week 4 / on day 21, during week 4 / on day 22, while referring to the same dosing schedule. For consistency, as used herein, the first week of dosing will be referred to as week zero, while the first day of dosing will be referred to as day 1. Thus, as an example, four induction doses of seoukinumab administered weeklyduing an induction regimeh would be provided during week 0 (e.g., on about day I), during week I (e.g., on about day 8), during week 2 (e.g., on about day 15), and during week 3 (e.g., on about day 22). Induction doses may be administered every two weeks (i.e., every other week), e~g., during week 0, during week 2, during week 4, etc. Induction doses may be administered every three weeks, e.g., during week 0, during week 3, during week 6, etc. Induction doses may be administered daily for one week, e.g., on day I - 7. It must be noted, however, that this naming convention is only used for clarity, and should not be construed as limiting. As used herein, the phrase "means for administering" is used to indicate any available implement for systemically administering a biologic, including, but not limited to, a pre-filled syringe, a vial and syringe, an injection pen, an autoinjector, an iv. drip and bag, a pump, etc. With such items, a patient may self-administer the drug (i.e., administer the drug on their own behalf) or a physician may administer the drug. - 34,- WO 2012/059598 PCT/EP2011/069476 54388 FF Various aspects of the disclosure are described in further detail in the flowing subsections. All patents, patent applications, references and other publications are incorporated by reference herein in their entirety. IL-17 Antagonists The various disclosed pharmaceutical compositions, regimens, processes, uses, methods and kits utilize an IL-17 antagonist, e.g,, IL-17 binding molecule (e.g., [L-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (eig., IL-17 antibody or antigen binding fragment thereof), In one embodiment, the IL-17 antagonist, e'g.. FL-17 biding moletde (e.gjIL-17 antibody or antigen binding fragment thereof; eg., secukinumab), comprises at least one immunoglobulin heavy chain variable domain (V14) comprising-in sequence hypervariable regions CDRI, CDR2 and CDR3, said CDRl having the amino acid sequence SEQ ID NO:1 (N Y-W-M-N), said CDR2 having the anino acid sequence SEQ ID NO:2 (A-I-N-Q-D-G-S-E-K-Y Y-V-G-S-V-K-G), and said CDR3 having the amino acid sequence SEQ ID NO:3 (D-Y-Y-D-1 L-T-D-Y-Y-I-H-Y-W-Y-F-D-L), In one embodiment, the IL-17 antagonist, e.g.,IL- 17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises at least one immunoglobulin light chain variable domain (VL) comprising in sequence hypervariable regions CDRl', CDR2' and CDR3', said CDR ' having the amino acid sequence SEQ ID NO:4 (R-A-S Q-S-V-S-S-S-Y-L-A), said CDR2' having the amino acid sequence SEQ ID NO:5 (G-A-S-S-R A-T) and said CDR3' having the amino acid sequence SEQ ID NO:6 (Q-Q-Y-G-S-S-P-C-T). In one embodiment, the IL- 17 antagonist, e.g., IL-17 binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises at least one immunoglobulin heavy chain variable domain (VM) comprising in sequence hypervariable regions CDRI-x, CDR2-x and CDR3-x, said CDR1-x having the amino acid sequence SEQ ID NO: I (G-F-T-F-S-N-Y-W-M-N) said CDR2-x having the amino acid sequence SEQ ID NO.12 (A-I-N-Q-D-G-S-E-K-Y-Y), and said CDR3-x having the anino acid sequence SEQ ID-NO:13 (C-V-R-D-Y-Y-D-l-L-T-D-Y-Y--H-Y-W-Y-F-D-L-W-G). In one embodiment, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., iL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises at least one - 35 - WO 2012/059598 PCT/EP2011/069476 54388 FF immunoglobulin V 8 domain and at least one immunoglobulin 1 L domain, wherein: a) the immunoglobulin VH domain comprises: i) hypervariable regions CDRI, CDR2 and CDR3, said CDR1 having the amino acid sequence SEQ ID NO: 1, said CDR2 having the amino acid sequence SEQ ID NO:2, and said CDR3 having the amino acid sequence SEQ ID NO:3; or ii)hypervariable regions CDRI -x, CDR2-x and CDR3-x, said:CDRi-x having the amino acid sequence SEQ ID NO: 11, said CDR2-x having the.amino acid sequenceSEQ 1D NO12, and said CDR3-x having the amino acid sequence SEQ ID NO:13; adb) the immunoglobulin VL domain comprises hypervariable regions CDR I, CDR2' and CDR3', said CDR P having the amino acid sequence SEQ ID NO:4 said CDR2' having the amino acid sequence SEQ ID NO:5, and said CDR3' having the amino acid sequence SEQ ID NO:6 or. In one embodiment, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises at least one immunoglobulin VH domain and at least one immunoglobulin VL domain, wherein: a) the at least one immunoglobulin V4 domain comprises in sequence hypervariable regions CDRI, CDR27and CDR3, said CDRI having the amino acid sequence SEQ. ID NO: 1, said CDR2 having the amino acid sequence SEQ ID NO:2, and said CDR3 having the amino acid sequence SEQ ID NO:3; and b) the at least one immunoglobulin VL domain comprises in sequence hypervariable regions CDR I', CDR2' and CDR3', said CDR ' having the amino acid sequence SEQ ID NO:4, said CDR2' having the amino acid sequence SEQ ID NO:5, and said CDR3' having the amino acid sequence SEQ ID NO:6, in one embodiment, tthe IL- 17antagonist, e.g., IL-17 binding molecule (e.g, IL-17 antibody or antigen binding fragment thereof, e.g.,secukinumab), comprises:at least-one immunoglobulin VH domain and at least one immunoglobulin t domain, wherein: a) the at least one immunoglobulin VH domain comprises in sequence hypervariable regions CDRI -x, CDR2-x and CDR3-x, said CDR I-x having the amino acid sequence SEQ ID NO:] 1, said CDR2-x having the amino acid sequence SEQ ID NO:12, and said CDR3-x having the amino acid sequence SEQ ID NO:13; and b) the at least one immunoglobulin VL domain comprises in sequence hypervariable regions CDR ', CDR2' and CDR3', said CDR P having the amino acid sequence SEQ ID NO:4, said CDR2' having the amino acid sequence SEQ ID NO:5, and said CDR3' having the amino acid sequence SEQ ID NO:6. - 36 - WO 2012/059598 PCT/EP2011/069476 54388 FF In one embodiment, the IL-17 antagonist, eg-, IL-17 binding molecule (eig., 117-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises: a) an immunoglobulin heavy chain variable domain (VH) comprising the amino acid sequence set forth as SEQ ID NO:8; b) an immunoglobulin light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO:0; c) an immunoglobulin VH domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth as SEQ ID NO:10; d) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID ND:1, SEQ ID NO:2, and SEQ ID NO:3 e) an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; f) an iminunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO:12 and SEQ ID NO:13; g) an immunoglobulin Vq domain comprising the hypervariable regions set forth as SEQ ID NO: I, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth :as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or h) an immunoglobulin Vi 1 domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:3.and an Imnunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 ad SEQ ID NO:6. For ease of reference the amino acid sequences of the hypervariable regions of the secukinumab monoclonal antibodies, based on the Kabat definition and as determined by the X ray analysis andusing the approach of Chothia and coworkers, is provided in Table 4, below, Light-chain CDRI' Kabat R-A-S-Q-S-V-S-S-S-Y-L-A (SEQ ID NO:4) Chothia/X-ray R-A-S-Q-S-V-S-S-Y-LA (SEQ ID NO:4) CDR2' Kabat G-A-S-S4R-A-T (SEQ ID:NO:5) Chothia/ X-ray G-A-S-S-R-A-T (SEQ ID NO:5) CDR3' Kabat Q-Q-Y-G-S-S-P-C-T (SEQ ID NO:6) Chothia/ X-ray Q-Q-Y-G-S-S-P-C-T (SEQ ID NO:6) Heavy-chain CDRI Kabat N-Y-W-M-N (SEQ ID NO:]) -37- WO 2012/059598 PCT/EP2011/069476 54388 FF CDR I -x Chothia/ X-ray G-F-T-F-S-N-Y-W-M-N (SEQ ID NO:l 1) CDR2 Kabat A-l-N-Q-D-G-S-E-K-Y-Y-V-G-S-V-K.G (SEQ ID NO:2) CDR2-x Chothia/ X-ray A-I-N-Q-D-G-S-E-K-Y-Y (SEQ ID NO: 12) CDR3 Kabat D-Y-Y-D-IL-T-D-Y-Y-I-H-Y-WY-F-D-L (SEQ ID NO;3) CDR3-x Chothia/ X-ray C-V-R-D-Y-Y-D-1-L-T-D-Y-Y4-i-Y-W-Y-F-D-L-W-G (SEQ ID NO:13) Table 4: Amino acid sequences of the hypervariable regions of the secukinumab monoclonal antibodies. Amino acid highlighted in bold are part of the CDR loops, while those shown in plain style are part of the antibody framework. In preferred emboditfents, the viable domains of both heavy and light chains are of human origin, for instance those of the secukinumab antibody which are shown in SEQ ID NO:10 (= variable domain of light chain, i.e., amino acid I to 109 of SEQ ID NO:10) and SEQ ID NO:8 (= variable domain of heavy chain, i.e., amino acid I to 127 of SEQ ID NO:8). The constant region domains preferably also comprise suitable human constant region domains, for instance as described in "Sequences of Proteins of Immunological Interest", Kabat E.A. et al, US Department of Health and Human Services, Public Health Service, National Institute of Health. In some embodiments, the IL-i 7 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the variable light domain of SEQ ID NO:10. In other embodiments, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the variable heavy domain of SEQ ID NO:8. In other embodiments, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the variable light domain of SEQ ID NO:10 and the variable heavy domain of SEQ ID NO:8. In some embodiments, the IL-17 antagonist, e.g., IL 17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, egg., secukinumab), comprises the three CDRs of SEQ ID NO: 10. In other embodiments, the IL47 antagonist, e.g., IL- 17 binding molecule (e.g., 1L1-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the three CDRs of SEQ ID NO:8, In other embodiments, an the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the three CDRs of SEQ ID NO:10 and the three -38- WO 2012/059598 PCT/EP2011/069476 54388 FF CDRs of SEQ ID NO:8. CDRs of SEQ ID NO:8 and SEQ ID NO:10, according to both the Chothia and Kabat definition, may be found in Table 4. In some embodiments, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g;, IL- 17 antibody or antigen binding fragment thereof, eg., secukinumab), comprises the light domain of SEQ ID NO:15. In other embodiments, the IL47 antagonist, egg.,.IL-17 binding molecule (e.g., IL- 17 antibody-or antigen binding fragment thereof, eig.,secukinumab), comprises the heavy domain of SEQ ID NO:T1. In otler emnboinmets; ie L-P7 antagonist e g,,IL-7 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g' secukinuiah), comprises the light domain of SEQ ID NO:I5 and the heavy domain of SEQ ID NO:17. In some embodiments, the IL-17 antagonist, e.g.,.IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment themof, e.g., secukinumab), comprises the three CDRs of SEQ ID NO: 15. In other embodiments, the IL-17 antagonist, e.g., IL-I7 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the three CDRs of SEQ ID NO:17. In other embodiments, the IL-1l antagonist, e.g. IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), comprises the three CDRs of SEQ ID NO: 15 and the three CDRs of SEQ ID NO: 17. CDRs of SEQ ID NO:15 and SEQ ID NO: 17, according to both the Chothia and Kabat definition, may be found in Table 4. Hypervariable regions may be associated with any kind of framework regions, though preferably are of human origin. Suitable framework regions are described in Kabat E.A. et al, ibid. The preferred heavy chain framework is a human heavy chain framework, fbr instance that of the secukinunab antibody. It consists in sequence, e.g,, of FRI (amino acid1 to 30 of SEQ ID NO:8), FR2 (amino acid 36 to 49 of SEQ ID NO:R), FR3 (amino acid 67 to 98 of SEQ ID NO:8) and FR4 (amino acid 117 to 127 of SEQ ID NO:8) regions. Taking into consideration the determined hypervariable regions of secukinumab by X-ray analysis, another preferred heavy chain framework consists in sequence of FRI -x (amino acid I to 25 of SEQ ID NO:8), FR2-x (amino acid 36 to 49 of SEQ ID NO:8), FR3-x (amino acid 61 to 95 of SEQ ID NO:8) and FR4 (amino acid 119 to 127 of SEQ ID NO:8) regions. In a similar manner, the light chain framework consists, insequence, of FR ' (amino acid I to 23 of SEQ ID NO:l0), FR2' (amino acid 36 to 50 of SEQ ID NO: 10), FR3' (amino acid 58 to 89 of SEQ ID NO: 10) and FR4' (amino acid 99 to 109 of SEQ ID NO: 10) regions. - 39 - WO 2012/059598 PCTIEP2011/069476 54388 FF In one embodiment, the IL-4 7 antagonist, eg,.IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof e.g., secukinumab) is selected from a human anti IL- 17 antibody, which comprises at least: a) an immunoglobulin heavy chain or fragment thereof which comprises a variable domain comprising in sequence the hypervariable regions CDR 1, CDR2 and CDR3 and the constant part or fragment thereof of a human heavy chain; said CDR l having the amino acid sequence SEQ ID NO: 1, said CDR2 having the amino acid sequence SEQ ID NO:2, and said CDR3 having the amino acid sequence SEQ ID NO:3; and b) an immunoglobulin light chain or fragment thereof, which comprises a variable domain comprising in sequence the hypervariable regions CDR 1', CDR2', and CDR3' and the constant part or fragment thereof of a human light chain, said CDRl' having the amino acid sequence SEQ ID NO: 4, said CDR2' having the amino acid sequence SEQ ID NO:5, and said CDR3 having the amino acid sequence SEQ ID NO:6. In one embodiment, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g,, IL-17 antibody or antigen binding fragment thereof eig., secukinumab) is selected from a single chain binding molecule, whidh corprisesarn antigen binding site comprising: a) a fifst domain comprising in sequence the hypervariable regions CDRi, CDR2 and CDR3, said CDR I having the amino acid sequence SEQ ID NO:1, said CDR2 havingthe amino acid sequence SEQ ID NO:2, and said CDR3 having the amino acid sequence SEQ ID NO:3; and b) a second domain comprising the hypervariable regions CDR ', CDR2' and CDR3', said CDRP having the amino acid sequence SEQ ID NO:4, said CDR2' having the amino acid sequence SEQ ID NO:5, and said CDR3' having the amino acid sequence SEQ [D NO:6; and c) a peptide linker which is bound either to the N-terminal extremity of the first domain and to the C-terminal extremity of the second domain or to the C-terminal extremity of the first domain and to the N-terminal extremity of the second domain. Alternatively, the IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) may comprise at least one antigen binding site comprising at least one immunoglobulin heavy chain variable domain (VH) which comprises in sequence: a) hypervariable regions CDR1 (SEQ ID NO:1), CDR2 (SEQ ID NO:2) and CDR3 (SEQ ID NO:3); or b) hypervariable regions CDR li, CDR2i, CDR3i, said hypervariable region CDR1L differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDRI as shown in SEQ ID NO:1,.said hypervariable region CDR2 1 differs by 3, preferably 2, - 40 - WO 2012/059598 PCT/EP2011/069476 54388 FF more preferably I amino acid(s) from the hypervariable region of CDR2 as shown in SEQ ID NO:2; and said hypervariable region CDR3 1 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR3 as shown in SEQ ID NO:3; and said binding IL 17 molecule is capable of inhibiting the activity of about I nM (= 30ng/ml) human IL-17 at a concentration of about 50 nM or less, about 20 rnM or less, about 10 nM or less, about 5 nM or less, about 2 nM or less, or more preferably of about I nMor less of said molecule by 50%, said inhibitory activity being measured on IL-6 production induced by bu-IL-17 in human dermal fibroblasts. Similarly, the IL-1 antagoiist, eig., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, eg., secukinumnab) may comprise at least one antigen binding site comprising at least one immunoglobulin heavy chain variable domain (Va) which comprises in sequence: a) hypervariable regions CDRI-x (SEQ D NO:l 1), CDR2-X (SEQ ID NO:12) and CDR3-x (SEQ ID NO:13); or b) hypervariable regions CDR i-x, CDR2-x, CDR3 1 -x, said hypervariable region CDRl j-x differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR I -x as shown in SEQ ID NO: 11, said hypervariable region CDR2-x differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR2-x as shown in SEQ ID NO: 12; and said hypervariable region CDR3j-x differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR3-x as shown in SEQ ID NO: 13: and said binding IL-17 molecule is capable of inhibiting the activity of I nM (= 30ng/ml) human IL-17 at a concentration of about 50 nM or less,.about 20 nM or less, about 10 nM or less, about 5 nM or less, about 2 nM or less, or more preferably of about I nM or less of said molecule by 50%, said inhibitory activity being measured on IL-6 production induced by hu-IL-17 in human dermal fibroblasts. Similarly, the IL-17 antagonist, e.g., IL-i 7 binding molecule (e.g., IL-I7 antibody or antigen binding fragment thereof, esg., secukinumab) may comprise at least one antigen binding site comprising at least one immunoglobulin light chain variable domain (V 1 ) which comprises in sequence: a) hypervariable regions CDRl (SEQ ID NO:4), CDR'2 (SEQ ID NO:5). and CDR'3 (SEQ ID NO:6); or b) hypervariable regions CDR1 L( CDR2, CDR3, said hypervariable region CDR' Ii differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR'[ as shown in SEQ ID NO:4, said hypervariable region CDR'2i differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of - 41 - WO 2012/059598 PCT/EP2011/069476 54388 FF CDR'2 as shown in SEQ ID NO:5; and said hypervariable region CDR'3 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR'3.as shown in SEQ ID NO:6; and said binding IL-1 7 molecule is capable of inhibiting the activity of I nM (= 30rig/mi) human IL- 17 at.a concentration of-about 50 nM or less, about 20 nM or less, about 10 rIM or less, about 5 ntM or less aboutn2 aM or less, or morepreferably of about 1 nM or less of said molecule by 50%, said inhibitory activity being.measured on IL-6 production induced by iu-IL 17 in human dermal fibroblasts. Alternatively, the I

L

-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) may comprise both heavy (VH) and light chain (VL) variable domains and said IL-17 binding molecule having at least one antigen binding site comprising: a) an immunoglobulin heavy chain variable domain (V) which comprises in sequence hypervariable regions CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO:2) and CDR3 (SEQ ID NO: ); and an immunoglobutin light chain variable domain (V.) which comprises in sequence hypervariable regions CDRI' (SEQ ID NO:4), CDR2 (SEQ ID NO:5) and CDR3 (SEQ ID NO:6); or b) an immunoglobulin heavy chain variable domain (Vfj) which comprises in sequence hypervariable regions CDRli, CDR2, and CDR3i, said hypervariable region CDRI i differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR1 as shown in SEQ ID NO: 1, said hypervariable region CDR2 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervarlable region of CDR2 as shown in SEQ ID NO:2; and said.hypervariable region CDR3 1 differs by 3-, preferably 2, more preferably I amino acid(s) from the hypervariable region -of CDR3 as shown in SEQ ID NO:3; and an immunoglobulin light chain variable domain (VL) whichcomprises in:sequence hypervariable regions CDRI ', CDR2's CDR3', said hypervariable region CDR' l differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR'l as shown in SEQ ID NO:4, said hypervariable region CDR'2 1 differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR'2 as shown in SEQ ID NO:5; and said hypervariable region CDR'3 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR'3 as shown in SEQ ID NO:6; and said binding IL-17 molecule is capable of inhibiting the activity of 1 nM (= 30ng/ml) human IL-17 at a concentration of about 50 nM or less, about 20 nM or less, about 10 nM or less, about 5 nM or less, about 2 nM or less, - 42 - WO 2012/059598 PCTEP2011/069476 54388 FP or more preferably of about I nM or less of said molecult by 50%, said inhibitory activity beidg Measured on IL-6 production:induted by huIL-17 in human derrnal fibroblasts. Alternatively, the IL-17 antagonist, e.g., IL-17 binding molecule (eg., IL-17-antibody or antigen binding fragment thereof, e.g., secukinumab) may comprise both heavy (V.) and light chain (VL) variable domains and said IL-17 binding molecule comprises at least one antigen binding site comprising: a) an immunoglobulin heavy chain variable domain (V4) which comprises in sequence hypervariable regions CDRI-x (SEQ ID NO:l 1), CDR2-x (SEQ ID NO:12) and CDR3-x (SEQ ID NO:13); and an immunoglobulin light chain variable domain (VL) which comprises in sequence hypervariable regions CDR 1' (SEQ ID NO:4t .CDR2' (SEQ ID NO: 5) and CDR3' (SEQ ID NO:6); or b) an immunoglobulin heavy chain variable domain (VH) which comprises in sequence hypervariable regions CDRI 1 -x, CDk2-x, and CDR3r-x, said hypervariable region hypervari able regions CDR I l-x, CDR2-x, CDR3i-x, said hypervariable region CDRi-x differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR l-x as shown in SEQ ID NO: i1, said hypervariable region CDR2 x differs by 3, preferably .2, more preferably I amino acid(s) from the hypervariable region of CDR2-x as shown in SEQ ID NO: 12; and said hypervariable region CDR3j-x differs by 3, preferably 2, more preferably 1 amino acid(s) fror the hypervariabit region of CDR3-x as shown in SEQ ID NO: 13; and an immunoglobulin light chain variable domain (VL) which comprises in sequence hypervariable regions CDR l'i, CDR2' 1 , CDR3'i, said hypervariable region CDR' 1 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR'1 as shown in SEQ ID NO: 4, said hypervariable region CDR'2 1 differs by 3, preferably 2, more preferably I amino acid(s) from the hypervariable region of CDR'2 as shown in SEQ ID NO:5; and said hypervariable region CDR'3 1 differs by 3, preferably 2, more preferably 1 amino acid(s) from the hypervariable region of CDR'3 as shown in SEQ ID NO:6; and said binding IL-17 molecule is capable of inhibiting the activity of ] nM (= 30 ng/ml) human IL-17 at a concentration of about 50 nM or less, about 20 nM or less, about 10 nM or less; about 5 nM or less, about 2 nM.or less, or more preferably of about I nM or less of said molecule by 50%, said inhibitory activity being measured on IL-6 production induced by hu-IL-17 in human dermal fibroblasts. A human IL-17 antibody disclosed herein may comprise a heavy chain that is substantially identical to that set forth as SEQ ID NO: 17 and a light chain that is substantially identical to that -43- WO 2012/059598 PCT/EP2011/069476 54388 FF set forth as SEQ ID NO: 15. A human IL-1 7 antibody disclosed herein may comprise a heavy chain that comprises SEQ ID NO: 17 and a light chain that comprises SEQ ID NO: 15. A human ILA7 antibody disclosed herein may comprise: a) one heavy chain which comprises a variable domain having an amino acid sequence substantially identica[to that shown in SEQ ID NO:8 and the constant part of a human -heavy.:chain; and b) one light chain which comprises a variable domain having an amino acid sequence substantially identical to that shown in SEQ ID NO: 10 and the constant part of a human light chain. The inhibition of the binding of IL-I 7 to its receptor may be conveniently tested in various assays including such assays as. described in WO 2006/013107. By the term "to the same extent" is meant that the reference and the derivative molecules exhibit, on a statistical basis, essentially identical IL-I7 inhibitory activity in one of the assays referred to herein (see Example ! of WO2006/013107). For exaniple, the IL-1 7 ending molecules disclosed herein typically havelCsos for the inhibition of humanIL-17:on.bL6 production induced bylunian IL 17 in human dermal fibroblasts which are below about 10 nM, more preferably about 9, 8, 7, 6, 5, 4, 3, 2, or about I nM of that of, preferably substantially the same as, the FC 50 of the corresponding reference molecule when assayed as described in Example 1 of WO 2006/013107. Alternatively, the assay used may be an assay of competitive inhibition of binding of IL-17 by soluble IL-17 receptors (eg. the human IL-17 R/Fc constructs of Example I of WO 2006/013107) and the IL-17 binding molecules of the disclosure. The disclosure also includes [L-17 antagonists, e.g., IL-1 7 binding molecules (e.g., IL-1 7 antibody or antigen binding fragment thereof, e.g., secukinumab) in which one or more of the amino acid residues of CDR1, CDR2, CDR3, CDR I-x, CDR2-x, CDR3-x, CDRI', CDR2' or CDR3' or the frameworks, typically only a few (e.g., 1-4), are changed; for instance by mutation, e.g., site directed mutagenesis of the corresponding DNA sequences, The disclosure includes the DNA sequences coding for such changed IL-17 binding molecules. In particular the disclosure includes IL-17 binding molecules in which one or more residues of CDR 'or CDR2' have been changed from the residues shown in SEQ ID NO:4 (for CDRF) and SEQ ID NO:5 (for CDR2'). The diselosure also includes IL-7antangoists, eg, tL- 7 binding molecules.(e g,1L-17 antibody or antigen binding fragment thereof, e.g., secukinumab) that have binding specificity for human IL-17, in particular IL-17 antibodies capable of inhibitingthe binding of IL-17 to its receptor and IL- 17 antibodies capable of inhibiting the activity of I riM (= 30 ng/ml) human IL - 44 - WO 2012/059598 PCTIEP2011/069476 54388 FF 17 at a concentration of about 50 nM or less, about 20 nM or less, about 10 nM or less, about 5 nM or less, about 2 nM or less, or more preferably of about I nM or less of said molecule by 50% (said inhibitory activity being measured on IL-6 production induced by hu-ILL17 in human dermal fibroblasts). The disclosure provides methods for treating RA, comprising administering a therapeutically effective amount of an IL-17 antagonist, qg., IL-17 binding molecule (e.g, IL-17 antibody or antigen binding fragment thereof; e.g, secukiniumab)to a subject sufferingfrom RA, e.g., a high risk RA patient, In some embodiments-, the IL-17 antibody, e.g., secukinumab, binds to an epitope of mature human IL-17 comprising Leu74, Tyr85, His86, Met87, Asn88, Vail 24, Thr125, Prol26, Ile127, Val128, HisI29. In some embodiments, the IL-17 antibody, e.g., secukinumab, binds to an epitope of mature human IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp8O. In some embodiments, the IL-17 antibody, e.g., secukinumab, binds-to an epitope of an IL-17 hornodimer having two mature human IL-17 chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val24, Thrl25, Prol-26, Ile127, Vall28 Hisl29 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain. The residue numbering scheme used to define these epitopes is based on residue one being the first amino acid of the mature protein (le., JL-J 7A lacking the 23 amino acid N-terminal signal peptide and beginning with Glycine). The sequence for immature IL-17A is set forth in the Swiss-Prot entry Q16552. In some embodiments, the IL-17 antibody has a KD of about 100-200 pM. In some embodiments, the ILA7 antibody has an ICsa of about (.4nM for in vitro neutralization of the biological activity ofaboutA067 aM humanrIL-17A. In some embodiments the absolute bioavailability of subcutaneousy (sg.c.) administered IL-i7 antibody has a range of about 60 about g0%, e.g., about 76%. In some embodiments, the IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL- 17 antibody, such as secukinumab) or an IL-l 7 receptor binding molecule (e.g., an IL-1 7 receptor antibody) has an elimination half-life of about 4 weeks (e.g., about 23 to about 30 days, e.g., about 30 days). In some embodiments, the IL-17 antagonist, e.g., an IL-17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL-17 receptor antibody) has a Tm. of about 7-8 days. In some embodiments of the disclosed methods, uses, pharmaceutical compositions, kits, assays, and treatment regimens, the IL-17 antagonist is selected from the group consisting of: a) an IL-17 binding molecule or an IL-17 receptor binding molecule; b)secukinumab; c) an IL-17 - 45 - WO 2012/059598 PCT/EP2011/069476 54388 FF antibody that binds to an epitopeof1L-17 Tomprising Leu74 TyrS5, HisS Met87, Asn88, Val124, Thr]25, Pro126, lle127, ValI28, FHisI29; d) an TL-17 anybody that binds to an epitope of IL-17 comprising Tyr43, Tyr44, Arg46, Ala79, Asp80; e) an IL.17 antibody that binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, MetB7, Asn88, Val124, Thrl25, Pro126, Ile127, Val28, HIs129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Aspg0 on the other chain; f an IL-7 antibody that binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, MetS7, Asn8, VaI124, ThrI25, Prol26, Ile127, Vall28, His 129 on one chain and Tyr43, Tyr44, Arg46, A1a79, Asp80 on the other chain, wherein the IL 17 binding molecule has a K of about 100-200 pM, and wherein the IL-17 binding molecule has an in vivo half-life of about 4 weeks; and g) an IL-i7 antibody that comprises an antibody selected from the group consisting of: i) an immunoglobulin heavy chain variable domain (VU) comprising the amino acid sequence set forth as SEQ ID NO:8; ii) an immunoglobulin light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO: 10; iii) an. immunoglobulin V domain comipriaingthe amino acid sequence set forth as SEQ ID NOr8 and an immunoglobulin V1, domain comprising the amino acid sequence set forth as SEQ ID NO: 10; iv) an immunoglobulin VH domain comprising the hypervariable regions set.forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3; v) an immunoglobulin V domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; vi) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13; vii) an immunoglobulin VF domain comprising the hypervariable regions set forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and viii) an immunoglobulin V, domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO:13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. Particularly preferred IL-17 antagonists, e.g., IL-17 binding molecules (e.g., IL- 7 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e.g., IL-17.antibody or antigen binding fragment thereof) for use in the disclosed methods, uses, kits, etc. are human antibodies, especially secukinumab as described in Examples -46 - WO 2012/059598 PCT/EP2011/069476 54388 FF I and 2 of WO 2006/013107. Secukinumab (AIN457) is a recombinant high-affinity, fully human monoclonal anti-human interleukin-17A (IL-17A, IL-17) antibody of the IgGl/kappa isotype. Secukinumab (see, e.g., W02006)011107 and W02007/l17749) has a very high affinity for IL-I 7, i.e., a K 0 of about 100-200 pM and an IC 50 for in vitro neutralization of the biological activity of about 0.67 nM human IL-17A of about 0.4nM. Thus, secukinumab inhibits antigen at a molar ratio of about 1:1. This high binding affinity makes the secukinumab antibody particularly suitable for therapeutic applications. Furthermore, it has been determined that secukinumab has a very long half life, i.e., about 4 weeks, which allows for prolonged periods: between administration, an exceptional property when treating chronic life-long disorders, such as rheumafiod arthritis (RA). Treatment Regimens, Methods of Treatment, Pharmaeutical Compositions and Uses The disclosed IL-17 antagonists, e.g., [L-17 binding molecules (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL- 17 receptor binding molecules (e.g., IL-i 7 antibody or antigen binding fragment thereof) are useful for the treatment, prevention, or amelioration of inflammatory arthritis (e.g., rheumatoid arthritis (RA), spondyloarthropathy, ankylosing spondylitis, and psoriatic arthritis). Thus, such molecules are useful in inducing changes in the signs and symptoms of arthritis & structural changes, preventing further joint erosion, improving joint structrue, etc. In some embodiments, the patient having inflammatory arthritis is an RA patient, e.g., a high risk RA patient. The IL-17 antagonists, e.g., IL-17 binding molecules (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e.g., IL-17 antibody or antigen binding fragment thereof) may be used in vitro, ex vivo, or incorporated into pharmaceutical compositions and administered to individuals (e.g., human subjects) in vivo to treat, ameliorate, or prevent RA, e g., in high risk RA patients. A pharmaceutical composition will be formulated to be compatible with its intended route of administration (eig., oral compositions generally include an inert diluent or an edible carier). Other nonlimitingexamples of routes of administration include parenteral (e.g., intravenous), intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. The pharmaceutical compositions compatible with each intended route are well known in the art. - 47 - WO 20121059598 PCT/EP20 11069476 54388 Pp The IL-17 antagonists, e.g., IL-17 binding molecules (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecules (e.g., IL-1 7 antibody or antigen binding fragment thereof) may be used as a pharmaceutical composition when combined with a pharmaceutically acceptable carrier. Such a composition may contain, in addition to an ILI 7 antagonist. (e.g. ,secukinumab) carriers, various diluents, fillers, salts, buffers, stabilizers, sotubilizers,:and other materials well known ihe art. The characteristics of the carrier will Idepend on ihe route of administration. The pharmaceuticalcompositions for-use in the disclosed methods may also contain additional therapeutic agents for treatment of the particular targeted disorder. For example, a pharmaceutical composition may also include anti-inflammatory agents. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with the IL-I 7 antagonist (e.g., secukinumab), or to minimize side effects caused by the IL- 17 binding molecules. The pharmaceutical composition of the disclosure may be in the form of a liposome in which the IL-17 antagonist, e.g., IL-1.7 binding molecule (e.g;, IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids that exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithin, phospholipids, saponin, bile acids; etc, In. practicing the methodsof treatment, regiinena, uses, etc. of the present disclosure, a therapeutically effective amount of an IL-I7 antagorfist, e.g., IL-47 binding molecule (e.g., IL-l7 antibody or antigen binding fragment thereof, e.g., secukinumab) or iL-17 receptor binding molecule (e.g., IL-I 7 antibody or antigen binding fragment thereof) is administered to a subject, e.g., a mammal (e.g., a human). An IL-17 antagonist (e.g., secukinumab) may be administered in accordance with the method of the disclosure either alone or in combination with other therapies, such as, e.g., in combination with additional therapies for inflammation. When coadministered with one or more agents, an IL-17 antagonist (e.g., seoukinumab) may be administered either simultaneously with the other agent, or sequentially. If administered - 48 - WO 2012/059598 PCT/EP2011/069476 54388 FF sequentially, the attending physician will decide on the appropriate sequence of administering the IL- 17 antagonist (e.g., secukinumab) in combination with other agents. When a therapeutically effective amount of an TIL-47 antagonist, e.g., IL-17ibindihg molecule (e.g., IL-17 antibody or antigen binding fragment thereof,:e.g, secuknumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment: thereof) is administered orally, the binding agent will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical Composition of the disclosure may additionally contain a solid carrier such as a gelatin or an adjuvant. When administered in liquid form, a. liquid, carrier such as water, petroleum, oils of animal or plant origin such as peanut oil (exercising caution in relation to peanut allergies), mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form of the pharmaceutical composition may further contain components such as physiological saline. solution, dextrose or other saceharide solution, or glycols such as ethylene glycol, propylene glycol, or polyethylene glycol, When a therapeutically effective amount of an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g, secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) is administered by intravenous, cutaneous or subcutaneous injection, the IL 17 binding molecule will be in the:form of a pyrogen-free, parenterally acceptable solution. A pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection may contain, in addition to the IL-I 7 antagonist (e.g., secukinumab), an isotonic vehicle such as sodium chloride, Ringefs, dextrose, dextrose and sodium chloride, lactated Ringers, or other vehicle as known in the art. Pharmaceutical compositions for use in the disclosed methods may be manufactured in conventional manner. In one embodiment, the pharmaceutical composition is preferably provided in lyophilized form. For immediate administration it is dissolved in a suitable aqueous carrier, for example sterile water for injection or sterile buffered physiological saline. If it is considered desirable to make up a solution of larger volume for administration by infusion rather than a bolus injection, may be advantageous to incorporate human semm albumin or the patient's own heparinised blood into the saline at the time of formulation. The presence of an excess of such physiologically inert protein prevents loss of antibody by adsorption onto the walls of the container and tubing used with the infusion solution. If albumin is used, a suitable concentration - 49 - WO 2012/059598 PCT/EP2011/069476 54388 FF is from 0.5 to 4.5% by weight of the saline solution. Other formulations comprise liquid or lyophilized formulation, The appropriate dosage will, of course, vary depending upon, for example, the particular IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptorbinding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) to be employed, the host the mode of administration and the nature and severity of the condition being treated, and on the nature of prior treatments that the patient has undergone. Ultimately, the attending health care providerwill decide the amount of the IL 17 antagonist %eg, secukinumab) with whichto treat each individual subject. In some embodiments; the attending healthcare provider may administer low doses-of the:IL-17 binding molecule and observe the subject's response, In other embodiments, the initial dose(s) of IL-I7 antagonist (e.g., secukinumab) administered to a subject are highand then are itrated downward until signs of relapse occur, Larger doses of the IL-17 antagonist (e.g., secukinumab-)may be administered until the optimal therapeutic effect is obtained for the subject, and at that point the dosage is not generally increased further, An IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) is conveniently administered parenterally, intravenously, e.g. into the antecubital or other peripheral vein, intramuscularly, or subcutaneously, The duration of intravenous (i.v.) therapy using a pharmaceutical composition of the present disclosure will vary, depending on the severity of the disease being treated and.the condition and personal response of each individual patient. Also contemplated is subcutaneous (s.c.) therapy using a pharmaceutical composition of the present disclosure. The health care provider will decide on the appropriate duration of Ev. or s.c. therapy and the tiring of administration of the therapy, using the pharmaceutical composition of the present disclosure. Satisfactory results (treatment, prophylaxisi delay of onset of symptoms) are generally indicated to be obtained at dosages from about 0.05 mg to about 30 mg per kilogram body weight, more usually from about 0.1 mg to about 20 mg per kilogram body weight. The frequency of dosing may be in the range from about once per day up to about once every three months, e.g., in the range from about once every 2 weeks up to about once every 12 weeks, e.g., - 50 - WO 2012/059598 PCT/EP2011/069476 54388 FF once every four to eight weeks. The dosing frequency will depend on, inter alia, the phase of the treatment regimen. The use of antibodies as the active ingredient of pharmaceuticals is now widespread, including the products HERCEPTINTM (trastuzumab), RITUXANTM (rituximab), SYNAGSTM (palivizumab), etc. Techniques for pudicatida of antibodies toaglharmaceutical grade are Well known in the art.Antibodiese.g., antibodies to I , aretpicallylbrmulated either in aqueous form ready for parenteral administration oras lyophilisates forreconstitution with a suitable diluent prior to administration. In some embodiments of the disclosed methods and uses, the.IL 17 antagonist, e.g., IL-17 antibody, e.g,, secukinumab, is formulated as a lyophilisate. Suitable lyophilisate formulations can be reconstituted in a small liquid volume (e.g, 2ml or less) to allow. subcutaneous administration and can provide solutions with low levels of antibody aggregation. The composition will usually be sterile, at least at the time of its formation. The composition will usually be non pyrogenic e;g. containing <I EU (endotoxin unit, a standard measure) per dose, and preferably <0.] EU per dose. The coniposition is preferably gluten free. Within formulations disclosed herein, antibodies preferably makes up at least 80% by weight (e.g. at least 90%, 95%, 97%, 98%, 99% or more) of the total protein in the formulation. The antibody is thus in purified form. Lyophilisates Techniques for lyophilisation of antibodies are well known in the art, e.g., see Rey & May (2004) Freeze-Drying/Lyophilization Of Pharmaceutical & Biological Products ISBN .0824748689, WO92/1.5331, US pateif applications 2008/0286280, WO03/04l 637, W02008/116103, W02008/029908, W02007/074880,W003/009817, and WO98/022136. For example, antibody products SYNAGISTM, REMICADETM, RAPTIVATM, SIMULECTTM, XOLAIRTM and HERCEPTNTM are supplied as lyophilisates. These antibodies are reconstituted to various final concentrations, e.g. SIMULECTTM, is reconstituted to a concentration of 4 mg/ml antibody, REMICADETM is reconstituted to a concentration of 10 mg/mI, HERCEPTINTM to 21 mg/ml, SYNAGISTM and RAPTIVATM to 100 mg/ml, and XOLAIRTh to 125 mg/ml. Lyophilisates of the disclosure can be reconstituted to give aqueous compositions with an anti-IL-1 7 antibody concentration of at least about 15 mg/ml. The antibody concentration can be much higher than about 15 mg/ml, e.g., > about 15 mg/ml,> about 20 mg/ml, > about 25 mg/ml, - 51 - WO 2012/059598 PCT/EP2011/069476 54388 FF > about 50 nmg/mi, > about 75 mg/mI, >about:100 mg/ml,>about 125 mg/mil, > about 150 mg/ml, > about 300 mg/ml or higher. The lyophilisate may include, in addition to the anti-IL-17antibody, further components such as one or more of the following: (i) a sugar; (ii) a buffering agent; (iii) a surfactant; and (iv) a stabilizing agent. Inclusion of each of such additional components (i), (ii) and (iii) is typical, and can give compositions with low aggregation of the anti-IL-U7 antibody. Inclusion of component (iv) is advantageous because it has been shown to further reduce aggregation after storage. When present, components (I) to (iv) will be at a pre-lyophilisation concentration sufficient to maintain the anti-IL-17 antibody in a form which is active-and soluble after storage (under normal conditions) and reconstitution. The components will also be present after reconstitution. Suitable sugars for use with the invention include, but are not limited to, monosaccharides, disaccharides and trisaccharides. For example, the sugar may be sucrose, trehalose, raffinose, maltose, sorbitol or mannitol. The sugar may be a sugar alcohol or an amino sugar. Sucrose and trehalose (eg, at a concentration of about 175 mM to about 300 rnM e.g., about 175 mM, about 180 mM, about 185 mM, about 190 MM, about 195 mM, about 200 mM, about 225 mM, about 250 mM, about 275 mM, about 300 mM) are particularly useful. Suitable buffering agents for use with the invention include, but are not limited to, a histidine buffer, a citrate buffer, a phosphate buffer, a succinate buffer, an acetate buffer, or a Tris buffer. A histidine buffer (e.g., at a concentration of about 5 mM to about 50 mM, e.g., about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, about 50 mM) is particularly useful, Suitable surfactants for use with the invention include, but ate not limited to, non ionic surfactants, ionic surfactants and zwitterionic surfactants. Typical surfactants for use with the invention include, but are not limited to, sorbitan fatty acid esters (e.g., sorbitan monocaprylate, sorbitan monolaurate, sorbitan monopalmitate), sorbitan trioleate, glycerine fatty acid esters (e.g., glycerine monocaprylate, glycerine monomyristate, glycerine monostearate), polyglycerine fatty acid esters (e.g., decaglyceryl monostearate, decaglyceryl distearate, decaglyceryl monolinoleate), polyoxyethylene. sorbitan fatty acid esters (e.g., polyoxyethylene sorbitan monolaurate, polyoxyethylene sorbitan monooleate, .polyoxyethylene sorbitan monostearate, -52- WO 2012/059598 PCT/EP2011/069476 34388 FF polyoxyethylene sorbitan monopalmitate, polyoxyethylene sorbitan trioleate, polyoxyethylene sorbitan tristearate), polyoxyethylene sorbitol fatty acid esters (e.g., polyoxyethyldne sorbitof tetrastearate, polyoxyethylene sorbitol tetraoleate), polyoxyethylene glycerine fatty acid esters (e.g., polyoxyethylene glyceryl monostearate), polyethylene glycol fatty acid esters (e.g., polyethylene glycol distearate), polyoxyethylene alkyl ethers (eng., polyoxyethylene lauryl ether), polyoxyethylene polyoxypropylene alkyl ethers (e.g., polyoxyethylene polyoxypropylene glycol, polyoxyethylene polyoxypropylene propyl ether, polyoxyethylene polyoxypropylene cetyl ether), polyoxyethylene alkylphenyl ethers (e.g., polyoxyethylene nonylphenyl ether), polyoxyethylene hydrogenated castor oils (e.g. polyoxyethylene castor oil polyoxyethylene hydrogenated castor oil), polyoxyethylene beeswax derivatives (eg., polyoxyethylene sorbitol beeswax), polyoxyethylene lanolin derivatives (e.g., polyoxyethylooe lanolin),atid polyoxyethylene fatty acid amides (e.g., polyoxyethylene stearic acid amide);:C1O-ClS alkyl sulfates (e.g., sodium cetyl sulfate, sodium lauryl sulfate, sodium oleyl sulfate), polyoxyethylene C10-Cl ealkyl ether sulfate with an average of 2 to 4 moles of ethylene oxide units added (e.g., sodium polyoxyethylene lauryl sulfate), and CI-CI8 alkyl sulfosuccinate ester salts (e.g., sodium lauryl sulfosuccinate ester); and natural surfactants such as lecithin, glycerophospholipid, sphingophospholipids (e.g., sphingomyelin), and sucrose esters of C12-C18 fatty acids. A composition may include one or more of these surfactants. Preferred surfactants are polyoxyethylene sorbitan fatty acid esters e.g. polysorbate 20, 40, 60 or 80. Polysorbate 80 (Tween 80) (e.g., at a concentration of about 0.01% - about 0.1%, e.g., about 0.02%, about 0.04%, about 0.06%, about 0.08%, about 0.1%) is particularly useful, A lyophilisate may include active ingredients in addition to the antibody. For instance, further pharmacological agents may be included, such as chemotherapeutic compounds. For instance, methotrexate may be included, and it is known to include methotrexate sodium in lyophilisates. The pH of an aqueous antibodyformulation prior to lyophilisation may be in the range 4.0-8.0, which a pH in the range about.5.5- about 7.4 being typical, e.g., about 5,5, about 5.6, about 53, about 5;8, about 5.9, about 6, about 6.2, about 6:4, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4. Disclosed are antibody lyophilisates comprising about 25 mg, 50 mg, 75 mg, 150 mg, or 300 mg of an anti-IL-17 antibody - preferably 75mg - 150 mg (e.g., 75 mg or 150 mg) of an - 53 - WO 2012/059598 PCT/EP2011/069476 54388 Ip anti-IL-17 antibody. Disclosed are also lyophilisates comprising: an IL-17 antibody, e.g., secukinumab; a sugar; a buffering agent; and a surfactant. The composition may also include a stabilizing agent. Disclosed are also processes for preparing a lyophilisate, comprising steps of: (i) preparing An aqueous solution comprising an IL- 17 antibody, e g, secukinumabt, a sugar, a buffering agent, a surfactant, and optionally a stabilizing agent.and (ii) lyophilising the aqueous solution. Reconstituates Before a lyophilisate can be administered to a patient it should be reconstituted with a liquid reconstituent (e.g., an aqueous liquid) to provide a liquid composition (hereinafter a "reconstituate"). Lyophilisates may be reconstituted with various volumes (e.g., 0.25 ml, 0.5 ml, 1.0 ml, 1.5 nl, etc,) of a reconstituent (eig., an aqueous reconstituent, e.g., water).. This step permits antibody and other components in the lyophilisate to re-dissolve to give a solution which is suitable fbr injection to a patient. The volume of aqueous material used for reconstitution dictates the concentration of antibody in a resulting pharmaceutical composition, and may also determine the route of administration. Reconstitution with a smaller volume of reconstituent than the pre-lyophilisation volume provides a composition which is more concentrated than before lyophilisation. As mentioned above, lyophilisates of the invention can be reconstituted to give aqueous compositions with an anti-IL-17 antibody concentration of at least about 75 mg/mi (or higher), and the volume of reconstituent will be selected accordingly. Disclosed herein are reconstituates comprising an anti-lL47 antibody, wherein the reconstituate has an antibody concentration of at leastabout 25 mg/ml, 50 mg/ml, 75 mg/mi, 150 mg/ml, or 300 mg/mI - preferably 75 mg/ml - 150 mg/mI (e.g., 75 mg/nil or 150 mg/nl); Ideally the volume of the reconstituate is small, e.g., 0.25-2.0 ml, in order to facilitate subcutaneous administration of the IL-17 antagonist. Typical reconstituents for lyophilised antibodies include sterile water or buffer, optionally containing a preservative. If the lyophilisate includes a buffering agent, then the reconstituent may include further buffering agent (which may be the same as or different from the lyophilisate's buffering agent) or it may instead include no buffering agent (e.g. WFI, - 54 - WO 2012/059598 PCT/EP2011/069476 54388 FF physiological saline). A reconstituate may include pharmacological agents, sudh as chemotherapeutic compounds, facilitating codelivery together with the antibody. When present, components (i) to (iv) mentioned above will be at a concentration sufficient to maintain the anti-IL-17 antibody in active soluble form, after reconstitution, under normal storage conditions while retaining pharmaceutical acceptability at the point of use. In addition to antibody and water, reconstituates may include further components, derived from the lyophilisate and/or the reconstituent. Such components include, but are not limited to, buffers, salts, stabilizing agents, glycerol, alcohols, preservatives, surfactants, etc. A thorough discussion of such pharmaceutical ingredients is available in Gennaro (2000) Remington: The Science and Practice of Pharmacy. 20th edition, ISBN: 0683306472. Disclosed are reconstituate pharmaceutical compositions comprising: an IL-17 antibody, e.g., secukinumab; a sugar; a buffering agent; and a surfactant, The composition may also include a stabilizing agent. Disclosed are also processes for preparing a reconstituate, comprising mixing a lyophilisate with an aqueous reconstituent, wherein the lyophilisate comprises an IL-17 antibody, e.g, seoukinumab, a sugar, a buffering agent, a surfactant, and optionally astabilizing agent. Disclosed herein are methods oftreating rheumatoid arthritis (RA), comprising administering a therapeutically effective amount ofan IL-17 antagonist to a high risk RA patient. Disclosed herein are also methods of treating rheumatoid arthritis (RA), comprising: a) selecting a patient for treatment on the basis of the patient being a high risk RA patient; and b) administering a therapeutically effective amount of an 1L-17 antagonist to the patient. Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising: a) assaying a sample from a patient for: i. rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and ii. C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR; and b) thereafter, administering the patient an IL-17 antagonist to the patient if the patient is RF+, ACPA +, or RF+ and ACPA + and the patient has a high level of CRP, a high ESR, or a high level of CRP and a high ESR. Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising administering a therapeutically effective amount of an IL-17 antagonist to a patient,. provided that the patient is selected for treatment on the basis oft a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESRi or both a high level of CRP and a high - 55 - WO 2012/059598 PCT/EP2011/069476 54388 FF ESR. In some embodiments, the step of administering comprises: a) administering the IL-17 antagonist to the patient during an induction regimen; and b) thereafter administering the IL-17 antagonist to the patient during a maintenance regimen. Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising: a) administering a high risk RA patient three doses of about t O mg/kg of an IL- 17 antagonist each of the three doses being delivered every other week; and b) thereafter administering about 75 mg - about 150 mg of the IL-17 antagonist to the patient every month, beginning one month from delivery of the third intravenous dose. Disclosed herein are therapeutic regimens for treating rheumatoid arthritis (RA), comprising: a) selecting a patient having RA based on the fotidwing criteria; i. the patient is RF+, ACPA+, or both RF+ and ACPA+;:and ii the patient has a.high level of-CRP, a high ESR, or both a high level of CRP and a high ESt; andb) administering the patient three doses Qf about 10 mg/kg of an IL-] 7 antagonist, the first dose being delivered during week zero, the second dose being delivered during week two, and the third dose being delivered during week four; and c) thereafter administering the patient about 75 mg - about 150 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight. Disclosed herein are IL-I 7 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL-17 antagonist is to be administered to a high risk RA patient. Disclosed herein are IL-17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL-1 7 antagonist is to be administered to a patient selected for treatment on the basis of the patient being a high risk RA patient. Disclosed herein are IL- 17 antagonists for use in treating a high risk RA patient. In some embodiments, the high risk RA patient: a) is seropositive for rheumatoid factor (RF+), anti citrullinated protein antibody (ACPA+), or both RF+ and ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a high level of CRP and a high ESR. In some embodiments, a high level of CRP is > 10 mg/L, as measured by hsCRP. In some embodiments, a high ESR is >28 mm/h. Disclosed herein are IL-17 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL- 17 antagonist is to be administered to a patient, provided that the patient is selected for treatment on the basis of: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. - 56 - WO 2012/059598 PCT/EP2011/069476 54388 FF Disclosed herein are IL-1 7 antagonists for use in treating rheumatoid arthritis (RA), characterized in that the IL-17 antagonist is to be: a) administered to a high risk RA patient as three doses of about 10 mg/kg, each of the three doses being delivered every other week; and b) thereafter administered to the patient. as a dose of about 75 mg - about 150 Mg every month, beginning one month f6r delivery of ththid intravenous dose Disclosed herein are IL-I 7 antagonists-for use in treating rheumatoid arthritis (RA-), characterized in that: a) a sample from patient is assayed for: i, rheumatoid factor iRE), anti citrullinated protein antibody (ACPA), or RF and ACPA; and ii.C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR),-or both CRP and an ESR; and b) the IL-17 antagonist is administered to the patient if the patient is RF+, ACPA +, or RF+ and ACPA + and the patient has a high level of CRP, a high ESR, or a high level of CRP and a high ESR. Disclosed herein are uses of an IL-17 antagonist for the manufacture of a medicament for treating RA, characterized in that the IL-I antagonist is to be-administered to high risk RA patient. Disclosed herein are uses of an IL-17 antagonist for the manufacture of a medicament for treating RA, characterized in that the IL-17 antagonist is to be administered to high risk RA patient during an induction regimen followed by a maintenance regimen. Disclosed herein are pharmaceutical composition for treating RA, comprising as an active ingredient an IL-17 antagonist, wherein the Mw 17 antagonist is to be administered to a high risk RA patient. Disclosed herein are pharmaceutical composition for treating RA, comprising as an active ingredient an IL- 17 antagonist, wherein the IL-I7 antagonist is to be Administered to a high risk RA patient during an induction regimen followed by a maintenance regimen. Disclosed herein are therapeutic regimens for treating RA, comprising: a) selecting a high risk RA patient; b) administering about 10 mg/kg of an IL- 7 antagonist to the patient during weeks 0, 2 and 4; and c) thereafter administering about 75 mg - about 150 mg of the IL-17 antagonist to the patient monthly, beginning week 8. Disclosed herein are methods of treating a RA patient or a high risk RA patient, comprising: a) administering an IL-I7 binding molecule to a patient in need thereof during an induction regimen that provides a mean maximum plasma concentration (C,,) of the IL-17 binding molecule of about 360 pg/ml; and b) thereafter administering the IL-17 binding -57- WO 2012/059598 PCT/EP2011/069476 54388 FF molecule to the patient during a maintenance regimen tharprovides: i) an average steady-state trough level of theJIL-17 binding-mlecule- between about 8 jig/mI -about 30 jg/ml; and/or fi) a mean AUC tau at steady state ofabout'33! mg*day/L - about 1323 mg*day/L. Disclosed herein are IL-17 binding molecules for use in treating a RA patient or a high risk RA patient, characterized in that the IL-17 binding molecule: a) is tobe administered to the patient during an induction regimen that provides a mean maximum plasma concentration (Cm) of the IL-17 binding molecule of about 360 pg/mi; and b) thereafter, is to be administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 binding molecule between about 8 pg/ml - about 30 pg/ml;and/or ii) a mean AUC tau, at steady state of about 331 mg*day/L - about 1323 mg*day/L. Disclosed herein are methods of treating a high risk RA patient, comprising: a). administering an IL-17 binding molecule to a patient in need thereof during -an induction regimen that provides a mean maximum plasma concentration (C") of the IL-17 binding molecule of about 401 pg/ml; and b) thereafter administering the IL-I7 binding molecule to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the IL- 17 binding molecule of about 9.4 ptg/nl about 31 pg/ml; and/or ii) a mean AUC tau at steady state of about 314 mg*day/L - about 1256 mg*day/L. Disclosed herein are 1. L- binding molecule for use in treating psoriasis, characterized in that the IL-17 binding molecule: a) is to be administered to the patient during an induction regimen that provides a mean maximum plasma concentration (Cm) of the IL-17 binding molecule of about 40] pg/ml; and b) thereafter, is to be administered to the patient during a maintenance regimen that provides: i) an average steady-state trough level of the Ll-17 binding molecule of about 9.4 pg/ml - about 31 pg/ml; and/or ii) a mean AUC tau at steady state of about 314 mg*day/L - about 1256 mg*day/L. In some embodiments, the maintenance regimen provides an average steady-state trough level of the IL- 17 binding molecule of about 9.4 pg/ml -about 17.3 Rg/ml. In some embodiments, the maintenance provides an average steady-state trough level of the IL- 17 binding molecule of about 9.4 pg/mI or about 17.3 pg/mI. In some embodiments, the induction regimen comprises intravenous administration of the IL-17 binding molecule every other week. In some embodiments, the maintenance regimen comprises monthly subcutaneous administration of the IL-17 binding molecule. -58 - WO 2012/059598 PCT/EP2011/069476 54388 FF Disclosed herein are IL-L 7 antagonists in preparation of a medicament for the treatment of RA, provided that the patient is selected for the treatment on the basis of: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. Disclosed herein are IL-7I antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated to comprise containers, each container having a sufficient amount of the IL-17 antagonist to allow delivery of at least about 75 mg- about 150 mg IL-17 antagonist per unit dose. Disclosed herein are IL-174ntagonists for the muanufacture of a medicament for the treatment of RA ina patient characterized as: a) being RF-; ACPA+, or both RF+ and ACPA +; and b) having ahigh level of CRPa high ESP, or both a high level of CRP and a high ESR, wherein the medicament is formulated to comprise:Containers, each container having a sufficient amount of the IL-17 antagonist to allow delivery of at least about 10mg/kg per unit dose, Disclosed herein are IL-17 antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated at a dosage to allow intravenous delivery of about 10 mg/kg per unit dose. Disclosed herein are IL- 17 antagonists for the manufacture of a medicament for the treatment of RA in a patient characterized as: a) being RF+, ACPA+, or both RF+ and ACPA +; and b) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR, wherein the medicament is formulated at a dosage to allow subcutaneous delivery of about 75 mg - about 150 mg IL-17 antagonist per unit dose. Disclosed herein are in vitro test methods for selecting a patient for treatment of RA, comprising determining. if i. the patient is RP+, ACPA+, or both RF+ and ACPA+; and ii. the patient has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. In some embodiments of the disclosed in vitro test methods, the. patient has an improved therapeutic response to the following regimen: a) administering the patient three doses of about 10 mg/kg of an IL-17 antagonist, the first dose being delivered during week zero, the second dose being - 59 - WO 2012/059598 PCT/EP2011/069476 54388 FF delivered during week two, and the third dose being delivered during week four; and a) thereafter administering the patient about 75 mg - about 150 mg of the IL- 17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight. In some embodiments of the disclosed-methodsg kits,.uses, pharmaceutical compositions, and regimenls' thehigh fisk RA patient: a) isseropositive for theutnatdid factor (RFe-), anti citrullinated protein antibody (ACPA+), or both Rf+ and.ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a highlevel of CRP and a high ESR, In some embodiments, the high level of CRP is > 10 mg/L, as measured by hsCRP. In some embodiments, the high ESR is >28 mm/h. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the step of administering comprises intravenously administering three doses of about 10 mg/kg of the IL-17 antagonist to said patient, each of said doses being administered every other week. In sone embodiments, the step of administering comprises subcutaneously administering doses of about 75 mg - about 150 mg of the TL-17 antagonist to said patient, each of said doses being administered monthly. In some embodiments, the step of administering comprises: a) administering the IL-17 antagonist to the high risk RA patient during an induction regimen; and b) thereafter administering the IL-1 7 antagonist to the patient during a maintenance regimen. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the induction regimen comprises administering the patient three doses of about 10 mg/kg of the IL-17 antagonist. in some embodinents,the first dose of about 10 mg/kg.Js delivered during week zero, the second dose of about 10 mg/kg is delivered during week two, and the third dose of about 10 mg/kg is delivered during week four. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the maintenance regimen comprises administering the patient about 75 mg - about 300 mg of the IL-17 antagonist. In some embodiments, the maintenance regimen comprises subcutaneously administering the patient about 75 mg - about 300 mg of the IL- 17 antagonist twice a month, monthly, every two months or every three months. In some embodiments, the maintenance regimen comprises subcutaneously administering-the patient about 75 mg - about 150 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight. In some embodiments, the maintenance regimen comprises - 60 - WO 2012/059598 PCT/EP2011/069476 54388 FF subcutaneously administering the patient -about 75 mg pr about 150ig of the IL-17 antagonist monthly, beginning during week eight. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, prior to administering the IL-17 antagonist the patient had a previous RA treatment comprising administering at least one anti-rheumatic agent selected from the group consisting of an immunosuppressive agent, a disease-modifying anti-rheumatic drug (DMARD), a pain-control drug, a steroid, a non-steroidal anti-inflammatory drug (NSAID), a cytokine antagonist, a bone anabolic, atbone anti-resorptive, and combinations thereof, in some embodiments, the prior to administering the IL-7 antagonist the patient had a1n inadequate response to, had failure to or was intolerant to treatment with a DMA RD, a TNF alpha antagonist, or methotrexate. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the patient is additionally administered a therapeutically effective amount of at least one anti-rheumatic agent selected from the group consisting of an immunosuppressive agent, a DMARD, a pain-control drug, a steroid, a NSAID, a cytokine-antagonist, a bone anabolic, a bone anti-resorptive, and combinations thereof. In some embodiments of the disclosed methods klts; uses, pharmaceutical compositions, and regimens, the TL-17 antagonist is administered as three doses of about 10 mg/kg, each of-said doses being administered every other week. In some embodiments, the IL-17 antagonist is administered as doses of about 75 mg - about 300 mg, each of said doses being administered monthly. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-1 7 antagonist is to be administered to the patient during an induction regimen and thereafter administered to the patient during a maintenance regimen. In some embodiments, the induction regimen comprises administering the patient three doses of about 10 mg/kg of the IL-17 antagonist, In some embodiments, the first dose of about 10 mg/kg is delivered during week zero, the second dose of about 10 mg/kg is delivered during week two, and the third dose of about 10 mg/kg is delivered during week four. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the maintenance regimen comprises administering the patient about 75 mg - about 300 mg of the IL-17 antagonist. In some embodiments, the maintenance regimen comprises - 61 - WO 2012/059598 PCT/EP2011/069476 54388 FF subcutaneously administering the patient about 75 mg - about 300 mg of the IL-1 7 antagonist twice a month, monthly, every two months or every three months. In some embodiments, the maintenance regimen comprises subcutaneously administering the patient about 75 mg -about 150 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months, beginning during week eight, In some embbodiments, the maintenance regimen comprises subcutaneously administering the patient about 75 mg or about 150 mg ofthe IL-I7 antagonist monthly, beginning during week eight. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the high risk RA patient: a)is seropositive for rheumatoid factor (RF+), anti citrublinated protein antibody (ACPA+), or both RF+ and ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a high level of CRP and a high ESR, In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the induction regimen maintains the trough level of the IL-17 binding molecule above 80 pg/mI for a 10 week period, In some embodiments, the maintenance regimen provides an average steady-state trough level of the IL-17 binding molecule of about 8 Rg/mi -about 17 pg/ml. In some embodiments, the maintenance provides an average steady-state trough level of the IL-I7 binding molecule of about 8 pg/ml or about 17 pg/ni. In some embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-17 antagonist is an IL-17 binding molecule or an IL- 17 receptor binding molecule. In some embodiments, the IL-17 binding molecule or an IL-17 receptor binding molecule is an IL-i7 binding molecule (e.g., IL-17 antibody) selected from the group consisting of: a) secukinumab; b) an IL- 17 antibody that binds to an epitope of IL-I7 comprising Leu74, Tyr85, His86, Met87, Asn88, Vall24, Thr1 25, Prol26, IeI27, Val128, Hisi29; c) an IL-17 antibody that binds to an epitope of IL-17 comprising Tyr43, Tyr44, Arg46 Ala79, Asp80; d) an IL-7 antibody that binds to an epitope of an IL- 17 homodimer having two mature IL47 protein chains, said epitope comprising Leu74, Tyr85, His86 Met87, Asn88, V4Il24, Thr125, Prol26, 11e127, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp8O on the other chain; e) an IL-17 antibody that binds to an epitope of an IL-17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val 124, Thrl25, Pro126, Ile127, Vall28, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, AspSO on the - 62 - WO 2012/059598 PCT/EP2011/069476 54388 FF other chain, wherein the IL-I7 binding Molecule has a KD of about 100-200 pM, and wherein the IL-17 binding molecule has an in vivo half-life of about 4 weeks; and f) an IL-17 antibody that comprises an antibody selected from the group consisting of: i) an immunoglobulin heavy chain variable domain (VH) comprising the amino acid sequence set forth as SEQ ID NO:8; ii) an immunoglobulin light chain variable domain (V. comprising the amino. acid sequence set forth as SEQ ID NO: 10; ii) an immunoglobulin V4 domain comprising the minor acid sequence set forth as SEQ ID NO;& and an imnunoglobulin V, domain comprising the amino acid sequence set forth as SEQ ID NO: 10; iv) an immunoglobulin Vj domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3; v) an immunoglobulin V, domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; vi) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:l l, SEQ ID NO: 12 and SEQ ID NO: 13; vii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin V domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and viii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6, In preferred embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the.IL-1 7 binding molecule is a human antibody. In even more preferred embodiments of the disclosed methods, kits, uses, pharmaceutical compositions, and regimens, the IL-17 binding molecule is secukinumab. As used herein, the phrase "container having a sufficient amount of the IL- 17 antagonist to allow delivery of [a designated dose]" is used to mean that a given container (e.g., vial, pen, syringe) has disposed therein a volume of an IL-1 7 antagonist (e.g., as part of a pharmaceutical composition) that can be used to provide a desired dose. As an example, if a desired dose is 75 mg, then a clinician may use 2 ml from a container that contains an IL-17 antibody formulation with a concentration of 37.5 mg/ml, I ml from a container that contains an IL-17 antibody formulation with a concentration of 75 mg/ml, 0.5 ml from a container contains an IL-17 antibody formulation with a concentration of 150 mg/ml, etc. In each such case, these containers have a sufficient amount of the IL-1 7 antagonist to allow delivery of the desired 75 mg dose. - 63 - WO 2012/059598 PCT/EP2011/069476 54388 FF As used herein, thephrase"fomulated ata dosage to allow [route of administration] delivery of [a designated dose)" is used to meanthat a givewpharnnaceutical conposition can be used to provide a desired dose of an IL-17 antagonist, e.g., an IL-I7 antibody, e.g.. secukinumab, via a designated route of administration (e g., s.c. or i.v.). As an example, if a desired subcutaneous dose is 75 mg, then a clinician may use 2 ml of an IL-17 antibody formulation having a concentration of 37.5 mg/mi, I ml of an IL-17 antibody formulation having a concentration of 75 mg/ml, 0.5 ml of an IL- 17 antibody formulation having a concentration of 150 mg/ml, etc. In each such case, these IL-i 7 antibody formulations are-at a concentration high enough to allow subcutaneous delivery of the IL- 17 antibody. Subcutaneous delivery typically requires delivery of volumes of less than about 2 ml, preferably a volume of about Imi or less. In some embodiments, the induction regimen comprises administration of 1, 2, 3, 4, 5, 6, or more i.v. doses of the IL-17 antagonist (e.g., secukinumab), e.g., secukinumab, preferably one, two or three (most preferably three) doses of secukinumnab delivered every week, every other week, every three weeks or every four weeks (monthly). In some embodiments, the induction regimen comprises administration of 10 mg/kg 1v. of the IL-17 antagonist (e.g., secukinumab), e.g., secukinumab. In some embodiments, induction doses of the IL-17 antagonist (e.g.,.secukinurnab) may be administered as three iv. infusions (e;g., 10 mg/kg) every other week, i.e., during week zero (eig., day 1), during week two (e.g., about day 15), and during week four (e.g., about day 29). In some embodiments, induction doses may be administered as three iv. infusions (e.g., 10 mg/kg) every three weeks, i.e., during week zero (e.g., about day 1), during week three (eg., about day 22), and during week six (e.g., about day 43). In some embodiments, induction doses may be administered as three i.v. infusions (e.g., 10 mg/kg) every four weeks (monthly), i.e. during week zero (e.g., about day 1), during week four (e.g., about day 29), and during week eight (e.g., about day 57). In some embodiments, induction doses of the IL-17 antagonist (e.g., secukinumab) may be administered as two i.v. infusions (e.g., 10 mg/kg) every other week, i.e., during week zero (about day 1), and during week two (e.g., about day 15). In some embodiments, induction doses may be administered as two iv. infusions (e.g., 10 mg/kg) every three weeks, i.e., during week zero (e.g., about day 1) and during weekthree (e.g., about day 22). In some embodiments, - 64 - WO 2012/059598 PCT/EP20/11069476 54388 FF induction doses may be administered as two i.v. infusions (e.g., 10 mg/kg) every four weeks (monthly), i.e., during week zero (e.g., about day I) and during week four (e.g., about day 29). In some embodiments, induction doses of the IL-I7 antagonist (e~g., secukinumab) may be administered as a single high dose infusion, e.g., 30 mg/kg. In further embodiments, the induction regimen comprises administration of 1, 2, 3, 4, 5, 6, or more daily or weekly s.c. doses of the IL-I 7 antagonist (e.g, secukinumab), preferably three to five (e.g., four) weekly doses of secukinumab. In some embodiments, the induction dosage that may be administered daily or weekly is about 75 mg - about 300 mg of the IL-I 7 antagonist (e.g., secukinumab) delivered s.c. (e..g,-about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg). In some embodiments, the induction regimen comprises administrationof daily sxc doses of the IL-17 antagonist(e.g., secukinumab), e.g., daily sg..doses of secukinumab (e.g., about 75 mg - about 300 mg, e.g. about 75 mg - about 150 mg, e.g., about 75 mg or about 150 ing), delivered on days 1-7. In some embodiments, the induction regimen comprises administration of weekly s.c. doses of the IL- 17 antagonist (eg., secukinumab), e.g., weekly s.c. doses of secukinumab, delivered during week zero, one, two, and three. In other embodiments, the dose(s) secukinumab administered to a subject may be higher and more frequent (i.e., weekly for the first month of treatment) during an induction regimen, and then the patient may be maintained at a lower dose. In some embodiments, the maintenance regimen comprises subcutaneously administering the patient about 75 mg or about 150 mg of the IL-i 7 binding molecule if the patient weighs less than 90 kg. In some embodiments, the maintenance regimen comprises subcutaneously administering the patient about 150 mg or about 300 mg of the IL-17 binding molecule if the patient weighs more than or equal to 90 kg. For a maintenance regimen, a dose of the IL-17 antagonist (e.g., secukinumab) may be provided twice a month (i.e., every two weeks, bimonthly or every other week, i.e., about every 14 days), every month (i.e., every 4 weeks, i.e., about every 28 days), every two months (i.e., every other month or every 8 weeks, i.e., about every 56 days), or every three months (i.e., every 12 weeks, i.e., about every 84 days). As used herein, the date of the first dose of a maintenance regimen will be measured from the final dose of the induction regimen. Thus, as an example, if the final dose of the induction regimen is provided during week four, then a first dose as part of a -65- WO 2012/059598 PCT/EP2011/069476 54388 FF bimonthly maintenance regimen may be delivered during week six (about day 43), a first dose as part of a monthly maintenance regimen may be delivered during week eight (about day 57), a first dose as part of an every two month maintenance regimen may be delivered during week. twelve (about 85 days), a first dose as part of an every three month maintenance regimen may be delivered during week sixteen (about 113 days), m In seine bmbodiments, the first dose of the maintenance regimen is delivered every month (monthly, bout every four weeks), beginning one month (ie., about four weeks) from delivery of a final induction (eig., s.C. or Lv. induction) dose. In some embodiments, the first dose of the maintenance regimen is delivered every month (monthly, about every four weeks), beginning: one month (i.e.,.about four weeks) from delivery of a third i.v. induction dose. In some embodiments, the maintenance regimen comprises administration of the IL- 17 antagonist (e.g., secukinumab), e.g., about 75 mg - about 300 mg (e.g, about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg) delivered bimonthly, monthly, every two months or every three months. In some embodiments, the IL-17 antagonist (e.g., secukinumab) is delivered s.o. during the maintenance regimen. In a preferred embodiment, a maintenance dose is delivered monthly. In some embodiments, a first maintenance dose is delivered during week six (e.g., about day 43), seven (e.g., about day 50), eight (e.g., about day 57), nine (e.g., about day 64), ten (e.g., about day 71), eleven (e.g., about day 78), twelve (e.g., about day 85), or thirteen (e.g., about day 92) of the treatment regimen, and -then monthly (e.g., about every 4 weeks or about every 28 days) thereafter. In some embodimentsthe maintenance regimen comprises subcutaneously administering the patient about 75 mg - about 300mg (eg, about 75 ng. -about 150 mg, e.g., about 75 mg or about 150 mg) ofthe IL-17 antagonist (e~g., secukinumab) twice a month, monthly, every two months or every three months, beginning during week four, five, six, seven, eight, nine, ten, eleven, or twelve, preferably during week eight. Preferred treatment regimens for treating RA patients (e.g., high risk RA patients) and patients having other inflammatory arthritis, e.g., spondytoarthropathy, ankylosing spondylitis (AS), and psoriatic arthritis (PsA), are provided in Table 5: i.v, induction regimen (3 ZJOXevery other week) maintenance.reaimen (I 50or 300 ma) e first dose = during week 0 = first monthly dose= during week * second dose = during week 2 * every month (about 4 weeks) thereafter. 0 third dose = during week 4 . induction. reimen 3 x J-0 eve- three66 - 66 - WO 2012/059598 PCT/EP2011/069476 54388 FF * first dose = duhring:week0 e firt-monthly dose= duringweek.10 * second dose- dbringveek 3 - every month about4 weeks)thereafter * third dose = during week 6 . i.v. induction regimen (3 x 10 every month) maintenance rgimen * first dose = during week 0 e first monthly dose = during week 12 * second dose during week 4 * every month (about 4 weeks) thereafter a third dose =during week 8 Lv. induction regimen (2 x. 10 every other week) maintenance regimen * first dose - during week 0 0 first monthly dose = during week 6 0 second dose = during week 2 * every month (about 4 weeks) thereafter i.v. induction regimen (2 x 1 every three week) maintenance-regimen * first dose - during week 0 e first monthly dose = during week 7 " second dose = during.week 3 * .vry.moth about 4weeksthereafter i.v induction regimen (2 x. 10 ever month) maintenance regimen * first dose = during week 0 * flst monthly dose = during week 8 * second dose= during week * every month (about 4 weeks) thereafter, S.C. induction regimen (150 or 300mg weekly for 4 maintenance regimen doses) * first monthly dose = during week 7 * first weekly dose = during week 0 e every month (about 4 weeks) thereafter * second weekly dose = during week I * third weekly dose = during week 2 fourth weekly dose = during week -3 S.C. induction regimen (150 or 300mg daily) maintenance regimen * dose 1-7 = day 17 first monthly dose = during week 4 or 5 * eveiymonth about4 weeks) thereafter S.C. induction regimen (150 or 300mg weekly for. 5 maintenance regimen doses) * firstmonibly-dose = during week 8 Sfiasi weekly dose = during week * every-month (about 4 weeks) thereafter * second weekly dose = during week I * third weekly dose =during week 2 * fourth weekly dose= during week 3 * fifth weekly dose = during week 4 Table S: Preferred dosing regimens for treating RA patients (e.g., high risk RA patients) and patients having other inflammatory arthritis, e.g., spondyloarthropathy, ankylosing spondylitis, and psoriatic arthritis. It will be understood that a dose need not be provided at an exact time point, e.g., a dose due on day 29 could be provided, e.g., on day 24 to day 34. In some embodiments, the dosage of the IL- 17 antagonist (e.g., secukinumab) used in the disclosed induction and/or maintenance regimens (as the case may be) is based on the patient's weight (e.g., whether a patient is under or over 75 kg, 80 kg, 85 kg, 90 kg, 95 kg, 100 kg, 105 kg, etc. can be used to define a dosage of the IL-17 antagonist, e.g., secukinumab, for delivery to the patient). In one embodiment, the patient is administered about 75 mg or about 150 mg (e.g., delivered s.c.). if the patient weighs less than or equal to about 80.kg. In one embodiment, the patient is administered about 75 mg or about 150 .mg (e.g., delivered sic.). if the patient weighs -67- WO 2012/059598 PCT/EP2011/069476 54388 FF less than or equal to about 90 kg. In one embodiment, the patient is administered about 75 mg or abouf 150 mg (e.g., delivered sxc.) if the patient weighs less than or equal to about 100 kg. In another embodiment, the patient is administered about 150 mg or about 300 mg (e.g., delivered s.c.) if the patient weighs more than about 80 kg. In another embodiment, the patient is administered about 150 mg or about 300 mg (e.g., delivered -.,) if the Patient weighs morethan about 90 kg. In another embodiment, the patient is administered about 150 mg or about 300 mg (e.g., delivered s.c.) if the patient weighs more than about 100 kg. It will be understood that dose escalation may be-required (e.g., during the induction and/or maintenance phase) for certain patients, e.g., patients th at display inadequate response to treatment with the IL-17 antagonist (e;g.,secukinumab). Thus, s.c. doses of the IL-17 antagonist (e.g., secukinumab) may be greater than about 75mg toabout 360 tug sc., e.g., about 80 mg, about 100 mg; about.125 mg, about 175 tag, About 200 rug, about 250 mg, about 350 mg, about 400 mg, etc; similarly, iv doses may be greater than about 10 mg/kg, e.g., about II mg/kg, 12 mg/kg, 15 mg/kg, 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, etc. It will also be understood that dose reduction may also be required (e.g., during the induction and/or maintenance phase) for certain patients, e.g., patients that display adverse events or an adverse response to treatment with the IL-17 antagonist (e.g., secukinumab). Thus, doses of the IL-17 antagonist (e.g., secukinumab) may be less than about 75 mg to about 300 mg s.c., e.g., about 25 mg, about 50 mg, about 80 mg, about 100 mg, about 125 mg, about 175 mg, about 200 mg, 250 mg, etc.; similarly, iv. doses may be less than about 10 mg/kg, e.g., about 9 mg/kg, 8 mg/kg, 5 mg/kg, 4 mg/kg, 3 mg/kg, 2 mg/kg, I mg/kg, etc. In some embodiments of the above methods, uses, pharmaceutical compositions, kits and treatment regimens, a CRP level of > about 3 mg/L (e.g., 3 mg/L), > about 5 mg/L (e.g., 5 mg/L), > about 10 mg/L (e.g., 10 mg/L), 2 about 15 mg/L (e.g., 15 mg/L) is considered a high level of CRP. In some embodiments, a CRP level of> 200 nmol/L or > 240 nmol/L is considered a high CRP level. In a preferred embodiment, a CRP level of greater than or equal (>) to about 10 mg/L (eg., 10 mg/L), e.g., as measured by a high sensitivity CRP assay, is considered a high CRP level. In some embodiments, a high levet of CRP is > about 10 rng/L, > about 20 mg/L or > about 30 mg/L. In some embodiments of the above methods, uses, pharmaceutical compositions, kits and treatment regimens, "high ESR" may be determined based on the following rule: normal -68- WO 2012/059598 PCT/EP2011/069476 54388 FF maximum ESR (mm/h):5 (Age (years) + 10 (if female))/2, As a result, a "high ESR"> (Age (years)+ 10 (if female))/2. In some embodiments, a "high ESR" may be determined based on the following rule: normal maximum ESR (mm/h) . (Age (years) + 5 (if female))/2. As a result, a "high ESR" > (Age (years) + 5 (if female))/2. In some embodiments, an ESR of> 20 mm/h is a high ESR for females. In some embodiments, an ESR of> 15 mm/h is a high ESR for males, in a preferred embodiment, an ESR of greater than or equal (L ) to 28 mm/h is a high ESR. In some embodiments of the above methods, uses pharmaceutical compositions, kits and treatment regimens, a patient is If.+ if the patients RE value is greater than 20lU/ml or greater than 30 U/ml. In some embodimentsa patient ispbifthe patient's RF value isgreater than 40 units/ml or greater than 60 units/mIl, as measured by a nephelometry test. In some embodiments, a patient is RF+ if the patient's RF titer is greater than 1:20 or greater than [:80, as measured by a dilution test. In a preferred embodiment, a patient is RF+ if the patient's RF value is greater than or equal (> ) to 12 kU/L (kiloUnits/Liter), e.g., as measured by nephelometry. In some embodiments of the above methods, uses, pharmaceutical compositions, kits and treatment regimens, a patient is ACPA+ if the patient's ACPA value is greater than I U/ml, greater than 3 U/ml, or greater than 5 U/ml, e.g., as determined by an anti-CCP ELISA test. In a preferred embodiment, a patient is ACPA+ if the patient's ACPA value is greater than 20 units/mI (20 U). Disclosed herein are also methods of treating rheumatoid arthritis (RA), comprising a) administering (e.g., subcutaneously administering) a high risk RA patient four or five doses of about 75 mg - about 300 mg (e.g, about 75 mg.- about 150 mg, e.g., about 75 mg or about 150 mg) of an IL-17 antagonist, e.g., IL-l binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or 1L17 receptor. binding molecale (e.g., IL-17 antibody or antigen binding fragment thereof), each of the four or five doses being delivered weekly; and.b) thereafter administering about 75 mg - about 300 mg (e.g, about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg) of the IL-17 antagonist (e.g., secukinumab) to the patient twice a month, every month, every two months or every three months. Disclosed herein are also therapeutic regimens for treating RA, comprising: a) selecting a patient having rheumatoid arthritis based on the following criteria; i.) the patient is RF+, ACPA+, or both RF+ and ACPA+; and ii.) the patient has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR; and b) administering (e.g., subcutaneously administering) about 75 -69 - WO 2012/059598 PCT/EP2011/069476 5438$ FF mg - about 300 mg (eg, about 75-mg - about 150 mg e.g., about?75 mg:or about 150 mg) of an IL-1 7 antagonist, e.g., IL-17 binding molecule (e.g, IL-1 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) to the patient weekly for four or five weeks; and c) thereafter administering (e.g., subcutaneously administering) about 75 mg - about 300 mg (e.g, about 75 mg - about 150 mg, e.g., about 75mg or about 150 mg) of the IL-17 binding molecule to the patient twice a month, every month, every two months or every three months. Disclosed herein are methods of treating rheumatoid arthritis (RA), comprising administering a therapeutically effective amount of an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-i7 antibody or antigen binding fragment thereof,.e.g,, secukinumab) or IL- 17 receptor binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof) to a RA patient displaying elevated baseline CRP levels (e.g., greater than about 10 mg/L, greater than about 20 mg/L, greater than about 30 mg/L). Disclosed herein are also therapeutic regimens for treatingRA, comprising: a) selecting a patient having rheumatoid arthritis based on the following criteria:i) the. patient has elevated baseline CRP levels (e.g., greater than about 10 mg/L, greater than about 20 mg/L, greater than about 30 mg/L); and b) either i) administering (e.g., subcutaneously administering) about 75 mg - about 300 mg (e.g, about 75 mg - about 150 mg, e.g., about 75 mg or about 150 mg) of an IL 17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody orantigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) to the patient weekly for four or five doses or li) administering (e.g., i.v. administering) about 10 mg/kg of an IL-17 antagonist, e.g,, IL-17 binding molecule (e.g, IL 17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-1.7 receptor binding molecule (e.g., IL-1 7 antibody or antigen binding fragment thereof) to the patient every other week for three doses; and c) thereafter administering (e.g., subcutaneously administering) about 75 mg - about 300 mg (e.g, about 75 Mg - about 150 mg, e.g., about 75 mg or about 150 mg) of the IL-17 antagonist (e.g., secukinumab) to the patient twice a month, every month, every two months or every three months, preferably monthly. Herein are also provided methods of treating an inflammatory arthritis, comprising an induction regimen, e.g., administering (e.g., intravenously administering) two or three.induction doses of about 10 mg/kg of an IL-17 antagonist, e.g., IL-17 bindingmolecule (e;g., IL-17 - 70 - WO 2012/059598 PCT/EP2011/069476 54388 FF antibody or antigen binding fragment thereof, e.g., secokinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereo) (preferably three induction doses) to a patient having an arthritis,.wherein the arthritisis selected from the group consisting of rheumatoid arthritis (RA), spondyloarthropathy, ankylosing. spondylitis (AS), and psoriatic arthritis (PsA). In some embodiments, the first dose is delivered during week zero, the second dose is delivered during week two, and the third dose is delivered during week four. In some embodiments, the first dose is delivered during week zero, the second dose is delivered during week three, and the third dose is delivered during week six. In some embodiments, the method further comprises a maintenance regimen, e.g., administering (e.g., subcutaneously administering) about 75 mg - abouto00ng (eig, about 75 mg:- about 150 mg, e~g., about 75 mg or about 150 mg) of the IL-17 antagonist (e.g., secukinamab) to tke patient, wherein the IL-17 binding molecule is administered to the patient twice a month, monthly, every two months or every three months, In some embodiments the patient is a high risk RA patient, e.g., seropositive for rheumatoid factor (RF+), anti-cyclic citrullinated protein antibody (ACPA+), or both RF+ and ACPA+; and has a high level of C-reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a high level of CRP and a high ESR). In some embodiments, the high level of CRP is > 10 mg/dL In some embodiments, the high ESR is >28 mm/h, In further embodiments, the inflammatory arthritis is selected from rheumatoid arthritis (RA), spondyloarthropathy, ankylosing spondylitis, and psoriatic arthritis. In some embodiment,.the patient has RA. In further embodiments, the RA patient is a high risk RA patient. in further embodiments, the high risk RA patient: a) is seropositive for rheumatoid factor (RF+), anti citrullinated protein antibody (ACPA+), or both RF+ and ACPA+; and b) has a high level of C reactive protein (CRP), a high erythrocyte sedimentation rate (ESR), or both a high level of CRP and a high ESR. In some embodiments, the IL-17 antagonist, e.g., IL-I7 binding molecule (e.g,, IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) is used in combination With methotrexate for the treatment of adult patients with moderately- to severely-active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. In some embodiments, the IL-17 antagonist (e.g., secukinumab) is used alone or in combination with methotrexate or other disease-modifying anti-rheumatic drugs (DMARDs) to reduce signs and - 71 - WO 2012/059598 PCT/EP2011/069476 54388 FF symptoms (e.g., swelling, restricted movement), inducing major clinical response, inhibit the progression of structural damage, and improve physical function in adult patients with moderately to severely active disease. In some embodiments, the IL-17 antagonist(e.g., secukinumab) is used alone or in combination with methotrexate to reduce signs and symptoms, induce major elinicalresponseinhibit the progession of strutural damage, andimprove physical function inpatiets with moderately to severely activrrheumatQidarthritis (RA). In some embodiments, the IL- 17 antagonist (e.g, secukinumab) is used in combination with methotrexate, for reducing signs and symptonts, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active rheumatoid arthritis. In some embodiments, the IL-17 antagonist (e.g., secukinumab) is used for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). In some embodiments, the IL- 17 antagonist (e.g., secukinumab) is used for treating moderately to severely active Rheumatoid Arthritis (RA) in adults, in combination with methotrexate. In some embodiments, the IL- 17 antagonist (e.g., secukinumab) is used for reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients who have failed I or more disease modifying antirheumatic drugs (DMARDs). In some embodiments, the IL- 17 antagonist (e.g., secukinumab) is used as a monotherapy or concomitantly with disease-modifying antirheumatic drugs (DMARDs) for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. In some embodiments, the IL-17 antagonist (e.g., secukinumab) is used alone or in combination with methotrexate or other DMARDs to treat adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies. Combination Therapies for the Treatment of Arthritis In practicing the methods of treatment or uses of the present disclosure, a therapeutically effective amount of an IL-1 7 antagonist, e.g., IL-17 binding molecule (e.g., IL-1 7 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) is administered to a subject, e.g, a mammal (e.g., a human). An IL- 17 binding antagonist (e.g., secukinumab) may be administered in - 72 - WO 2012/059598 PCTIEP2011/069476 54388 FF accordance with the method ofthe disclosure either aone ot in oibination with other agents and therapies for treating RA, e.g., in combination with at least one anti-rheumatic agent, such as an immunosuppressive agent, a disease-modifying anti-rheumatic drug (DMARD), a pain control drug, a steroid, a non-steroidal anti-inflammatory drug (NSAID), a cytokine antagonist, a bone anabolic, a bone anti-resorptive, and combinations thereof (e.g,, dual and tripple therapies). When coadministered with one or more additional agents, an IL-17 antagonist (e.g., secukinumab) may be administered either simultaneously with the other agent, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering the IL-1 7 antagonist (e.g., secukinumab) in combitiation with other agents Non-steroidal anti inflammatory drugs and pain control agents useful in combination with the IL-17 antagonist (e.g., secukinumab) for the treatment of RA patients, e.g., high risk RA patients, include, propionic acid derivative, acetic acid derivative, enolic acid derivatives, fenamic acid derivatives, Cox inhibitors, e.g., lumiracoxib, ibuprophen, fenoprofen, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, aspirin, naproxen, valdecoxib, etoricoxib, MK0966; rofecoxib, acetaminophen, Celecoxib, Diclofenac, tramadol, piroxicam, meloxicam, tenoxicami droxicam, lornoxicarn isoxicam,-mefanamic acid, meclofenamic acidflufenamic acid, tolfenamic, valdecaxib, parecoxib, etodblac, indomethacin, aspirin, ibuprophen, firocoxib. Disease-modifying antirheumatic drugs (DMARDs) useful in combination with the IL-17 antagonist (e.g., secukinunab) for the treatment of RA patients, e.g., high risk RA patients, include, methotrexate (MTX), antimalarial drugs (e.g., hydroxychloroquine and chloroquine), sulfasalazine, Leflunomide, azathioprine, cyclosporin, gold salts, minocycline, cyclophosphamide, D-penicillamine, minocycline, auranofin, tacrolimus, myocrisin, chlorambucil. Biologic agents useful in combination with the IL-17 antagonist (e.g., secukinumab) for the treatment of RA patients, e.g., high risk RA patients, include, ADALIMUMAB (Humira@), ETANERCEPT (Enbrel@), INFLIXIMAB (Remicade®; TA-650), CERTOLIZUMAB PEGOL (Cimzia@; CDP870),GOLIMUMAB (Simponi@; CNTO148), ANAKINRA (Kineret@), RITUXIMAB (Rituxan@; MabThera@), ABATACEPT (Orencia®), TOCILIZUMAB (RoActemra /Actemra@). -7.3 - WO 2012/059598 PCT/EP2011/069476 54388 FF Other biological agents useful in combination with the IL-17 antagonist (e.g., secukinumab) for the treatment of RA patients, e.g., high risk RA patients, include, e.g., integrin antagonist (TYSABR(@ (natalizumab)), IL-I antagonists (ACZ885 (llaris)), Anakinra (Kineret@)), CD4 antagonists,. IL-l 7 antagonists (LY2439821, RG4934, AM0827, SCH900117, R05310074, MEDI-57 1, CAT-2200), IL-23 antagonists, IL-20 antagonists, IL-6 antagonists, TNF alpha antagonists (e.g., TNF alpha antagonists or TNF alpha:receptor antagonsits, e.g., pegsunercept, etc.), BLyS antagonists (e.g,, Atacicept,: Bn lysta@/ LymphoStat"B@ (belimumab)), P38 Inhibitors, CD20 antagonists (Ocrelizumab, Ofatumumab (Arzerra®)), Interferon gamma antagonists (Fontolizumab) Steroids (e.g., glucocorticoids) useful in combination with the IL- 17 antagonist (e.g., secukinumab) for the treatment of RA patients, e.g., high risk RA patients, include, Prednisolone, Prednisone, dexamethasone, cortisol, cortisone, hydrocorfisone, nethyiprednisolone, betamethasone, triamcinolonebedlometasome, fludrocottisona, deoxycorticosterone, aldosterone Other agents useful in combination with the IL-17 antagonist (e.g., secukinumab) for the treatment of RA patients, e.g., high risk RA patients, include,SB-681323, Rob 803, AZD5672, AD 452, SMP 114, HZT-501, CP- 195,543, Doxycycline, vancomycin, CRx-102, AMG108, pioglitazone, SBI-087, SCIO-469, Cura-100, Oncoxin + Viusid, TwF, PF-04171327, AZD5672, Methoxsalen, ARRY-438162, Vitamin D - ergocalciferol, Milnacipran, Paclitaxel, GW406381, rosiglitazone, SC12267 (4SC-101); LY2439821, BTT-1023, ERB-041, ERB-041, KB003, CF101, ADL5859, MP-435, ILV-094, GSK706769, GW856553, ASK8007, MOR103, HE3286, CP-690,550 (tasocitinib), REGNB8 (SARI 53191), TRU.015, BMS-582949, SB1-087, LY2127399, E-55 IS-55 1, H-551, 0SK3152314A, RWJ-445380, Tacrolimus (Prograf@), RADOO1, rapamune, rapamycin, fostamatinib, Fentanyl, XOMA 052, CNTO 136, JNJ 38518168, Imatinib, ATN-103, [SIS 104838, folic acid, folate, TNFa kinoid, MM-093, type I collagen, VX-509, AMG 827 70, masitinib (AB 1010), LY2127399, cyclosporine, SB-681323, MK0663, NNC 0151-0000-0000, ATN-103, CCX 354-C, CAM300.I, LX3305, Cetrorelix, MDX-1342, TMI-005, MK0873, CDP870, Tranilast, CF101, mycophenolic acid (and esters thereof), VX-702, GLP00259, S3-681323, BG9924, ART621, LX3305, T-614, Fostainatinib disodiuni (R935788), CC-779, ARRY-371797, CDP6038, AMG719, BMS-582949, GW856553, rosiglitazone, CH 4051, CE-224,535, GSK1827771, 0W274150, BG9924, PLX3397, TAK-783, INCB028050, LY2127399, LY3009104, R788, Curcumin (Longvidar"), Rosuvastatin, PR0283698, AMG 714, - 74 - WO 2012/059598 PCT/EP2011/069476 54388 FF MTRXI01 lA, Maraviroc, MEDI-522, MK0663, STA 5326 nesylate, CE-224,535, AMG108, BG00012, ramipril, VX-702, CRx-102, LY2189102, SBI-087, SB-681323, CDP870, Milnacipran, PD 0360324, PH-797804, AK.106-001616, PG-760564, PLA-695, MK0812, ALD51 8, Cobiprostone, somatropin, tgAAC94 gene therapy vector, MK0359, GW856553, esomeprazore, everolimus, trastuzinmab, bone anabolics and bone anti-resorptives (e.g, PTH, bisphosphonates (e.g., zoledronic acid), JAKI and .JAK2 inhibitors, pan JAK inhibitors, eg., tetracyotic pyridone 6 (P6), 325, PF-956980, sclerostin antagonists (e g., disclosed in W009047356, W02000/32773, WO2006102070, US20080227138, US20100028335, US 20030229041, W02005003158, W02009039175 W02009079471, W003106657, W02006119062, WO08115732, W02005/014650, W02005/003158, W02006/119107, W02008/061013, W02008/133722, W02008/115732, U7592429, US7879322, US7744874, the contents of which are incorporated by reference herein in their entirety [preferred anti sclerostin antibodies and antigen binding fragments thereof for use in the disclosed methods, pharmaceutical compositions, kits and uses are found in W009047356 (equivalent to US7879322), W0061 19107 (equivalent to US7872106 and US 7592429) and WOOS 115732 (equivalent to US7744874]), denosumab, IL-6 antagonists, CD20 antagonistis, CTLA4 antagnonists, IL-I 7 antagonists, IL-8 antagnoists, IL-21 antagonistis, IL-22 antagonist, integrin antagonists (Tysarbri@ (natalizumab)), scleronstin antagonists, VGEF antagnosits, CXCL antagonists, MMP antagonists, defensin antagonists, IL-1 antagonists (including IL-I beta antagonsits), and IL-23 antagonists (e.g., receptor decoys, antagonistic antibodies, etc.). In some embodiments, the iL-I 7 antagonist (e.g., secukinunab) is admininistered in combination with-at least one anti-rheumatic agent selected from the goupconsisting of an immunosuppressive agent, a DMARD, a pain-control drug, a steroid, a NSAID, a cytokine antagonist, a bone anabolic, a bone anti-resorptive, and combinations thereof. In some embodiments, the IL-17 antagonist (e.g., secukinumab) is admininistered in combination with a TNF antagonist, a DMARD (e.g., MTX, e.g., weekly doses of 7.5 -30 mg)), a steroid, or combinations thereof. A skilled artisan will be able to discern the appropriate dosages of the above agents for co-delivery with the IL-17 antagonist (e.g., secukinumab). - 75 - WO 2012/059598 PCT/EP2011/069476 54388 FF Kits and Africs of Manufacture Disclosed herein are kits (i.e., an article of manufacture) useful for providing an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-Il antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptorbinding molecule (e.g., IL-17 antibody or antigen binding fragment thereof), for the treatment of RA. Such kits may comprise an IL-l7 antagonist (e.g., secukinumab) (e.g., in liquid or Jyophilized form) or a pharmaceutical composition comprising the IL-17 antagonist (e.g., secukinumab). Additionally, such kits may comprise means for administering the IL-17 antagonist (e.g., secukinumab) (e~g., a syringe or a prefilled pen) and instructions for use. These kits may contain additional therapeutic agents (described supra) for treating RA, e.g., for delivery in combination with the enclosed IL-17 antagonist (e.g., secukinumab). Disclosed herein are kits comprising: a) an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof); b) instructions for administering the IL-I7 antagonist (e g., secukinumab), to a high risk RA patient; c) means for administering the IL- 17 antagonist {b.g., secukinumab) to the patient; and d) optionally, a therapeutically effective amount of at least one anti-rheurnatic agent selected from the group consisting of an immunosuppressive agent, a disease-modifying anti-rheumatic drug (DMARD), a pain-control drug, a steroid, a non-steroidal anti-inflammatory drug (NSAID), a cytokine antagonist, a bone anabolic, a bone anti-resorptive, and combinations thereof, In some embodiments the high risk RA patient: a) is RF+, ACPA+, or both RF+ and ACPA+; and b) has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. Disclosed herein are kits comprising: a) an IL-17 antagonist, e.g,, IL-17 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), or IL-I7 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof) or a pharmaceutical composition comprising an IL-17 antagonist, for use in the treatment of rheumatoid arthritis (RA) in a patient; and b) instructions describing how to administer said pharmaceutical composition to the patient, wherein the patient is characterized as: i) being RF+, ACPA+, or both RF+ and ACPA +; and ii) having a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. -76 - WO 2012/059598 PCTIEP2011/069476 54388 FF Also disclosed herein are. in vitro test methods for selecting a patient for treatment of RA, comprising determining if: i. the patient is RF+, ACPA+, or both RF+ and ACPA+; and ii. the patient has a high level of CRP, a high ESR, or both a high level of CRP and a high ESR. In some embodiments of the test method, the patient is expected to have an improved therapeutic response to the following regimen: a) either i) administering the patient three doses of about 10 mg/kg of an IL-17 antagonist, e.g., IL-l7 binding molecule (egg., [L-1 7 antibody or antigen binding fragment thereof, e.g., secukinumab), or IL-17 receptor binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof), the first dose being. delivered during week zero, the second dose being delivered during week two, and the third dose being delivered during week four or ii) administering the patient weekly doses of about 75 mug or about 150 mg of an IL-1 7 antagonist, e.g., IL-17 binding:molecule (eg., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab), or IL-17 receptor binding.molecule (e.g., IL-17 antibody or antigen binding fragment thereof) for four or five (preferably five) doses; and b) thereafter administering the patient about 75 mg - about 300 mg of the IL-17 antagonist twice a month, monthly, every two months or every three months (preferably monthly), beginning during week eight. These in vitro methods may be performed on biological samples (e.g.., blood, cartilage, bone, serum,.etc.) extracted from the patient and may be used in determining the mode or course of treatment for a particular patient, e.g., whether to administer the IL- 17 antagonist to the patient (alone or in combination with another compound, e.g., such as methotrexate), or whether to choose alternative therapies (e.g., anti-TNF treatment). Diagnostic Methods and Methods of Producing a Transmittable Form of Information Disclosed herein are methods for determining (predicting) the likelihood that an RA patient will respond favorably (e.g., reduced sign and symptoms, reduced joint damage, increased quality oflife, etc.) to treatnentwith an an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL-I7 antibody orantigen binding fragment thereof, e~g., secukinumab) or IL-17 receptor binding molecule (e.g., IL- l7antibody or antigen binding fragment thereof). Such methods will help physicians determine a course of treatment for a particular RA patient, Disclosed herein are also methods of determining the likelihood that an RA patient will respond to treatment with an an IL-17 antagonist, e.g., IL-I 7 binding molecule (e.g., IL-17 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL-17 receptor binding - 77 - WO 2012/059598 PCT/EP2011/069476 54388 FF molecule (e.g., IL-17 antibody or antigen binding fragment thereof), comprising assaying a sample from the patient for: a) rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and b) C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR, wherein the patient is likely to respond to treatment of RA with the IL- 17 antagonist (e~g, secukinumab) if the patient'is RF+, ACPA 4, or RF+ and ACPA +; and the patient has aihigh level ahigh ESkor high level ofCRP and a high.SR then the patient. in some embodiments, pror to thecstep.of assaying, a sample is-first obtained from the patient (e.g., by extracting blood or other biological tissue from the patient), Disclosed herein are also methods of predicting the likelihood that an RA patient will respond to treatment with an an [L-i 7 antagonist, eig., IL-17 binding molecule (e.g., IL-1 7 antibody or antigen binding fragment thereof, e.g., secukinumab) or IL- I7 receptor binding molecule (e.g., IL- 17 antibody or antigen binding fragment thereof) comprising, determining whether a patient: a) is RF+ and/or ACPA; and 2) has a high level of CRP and/or a high ESR, wherein the patient has an increased likelihood or responding to treatment with the IL-l7 antagonist if the patient is RF+, ACPA +, or RF+ and ACPA +; and has a high level of CRP, a high ESR, or a high level of CRP and a high ESR. In some embodiments, prior to the step of determining, a sample is first obtained from the patient (e.g., by extracting blood or other biological tissue from the patient). Disclosed herein are also methods of determining the likelihood that an RA patient will respond to treatment with an an IL-17 antagonist, e.g., IL-17 binding molecule (e.g., IL- 17 antibody or antigen binding fragmentitherecf, e.g, secukoinutnab) or IL- 17 receptor binding molecule (e.g. IL-17 antibody or antigen binding fagmeit thereof comprising, assaying.a sample from the patient for the baseline level of C-reactive protein (CRP), wherein the patientAis likely to respond to treatment of RA with the IL-17 antagonist (e.g., secukinumab) if the patient has elevated baseline CRP. In some embodiments, prior to the step of assaying, a sample is first obtained from the patient (e.g., by extracting blood or other biological tissue from the patient). For these diagnostic and prognostic methods, a sample from the patient may be assayed by any conventional means for detecting the factor (RF, ACPA , CRP, ESR) or level of factor, e.g., radial immrunodiffusion, electroimmunoassay, immunoturbidimetry, Western blot, Norther blot, ELISA, turbidimetric methods, fluorescence polarization immunoassay, laser nephelometry, an agglutination test, a nephelometry test, measuring the distance that red blood cells precipitate -78 - WO 2012/059598 PCT/EP2011/069476 54388 FF in a tube over time (e.g., in the case of BSR), etc. The terms. assaying" and "determining" contemplate a transfonnation of Matter; e.g., a transformation of a biological sample, e.g, a blood sample or othertissue sample, from one.statetonother by means ofsubjectingthat sample to physical testing. Further, as used herein, the terms "assaying" and "determining" are used to mean testing and/or measuring. The phrase "assaying a sample from the patient for.." and the like is used to mean that a sample may be tested (either directly or indirectly) for either the presence or nonpresence of a given factor or for the level of a particular factor. It will be understood that, in a situation where the presence of a substance denotes one probability and the absence of a substance denotes a different probabitity, then either the presence or the. absence of such substance may be used to guide a therapeutic decision. In some embodiments, prior to treatment with the IL-i 7 antagonist, askilled clinician will determine whether a patient is a high risk RA patient. Typically, once the presence or absence of a particular factor, or the level of a particular factor is identified, physicians or genetic counselors or patients or other researchers may be informed of the result. Specifically, the result can be cast in a transmittable form of information that can be communicated or transmitted to other researchers or physicians or genetic counselors or patients. Such a form can vary and can be tangible:or intangible The result with regard to the presence or absence of RE and/or ACPA, and/or the levelof CRp and/or ESR in the individual tested can be embodied in descriptive statements, diagrams, photographs, charts, images or any other visual forms. For example, images of gel electrophoresis of PCR products can be used in explaining the results. The statements and visual forms can be recorded on a tangible media such as papers, computer readable media such as floppy disks, compact disks, etc., or on an intangible media, e.g., an electronic media in the form of email or website on internet or intranet. In addition, the result with regard to the presence or absence of RF and/or ACPA, and/or the level of CRP and/or ESR in the individual tested can also be recorded in a sound form and transmitted through any suitable media, e.g., analog or digital cable lines, fiber optic cables, etc., via telephone, facsimile, wireless mobile phone, internet phone and the like. All such forms (tangible and intangible) would constitute a "transmittable form of information", Thus, the information and data on a test result can be produced anywhere in the world and transmitted to a different location. For example, when a genotyping assay is conducted offshore, the information and data on a test result may be generated and cast in a transmittable form as described above. -79- WO 2012/059598 PCT/EP2011/069476 34388 FF The test result in a transmittable form thus can be imported into the U.S. Accordingly, the present disclosure also encompasses a method: for producing a transmittable form of information on the presence or absence of RF and/or ACPA, and/or the level of CRP and/or ESR n a individual. Disclosed herein are methods for producing a transmittable form of information on a patient having RA, comprising: a) assaying a sample from the patient for: i)-rheumatoid factor (RF), anti-citrullinated protein antibody (ACPA), or RF and ACPA; and ii) C-reactive protein (CRP), an erythrocyte sedimentation rate (ESR), or both CRP and an ESR; and b) embodying the result of the assaying step in a transmittable form of information, In some embodiments, followingthe step of ombodying, aeaith care provider (e.g.,.physician) uses the transmittable form of information in making a decision to prescribe one of the treatment regimens disclosed herien, using the IL-17 antagonists disclosed herein. In some embodiments, following the step of embodying, a health care provider (e.g., physician) administers an IL-17 antagonist to the patient if the transmittable form of information identifies the patient as a high risk RA patient. General All patents, published patent applications, publications, references and other material referred to herein are incorporated by reference herein in their entirety.The details of one or more embodiments of the disclosure are set forth in the accompanying description above. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, the preferred methods and materials are now described. Other features, objects, and advantages of the disclosure will be apparent from the description and from the claims. In the specification and the appended claims, the singular forms include plural referents unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by orreof ordinary skill in the art to which this disclosure belongs. All patents and publications cited in this specification are incorporated by refrence. The. following Examples are presented in order to more fully illustrate the preferred embodiments of the disclosure. These examples should in no way be construed as limiting the scope of the disclosed patient matter, which is defined by the appended claims. - 80 - WO 20121059598 PCT/EP2011/069476 54388 FF EXAMPLES Example 1; Use of secukinumab to treat rheumatoid arthritis (RA) (CAIN457F2201) Example 11 - Study Design The study population consists of a representative group of patients (male or non" pregnant, nonlactatin fermles) of at least 18 years of age; fulfilling ACR 987 revised classification criteria for RA for d least 3 months. Eligible patients were required to present active RA defined by 26 out of 28 tender joints and 6 out of 28 swollen joints, and hsCRP 210 mg/L OR ESR >28 mm/tst hour (mm/h) at the time of randomization to assure ability to detect response to treatment using ACR criteria. Eligible candidates were on MTX for at least 3 months and at selection were currently treated with a stable weekly dose of MTX ( 7.5 mg/week - 525 mg/week) for at least 4 weeks. Adult RA patients (n=237) on methotrexate were randitmized equally to receive monthly s.c. injections of secukinumab 25mg, 75mg, 150mg, 300mg or placebo. Patients with previous exposure to biologics were included in all cohorts (18 - 22%). The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 at week 16, At Week 20 (Visit 8), patients who were randomized to placebo at Week 0 or who were randomized to secukinumab but did not achieve an ACR20 response at Week 16 were re-assigned to receive double blind treatment up to Week 48, with a final efficacy assessment performed at Week 52, and a follow up visit at Week 60, as follows starting at Week 20 (Figure 1): " Patients on active treatment who were responders continued on their dose regimen; " Al] placebo patients were switched to active treatment 150 mg sec, q4wk (monthly), independent of disease activity; " All patients treated with 25 mg or 75 mng secukinumab q4wk who were non-responders were switched to 150 mg s.c. q4wk; " Non-responders in the 150 mg group were switched to the next highest dose - 300 mg s.c. q4wk; * All patients on 300 mg group remained on their respective dose to assess if exposure longer than 16 weeks will induce a clinical response in these patients. Efficacy assessments are ACR20, 50, 70 (Felson et al. (1995) Arthritis Rheum; 38(6):727 35) and DAS28 response/remission (Fransen et al (2003) Ann Rheum Dis; 62(Suppl 1): 10; -81t - WO 2012/059598 PCT/EP2011/069476 54388 FF Prevoo et al. (1995) Arthritis Rheum; 38(J):44-4). The.primary efficacy variable is the clinical response to treatment according to ACR20 individual -imptovement in disease activity at Week 16. Results are assessed by the proportion of patients achieving the ACR20 response criteia at Week 16. A patient will be considered a responder according to ACR20 criteria if he/she has: A) at least 20 % improvement in the two following measures: - tender 28-joint count - swollen 28-joint count; and B) at least 20 % improvement in at least 3 of the following 5 measures: * Patient's assessment of RA pain (VAS 100 mm) * Patient's global assessment of disease activity (VAS 100 mm) - Physician's global assessment of disease activity (VAS 100 mm) - Patient self-assessed disability (Health Assessment Questionnaire [HAQC] score) - Acute phase reactant (C-reactive protein [hsC.RP) or erythrocyte sedimentation rate (ESR)) Additional measures include: ACR50 (50 % improvement in item B (above) ii at least 3 of the 5 measures and 50 % improvement in the swollen and tender joint count) and ACR70 (70 % improvement in item B (above) in at least 3 of the 5 measures and 70 % improvement in the swollen and tender joint count). The DAS28 (Disease Activity Score -28) is a well-established measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the number of tender and swollen joints (out of a total of 28), the erythrocyte sedimentation rate (ESR) or hsCRP, and the patient's global assessment of global health (indicated by marking a 100 mm line between very good and very bad). A DAS28 score greater than 5.1 implies active disease, less than 3.2 well controlled disease, and less than 2.6 remission, In order to calculate the DAS28, information about the following disease variables is needed: - The number of swollen joints and tender joints should be assessed using 28-joint count (tender28 and swollen28). ' The erythrocyte sedimentation rate (ESR) should be measured in mm/hour. - The patient's general health (GH) or global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm (both are useable for this purpose) must be obtained. Using this data, the DAS28 can be calculated using the following formula: - 82 - WO 2012/059598 PCT/EP2011/069476 543&8 FF DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * In(ESR)+0.014 *.GH C-reactive protein (CRP) may be used as an alternative to ESR in the calculation of the DAS or DAS28, using the formulas below. CRP is a more direct measure of inflammation than ESR, and it is more sensitive to short-term changes. CRP production is associated with radiological progression in RA, and is considered at least as valid as ESR to measure RA disease activity. Another advantage of determination of CRP is that waiting time for the laboratory result is shorter and that in case of multicenter studies a central laboratory can be used. The following formulas to calculate the DAS28 using CRP (mg/L) give good estimations of the original DAS28 values on a group level. DAS28-4(crp) = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.0 14*GH + 096 TJC28: 28 Tender joint count; SJC28: 28 Swollen joint count; CRP: C-reactive protein; GH: General Health on a 100Nm. Visual Analogue Scale. The HAQ© is a validated measure of physical disability and functional status. It has four dimensions: disability, pain, drug side effects and dollar costs, although, the latter three are rarely used in clinical trials. In this trial only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing eight common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Subjects choose from four response categories, ranging from 'without any difficulty' to 'unable to do'. The ACR Rheumatology Committee on Outcome Measures in RA recommends the use of this questionnaire in clinical trials. The HAQ© is scored in accordance with the recommendation from the developers outlined in the "HAQ PACK" from. Stanford University, California. Example 1.2- Statistical Analysis To test superiority of secukinumab treatment groups over placebo, the ACR20 responder rate (proportion) was compared against placebo for each of the secukinumab-treated groups based on a logistic regression model with treatment, center and baseline DAS28 as covariates. -83 - WO 2012/059598 PCT/EP2011/069476 54388 FF The DAS28-CRP change from baseline was analyzed using an analysis of covariance (ANCOVA, SAS PROC MIXED) fixed effects model with treatment as main effect and correcting for the covariates center and baseline value. All statistical tests for pairwise comparisons of secukinurnab treatment groups vs placebo were performed at two-sided 5% significance level. The method of last observation carried forward (LOCF) was used for missing values for efficacy variables. Figures were produced presenting response over time or at specific time points up to Week 16 (or Week52, as appropriate Otnate, for fgures-presentng results up to Week 52 only data from patients continuing at Week 24 were included. The full analysis set (PAS) was used for the reporting of the efficacy results. The FAS comprised all patients to whom study drug had been assigned. Following the intent-to-treat (ITT) principle, patients were analyzed according to the treatment and stratum they were assigned to at randomization. Example 1.3 - Week 16 Results Demographics and baseline characteristics were comparable across all groups. ACR20 responders at Week 16 were higher in the secukinumab 75mg, 150mg and 300mg dose groups (46;9%, 46.5% and 53.7%, respectively) compared to :placebo (36.0%) and compared to secukinumab 25mg (34%) (Figure 2A). However, these results did not achieve statistical significance due to a marked and unexplained increase in ACR20 in the placebo group between Week 12 (24%) and 16 (36%). Clinically relevant reductions in DAS28-CRP were observed in the secukinumab 75-300mg treatment groups vs. placebo (Figure 5A). Serum CRP levels at Week 16 were markedly reduced in secukinunab 75-300mg groups vs. placebo (p= 0.0012, 0.0081 and 0.0241) (data not shown). ACRSO and ACR70 showed consistent greater improvements with secukinumab 75-300mg doses vS. placebo over 16 weeks (Figures 3A and 4A). There was about a 4-fold average reduction from baseline in the HAQO score at week 16 in the 150-300 mg groups compared to placebo (Figure 6A). Example 1.4 - Week 24 Results By Week 24, ACR20 responses were maintained and DAS28 CRP responses further improved in the 75-300 mg groups with secukinumab treatment between week 16 and 24. HAQ© scores were either maintained or father reduced in the 75 - 300 mg groups with groups with secukinumab treatment between week 16 and 24. The 75 - 300 mg ACR20 responder -84 - WO 2012/059598 PCT/EP2011/069476 54398FF treatment groups exhibited an early improvement in HAQC scores over time through Week 24. ACR50 responses further improved from 19 - 24% (75 mg), 21 - 25% (150 mg) and 19 - 24% (300mg) in patients originally randomized to the respective dose cohorts, part of whom had a dose escalation at Week 20; a similar improvement was seen in ACR70 responses in the 75 mg 150 mg groups. An increase in the ACR20/50/70 response in the patients randomized to placebo between Week 16 and 24 can also be noted. All patients on placebo up to Week 16 were switched to secukinumab 150 mg at Week 20. Example 1.5 - Week 52 Results With respect to efficacy of secukinumab over time patients who had been responders at week 16 generally maintained their responses in terms of ACR 20 (Figure 2C), ACR50 (Figure 3B) and ACR70 (Figure 4B) with best responses seen in the 150 mg responder cohort. The same was also true for DAS28-CRP and HAQ scores reponses which were maintained in responders at week 16 over time through week 52 again with best responses observed in the 150 mg responder cohort (Figure. 5B, 6B). ACR20, 50 and. 70 responses at week 52 are shown in Figure 7 again with highest responses for all these parameters in the 150 mng responder cohort, Biological failure patients were 18-22% in each cohort at study start. Of patients previously exposed to biologics who were dosed with 150 mg secukinumab after Week 20, 62% (8 of 13) achieved an ACR20, 38% (5 of 13) achieved an ACR50 and 23% achieved an ACR 70 at Week 52. This provides evidence that secukinumab is capable of treating RA in patients who failed anti-TNF and other biological therapy. Example 2: Analysis of High Risk RA Patient Subset in CAIN457F2201 Example 2.1 - Statistical Analysis In searching for indicators predictive of an RA patient's response to treatment with secukinumab, we analyzed two of the four 2010 ACR/EULAR scoreable criteria (see Table 1) to determine how (and whether) these criteria may influence response to treatment with secukinumab with data from the CAIN457F220 1 trial database.. First, we analyzed serology to determine whether the patient is RF + and/or anti-CCP + (i.e., ACPA +). Second, we analyzed the presence of acute-phase reactants to determine whether the patient has a high level of C reactive protein (CRP) and/or a high erythrocyte sedimentation rate (ESR). - 85-_ WO 2012/059598 PCT/EP2011/069476 54388 FF Analysis was mainly performed with summary statistics (proportions for binary response variables and average for continuous variables) produced over time to observe responses up to Week 16 (or 52, for patients who continued at Week 24). The method of last observation carried forward (LOCF) was used for missing values for efficacy variables. Data were produced presenting response over time or at specific time points up to Week 16 (or Week 52, as appropriate). Of note, for data showing results up to Week .52, only data from patients continuing at Week 24 were included. Example 2.2 - Analysis of responses to secukinumab in high risk RA patients The analysis of subgroup of patients with "high risk" (i.e., "high risk RA patients") for disease progression (based on high CRP and/or ESR; and positive:RF and/or ACPA).showed promising results in the secukinurnab treated patients compared to the CAIN457F220 I overall trial results, while the responses in the placebo group did not show similar increased trend. In terms of ACR20, in the FAS, 46.9, 46,5, $37 and 36 % response was observed at Week 16 in the secukinumab 75, 150, 300 mg and placebo (Figure 2A and Table 6), respectively, whereas 48,8, 57,6, 58.1 and 4 1.0 % responses was observed at Week 16 in the high risk subgroup (Figure 2B and Table 6). Similarly, increased response rates were observed at Weeks 16 and 52 in the high risk subgroup compared to the FAS, and in other variables such as ACR50/70 (Table 6), DAS28-CRP (Table 7), and HAQ© (data not shown). Summaries of ACR20/50/70 % and DAS28-CRP responses at weeks 16 and 52 in the FAS, the high risk RA patients, and the non-high risk RA patients are provided in Table 6 (ACR) and Table 7 (DAS28-CRP). Graphical depiction of the ACR20/50/70 % and DAS28 CRP responses at week 16 in the high risk PA patients and the non-high risk RA patients are provided in Figures 8A and 8B. ACR Responses Week 16 Placebo 25,mg 75 mg 150 mg 300 mg FAS ACR20 18/50 (.36.0%) 1/3334.0%) 23/49(46,9%) 20/43(465%) 22/41 -53.7%) ACR50 3/50(6.0%) $/53 (15_1%) 9/49(114%) 9/43(209%) 7/41 (17.1) ACR70 0/50 (0.0%) 4/53 (7.5%) 1/49 (2.0%) 2/43 (437%) .2/41 (4.9%) High risk RA ACR20 16/39 (41.0%) 15/44 (34.1%) 21/43 (48.8%) 19/33 (57.6%) 18/31 (5& 1%) patient ACR50 2/39 (5.1%) 7/44 (15.9%) 8/43 (18.6%) 8/33 (24.2%) 5/31 (16.1%) - 86.- WO 2012/059598 PCT/EPZOI1/069476 54388 FF subgroup ACR70 0139 (0.0%) 3/44(6.8%) 1/43 (2.3%) 2/33 (6.1%) 1/31 (3.2%) Non High risk ACR20 2/11 (18.2%) 3/9 (313%) 2/6 (33.3%) 1/10 (10.0%) 4/10, (40.0%) RApatient ACIR50 1/1 (9.1%) 1/9(11.1%) 1/6(167%) 1/10(10.0%) 2/10(20.0%) subgroup ACR7O 0/11 (0.0%) 1/9(1.1%) 0/6 (0.0%) 0/10 (0.0%) 1/10 (10.0%) Week 52 Placebo .25mg '5 ni . 150 mg 300-mg FAS ACR20 27/44(61.4%) 18/45 (40d%) 26/46 (6;5%) 26/43 (60.5%) 17/37 (45.9%) ACR50 17/44-(31.60/) 5/45.(113%) 13/4 (28.3%) 13/43 (30.2%) 5/37(13,5%) ACR70 5/44(t1.4%) 2/45 (44%) 5/46 (10/9%) 4/43(9.3%) 3/37(8.1%) High risk RA ACR20 22/33 (66.7%) 18/38(47:4%) 20/40 (500%) 24/33 (72.7%) 12/28 (42.9%) patient ACR50 14/33 (42,4%) 4/38 (10.5%) 11/40 (27.5%) 13/33 (39-.4%) 5/28 (17.9%) subgroup ACR70 5/33 (15.2%) 2/38(5,3%) 4140 (10.0%) 10/33 (30.3%) 2/28(7,1%) Non High risk ACR20: 5/11 (45.5%) 3/7 (42.9%) 316 (50.0%) 3/10 (30.0%) 4/9 (44,4%) RA patient ACR50 3/1 1(27.3%) 1/7(14,3%) 2/6 (33.3%) 1/10(10.0%) 319(333%) subgroup ACR70 0/11(0.0%) 1/7(14.3%) 1/6(16.7%) 0/10 (0:0%) 1/9(11.1%) Table 6: ACR responses (LOCF) at weeks 16 and 52 in FAS, highrisk RA patients, and non high risk RA patients, Median change from baseline in DAS2S-ESR Week 16 Placebo 25 mg 75 mg 150 mg 3O0 mg FAS -0.97 -0.84 -1.40 -1.23 -1.38 High risk RA patient subgroup -1.00 -0.65 -1.22 -1.81 -1.23 Non High risk RA patient subgroup -0U8 -1.17 -1.33 -0.27 -0.77 Week 52 Placebo 25 mg 75 mg 150 mg 300 mg FAS -168 -1.31 -] 1 -219 -1.33 High risk RA patient subgroup -2:00 -1.33 -1.51 -2.87 , 136 Non High risk RA patient subgroup -1,07 -1.11 -1.40 -1.43 4.29 Table 7: DAS28-ESR median change from baseline at weeks 16 and 52 in FAS, high risk RA patients, and non high risk RA patients. Note, for Table 6 and 7, week 52 data is presented by the original assigned treatment. Titration was performed for ACR20 non-responders (and all placebo patients) starting at week 16. 18/45 'original' 25 mg patients remained on 25 mg while 27 patients were up-titrated to 150 mg. Likewise, 23/46 'original' 75 mg patients remained on 75 mg while 23 were up-titrated to 150 mg. 20/43 'original' 150 mg patients remained on 150 mg and 23 were up-titrated to 300 -87- WO 2012/059598 PCT/EP2011/069476 54388 FF mg. All 44 'original' ilacebopatients were switched to 150 mg:and all 'original' 300 mg patients remained on 300 mg. As can be seen from Tables 6 and 7, as well as Figures 8A and 8B, high risk RA patients generally display an improved response to IL-17 inhibition in comparison to non-high risk. RA patients. Comparing the ACR20% and ACR50% response between the high risk RA patients and non-high risk RA patients at week 16 (Table 6 and Figure SA), a dose response can be seen in the high risk RA patients in response to IL-17 inhibition by secukinunab. A similar dose response is seen in the DAS28-CRP score in high risk RA patients at weeks 16 and 52 (Table 7 and Figure SB). Futhermore, ACR20% responses at week 16 inthe high risk RA patient subset are improved at all doses of secukinumab above 25 mg in comparison to the ACR20% responses seen in non-high risk RA patients (Table 6 and Figure SA). In addition, the ACR50/70% response at weeks 16 and 52 in high risk RA patients treated with 150 mg secukinumab is higher than the ACR50/70% response in noa-high risk RA patients treated with the same secukinumab dose. A similar result is seen in the DAS28-CRP score for 150 mg secukinumab at weeks 16 and for all doses of secukinumab at week 52 (Table 7 and Figure 8B). Example 3: Patients with Elevated Baselle CRP Benefit from Seeukinunab Example 33 - Study Design To evaluate the dose-response relationship of DAS28 and ACR responses &t-week 16 by baseline high sensitivity (hs) CRP levels in patients with RA treated with different doses of secukinumab compared to placebo. As described previously, in study CA1N457F2201, adult RA patients (n=237) on methotrexate were randomized to receive monthly s.c. injections of secukinumab 25mg, 75mg, 150mg, 300mg, or placebo. We assessed dose relationship of DAS28 and ACR responses at week 16 by different baseline hsCRP levels (20mg/L, 1Omg(L, 20mg/L, and >30mg/L). Example 3.2 - Results Demographics and baseline characteristics were comparable across all groups. A rapid reduction in DAS28-CRP was observed as early as week 2 in patients on secukinumab 75 mg, 150 mg, 300 mg groups. By week 12, these patients achieved a clinically meaningful DAS28 reduction of> L.2 compared with those on placebo (P<0.05). These responses were sustained up to week 16 (Table 8). As seen in Table 8 and Figure 9, there is a dose-dependent relationship - 88- WO 2012/059598 PCT/EP2011/069476 54388 FF in DAS28-CRP, ACR20, and ACR50 responses at week 16 based on baseline hsCRP levels for secukinumab 150 Mg and 300 mg dose cohorts in comparison to placebo or secukinumab 2 5 mg and 75 mg groups. The safety profile ofsecukinumab up to week 20 was comparable to placebo. Most AEs were mild or moderate in severity and did not lead to study drug discontinuation. Treatment DAS28IACR CRP >=O CRP >10 :CRP >=20 CRP >=30 N 53 25 11 6 Secukinumab DAS28 -1.08 -1.24 -1.46 -1.03 25mg ACR20,% 34 32 36 17 ACR50,% 15 17 19 17 N 49 27 17 10 Secukinumab DAS28 -1.40 -1.50 -1.22 -1.46 75mg ACR20, % 47 49 47 41 ACR50,% 19 112 1 N 43 : 15 11 Secukinumab DAS28 -138 -2.05 -213 -2.09 150mg ACR20 % 46 60 67 62 ACR5O,% 20 28 31 17 N 41 19 10 6 Secukinumab DAS28 -1.30 -1.51 -2.01 -2.21 300mg ACR20, /6 54 64 81 86 ACR50,% 17 19 39 67 N 50 26 .16 12 Placebo DAS28 -0.83 -0.72 -0.47 -0.67 ACR20 0.36 0.31 0.30 0.43 ACR50 0.05 0.03 0.05 0.07 Table 8 - Dose-response relationship for DAS28-CRP, ACR20, and ACR50 at Week 16 by CRP levels at baseline. DAS28-CRP, ACR20, and ACR5O data are given in median; N; number of patients. "0" = 0 mg/m, "10"- 10 mg/ml, "20"= 20 mg/mI, "30" = 30 mg/mI. The results in-dicate that secukinumab provides a rapid reduction of disease activity with the greatest improvements seen in thosepatients on 150 mg or 300mg who had evidence of high inflammatory burden as evidenced by baseline hsCRP levels. This suggests that secukinumab - 89 - WO 2012/059598 PCT/EP2011/069476 54388 FF offers benefit to RA patients including those with factors rendering them at high risk for progressive disease, Example 4: Modeling and Simulation: Rheuinatoid Arthritis;Induction Regimen Design The relationship between ecukinumtab dose/regiien,.secukinumab plasma.concentration and the ACR20 response was modeled using-a PR/PD approach.describingthelongitudinal data. These models were used to facilitate design of Phase Ill trials for secukinuiab in treating rheumatoid arthritis. Example 4.1 -Methods Modeling of Secukinumab pharmacokinetics For the pharmacokinetic (PK) model (Figure 10), data from various clinical studies (CAIN457A 1101, CAIN457A2101, CAIN457A2102, CAIN457A2103, CAIN457A2104, CAIN457A2206, CAFN457A2208, CAIN457A2209 and CAIN457F2201) were pooled. A population approach with a two-compartmental model was used to describe secukinumab PK. The population parameters were estimated together with their interindividual variances, The parameters were: distribution volumes VI =2.96 L and V2=2.52 L, first-order clearance from the first volume CL=0. 169 L/day, intercompartmental exchange coefficient Q=0.784 L/day, and the absorption rate and absolute bioavailability for a subcutaneous administration were KA= 0.192 1/day and F=76%, respectively. Body weight was identified as a covariate on secukinumab clearance and volumes. Modeling of ACR20 responderrates in placebo and seculdnumab treatment groups. For ACR20 modeling data on methotrexate inadequate responder patients (Table 9), data from two clinical studies (CAIN457A2 101 and CA1N457F2201) were used. ACR20 responder rates were modeled using a concentration-responder probability approach for the placebo and treated groups. The assumption was that the A CR20 response rate increased monotonically until 16 weeks for placebo and treated groups. The monotonically increasing curve depended on the logarithm of time and the square root of secukinumab concentration. The observed ACR20 (LoCF) at weeks, 4 (day 29), 8 (day 57), 12 (day 86) and 16 (day 13) was modeled in two steps for placebo and the treated group. - 90 - WO 2012/059598 PCT/EP2011/069476 54388 FF ACR20 time profile model for placebo group The observed ACR20 at time ti (i1,2,3,4 denotes week 4, 8, 12 and 16) for j-th patient in placebo group was written as: ACR20o(t 1 ) -binomial( lIpo(tr)) Logit(pa(ti))=a+P log(tj)/log(t4). Thus the logit of the ACR20 response rate in the placebo group at week 16 was a + p and at time 0 it was -no which corresponds to a probability to respond of D at time zero. ACRZO time profile model for secukinumab treated group The observed ACR20 at time t for the j-th patients in secukinumab treated group was written as: ACR20j(ti) -binomial(1,p(t)) Logit(p(ti))= Lhit(po(to)(t)h(conc(ti)) 1 wheehO was the square root of the individual model predicted concentration. Here y was the change of sensitivity ofACR2O responder rate to the concentration at time ti. yT) = YO log(ti)/1og9t4) Hence the effect of secukinumab was described by y(ti)h(conc 1 (t)). The functional form y was chosen to be the log of study day, the same as placebo time effects, in other words a proportional odds in h(conc) was assumed. The generalized estimating equation method was used for the evaluation and the within patient correlation of the ACR20 observed response were assumed to be compound symmetry. Example 4.2- Results Example 4.2.1 - PK Modeling Results As can be seen in Figure 10, the model predicts that a higher secukinumab plasma concentration can be achieved using either an i.v. or s.c. induction regimen in comparison to no induction regimen. Furthermore, the model further predicts that an induction regimen that uses 10 mg/kg secukinumab delivered i.v. at weeks 0, 2 and 4 can provide higher plasma concentration of secukinumab (and at a more rapid rate) than an induction regimen that uses 300 mg secukinumab delivered s.c. at weeks 0, 1,2,3 and 4. The s.c and Lv. induction regimens - 91 - WO 2012/059598 PCT/EP2011/069476 54388 FF modeled provided improved response in comparison to a dosing regimen lacking an induction regimen. Example 4.2.4 - ACR20 Simulation Results The results from the ACR20 responder modeling are presented in Table 9. The ACR20 simulation predicts that a greater ACR20: response rate can be achieved using either an iv. (63%) or s.c. (57%) induction regimen in comparison to no induction regimen (35%). Furthermore, the model further predicts that an induction regimen that uses 10 mg/kg secukinumab delivered i.v. at weeks 0, 2 and 4 can provide a greater ACR20 response rate than an induction regimen that uses 300 mg secukinumab delivered s.c. at weeks 0, 1, 2, 3 and 4. The s.c. and Lv. induction regimens modeled provided improved response in comparison to a dosing regimen lacking an induction regimen. Induction strategy Inducton dose -;regime ACR2O:response at week 4 with 95% confidenceinterval No induction 300 mg s.c. every 4 weeks 35% (27-46) inductionn using 300 mg s.c. at Weeks 0, 1, 2, 3 and 4 57% (41 -76) s.c. dosing followed by 300 mg s.c. every 4 weeks Induction using 10 mg/kg i.v. at Weeks 0, 2 and 4 63% (47 -81) i.v. dosing followed by 300 mg s.c. every 4 weeks Table 9 - Simulated ACR20 responder rates. Example 5: Secukinumab shows Good Safety and Efficacy in the Treattent of Active Ankylosing Spondylitis Example 5.1 - Study Design CAIN457A2209 CAfN457A2209 is a pase II, multicenter, randomized, double-blind, parallel-group, placebo controlled proof-of concept study in patients with moderate to severe AS. The study population is patients of age 18-65 years with AS diagnosed. according to the modified New York criteria, back pain & nocturnal pain score : 4 (0-10:point scale), a BASDAI score 4 (0 10 point scale), and inadequate response to current or previous use of at least one NSAID given over at least 3 months at maximum recommended dose. Patients with previous TNF-a blocker - 92 - WO 2012/059598 PCT/EP2011/069476 54388 FF use were allowed to enroll after appropriate wash-out periods. Patients were allowed to continue concurrent treatment with NSAIDS, methotrexate (MTX), sulphasalazine, and prednisolone at stable doses during the study. However, patients with evidence of active tuberculosis were excluded. Thirty (30) patients were randomised in a 4:1 ratio to receive two i.v infusions of either secukinumab (AIN457): 10 mg/kg iv. or placebo Lvi.given 3 weeks apart. Patients will be followed for safety up to week.28. A Bayesian analysis ofthe Week 6 ASAS20response rates of AIN457 and placebo was: performed. The. pdor distributions for the response rates were specified as Beta distributions and the binomial distributionwas assured for the observed number of responders in each group. The predictive distribution of the placebo response rate from a meta analysis of 8 randomized, placebo-controlled trials of anti-TNFalpha treatment in AS was used as the prior distribution for the placebo response rate. This prior was equivalent to observing I I out of 43 responders (i.e. a response rate of 26%). A weak prior was used for the active response rate (equivalent to observing 0.5 out of 1.5 responders). Ther primary end point was the proportion of patients achieving the Assessment of Spondylo Arthritisinternational Society (ASAS) 20 response at week 6. Example 5.2 - Results Demographics and baseline characteristics were comparable between groups. Mean (SD) BASDAI at baseline was 7.1 (1.4) for secukinumab-treated patients and 7.2 (1.8) for placebo treated patients. Three patients on placebo and 2 patients on AIN457 discontinued the study prior to the primary endpoint, mostly due to unsatisfactory therapeutic effect. Efficacy data from I patient was not available due to a protocol violation after randomization. At week 6, 14/23 secukinumab-treated patients who entered efficacy analysis achieved ASAS2( responses versus [/6 placebo treated patients (611% vs 17%,;probability of positive-treatment difference=99.8%, credible interval 11.5%, 56.3%). ASAS40 and ASAS5/6 responses of secukinumab-treated patients were 30% and 35%, respectively, and mean (range) BASDAI change was -1.8 (-5.6 to 0.8). In a majority of the ASAS20 responders, secukinumab induced responses within a week of treatment. The pharmacokinetic profile was as expected for an IgG I mAb and comparable to secukinumab given for other indications. The primary endpoint of this study was met, as secukinumab induced significantly higher ASAS20 responses than placebo at week 6. No early safety signals were noted in this study - 93 - WO 2012/059598 PCTIEP2011/069476 54388 FF population. Interim data presented here suggests, that secukinumab has-use in treating active ankylosing spondylitis. Example 6--Secukinumab Reduces Signs and-Symptoms oflPsoriatic Arthrifis in a 24 Week Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial Example 6.1 - Study Design and Demographics Fourty-two patients with active psoriatic arthritis (PsA) fulfilling CASPAR criteria were assigned 2:1 to receive two injections with secukinumab (10 mg/kg) or placebo, given three weeks apart. The primary efficacy endpoint.was the proportion of ACR20 responders at Week 6 in active compared with placebo recipients (one-sided p-value <0.1). As per protocol, no imputation was made for missing data (drop-outs were treated as missing). Twenty-five (89%) patients on secukinumab and 10 (71%) on placebo completed the study. Five patients (4 secukinumab and I placebo) weretexcluded from the efficacy analysis due to protocol violations. Three (11%) of patients on secukinumab and 4 (29%) on placebo discontinued prematurely for lack of efficacy or withdrawal of consent. Demographics and baseline characteristics were balanced between groups for age, sex and parameters including mean (SD) SJC (secukinumab vs. placebo): 8.3 (5.6) vs. 9.5 (5,4); TJC 23.5:(19.4) vs. 22.6 (I 1.0); DAS2S 4.8 (1.2) vs. 4.8 (12); MASES 3.0 (4.1) vs. 3.4(23). Co-existing psoriasis, prior TNFi exposure and co-medication with DMARDS were presenting 23 (98o), 11(46%) and 21 (88%) patients on secukinumab and in 11 (89%), 5 (38%) and 10 (70%) onplacebo, respectively. Example 6.2 - Results The ACR20 response rate at week 6 was 39% (9/23) on secukinumab vs. 23% (3/13) on placebo (P = 0.27). ACR20 response rates were 39% (9/23) vs. 15% (2/13) at week 12, and 43% (10/23) vs. 18% (2/11) at week 28 with secukinumab versus placebo, respectively. ACR50 and ACR70 response rates at week 6 on secukinumab vs. placebo were 17% vs. 8 % and 9% vs. 0%, respectively. CRP reductions at week 6 compared to baseline were observed on secukinumab (median [range] of 5.0 {0.3, 43.0] at baseline vs. 3.0 [0.2, 15.2] at week 6, but not on placebo (3.9 [1.3, 39.7) at baseline vs. 5.0 [0.8, 29.6] at week 6). Similar reductions were seen for ESR, and reductions in acute phase parameters were maintained up to week 28. The overall rate of adverse events (AEs) was comparable in secukinumab versus placebo: 26 (94%) vs. 11 (79%). One severe adverse event (cellulitis hand) occurred on secukinumab, and was not suspected by -94 - WO 2012/059598 PCT/EP2011/069476 54388 FP the investigator to be study drug-related. Seven serious AEs were reported in 4 secukinumab patients (tendon rupture/carpal tunnel syndrome/oellulitis, obesity, fall, breast cancer [diagnosed prior to dosing and inclusion constituting a protocol violation]) and I with placebo (polyarthritis). Infections were reported in 16 (57%) patients on secukinumab and 7 (50%) patients on placebo. The safety profile of secukinumab was favorable.overal Although the primary endpoint was not met, a substantial proportion of patients showed rapid and sustained improvements of clinical scores and acute phase parameters up to week 28. Trends towards a beneficial clinical effect support the rationale for larger clinical trials designed to assess clinical effectiveness. Example 7 - Pharmokinetic (PK) Information for seckukinumab Based on data obtained from various studies, including those discussed in the above Examples,. the following PK information has been obtained for seckukinumab (Table 10),. Experimental Induction Average C. 401 pg/mi at end of third 10 mg/kg i.v. infusion for a 90 kg human ( 30%-40% inter-patient variation) Maintenance (75, 150 or 300 mg s.c. monthly) Average steady-state trough levels for a 75 kg.human (30% inter-patient variation): 9.4 pg/ml (e.g., 75 mg dose) 17.3 pg/mI (eg., 150 mg dose) 31 pg/ml (e.g., 300 mg dose) A UC tau ranges at steady state: 314 mg*day/L (e.g., 75 mg dose) 628 mg*day/L (e.g., 150 mg dose) 1256 mg*day/L (e.g., 300 mg dose) Simulated Induction Average Cmlx 240 pg/ml after the first dose and 360 pg/ml after the third iv. infusion for a 75 kg human. Trough levels maintained above 80 pg/ml over a 10 week period. Maintenance (75, 150 or 300 rMg s.c. monthly beginning week 8) - 95 - WO 2012/059598 PCT/EP2011/069476 54388 FF Average steady-state trough levels for a 75 kg human: 8.0 pg/ml (e.g., 75 mg dose) 17 pg/ml (e.g., 150 mg dose) 30 pg/ml (e.g., 300 mg dose) AUC tau (mg*day/L) at'steady state (The q025 and q975 give the AUC range having 95% of the patients); dose Auce. AUCA AUC AUC 5 75 331 309 128 657 150 661 618 257 1315 300 1323 1237 513 2629 Table 10: Experimental and simulated pharmokinetic values for secukinumab. In addition, it has been determined that secukinumab has a T. of about 7-8 days, and an elimination half-life of about 30 days. This PK information can. be used to design different dosing regimens for treatment of arthritis, e.g., RA, -e.g., high risk RA. Using this PK information, one can deliver a different dosage of the IL-17 antagonist, esg., an IL-17 binding molecule (e.g., an IL-17 antibody, such as secukinumab) or an IL-17 receptor binding molecule (e.g., an IL- 17 receptor antibody) from the dosages used in the Examples or deliver the same dosage as used in the Examples, but which is provided at a different time point from the time points used in the Examples. By maintaining the same PK profile, even though a dosing regimen or a dosage may change, a skilled artisan is expected to be able to employ an the IL-17 antagonist, e.g, an IL- 17 bindingiofecule (e.g., an IL-17 antibody, such as secukinumab) or an IL-1 7 receptor binding molecule (e.g., an IL-1-7 receptor antibody) for treatment of arthritis, including treatment of high risk RA patients. Example 8: Pharmaceutical Compositions / Medicaments Comprising an IL-17 Antagonist. A formulation study using secukinumab drug substance was initiated with the aim of developing a product of high strength, e.g., a vial having a unity dose of 150 mg secukinumab, Four sucrose-based formulations, in combination with different stabilizers (mannitol, glycine, arginine HCI), were included in the stability program at real, accelerated and stressed conditions for 12 months (Table 11). - 96 - WO 2012/059598 PCT/EP2011/069476 54388 FF Form AIN457 Cone Buffer StabilIzer/Bullting agent Surfactant pH Before yophilization I 50mg/mL -10mM Hlstidine 90mM Sucrose 0.42% Polysorbate 80 58 2 50mg/mL I0mM Histidine 2DMM Sucrose 0.02% POlysorbats 80 5.8 0M Mannitol 3 50mg/mL 10mM Histidine 70mM Sucrose, 0.02% Polysortate 80 5.8 20mM Glycine 4 50mg/mL 10mM Histidine 65mM Sucrose, 0.02% Polysorbate 80 5.8 15mM Arginine After reconstitution of the lyophilisate 1 150mgmL 30mM Histidine 270mM Sucrose 0.06% Polysorbate 80 5.8 2 150mg/mL 30rM Histidine 60mM Sucrose, 0.06% Polysorbate 80 5.8 180mM Mannitol 3 150mg/mL 30mM Histidine 210mM Sucrose, 0:06% Polysorbate 80 5.8 ymM Glycine 4 150mg/mL 30mM Histidine 195mM Sucrose, 0.06% Polysorbate 80 5.8 45mMArginine Table 11 - Formulations included in stablity study All formulations were filled at 3.6 mL (20 % overfill) into 6 mL type I glass vials, capped with a Flurotec@ B2 coated lyo configuration stopper and lyophilized using a conservative lyophilization cycle (Table 12). Step Operation Time[Ihimmj Shslf Temperature Chamber Pressure 1 Vial loading As required .20*C Ambient 2 Cooling down 00:30 *C Ambient 3 5'C hold 03:00 5 1 C Aribient 4 Freeze ramp 01:24 6C to -37 0 C Ambient 5 Freeze hold 06:00 -37*C Ambient 6 Chamber vacuum 00:10 -37'C 0.2 mbar 7 Primary drying ramp 16:00 -37'C to 25vC 0.2 mbar 6 Secondary drying 24:00 25 0 C 0.2 mbar 9 Vial stoppering 25'C 850 ± 50 mbar Table 12 -Lyophilization cycle conditions. Secukinumab stability was monitored in the formulations through determination of cake appearance, pH, reconstitution time, residual moisture by Karl Fischer, aggregates and degradation products by SE-HPLC, impurities by SDS-PAGE under reducing conditions, average molecular weight by LLS, degradation products by RP-HPLC and theoretical activity by -97- WO 2012/059598 PCT/EP2011/069476 54388 FF cystamine CEX. Osmolality and viscosity were determined afier reconstitution 3:1 with waterfor injection at initial timepoint (Table 13). Form Formulation OsmolelIty (flOsm/KgJ Viscosity (mPa's) 1 270mM Sucrose 452 10.8 2 60mM Sucrose, 180mM Mannitol 388 103 3 210mM Sucrose, 60mM Glycine 440 10.5 4 195mM Sucrose, 45mM Arginine 421 9.7 Table 13 - Osmolality and viscosity values for given formulations. Osmolality values were well within the limit of PhEur acceptance criteria of higher than 24OmOsm/Kg and viscosity results in an acceptable range of I OmPa*s. The 12 month stability data from samples stored at real temperature conditions indicated no differences in purity profile among the formulationswith te different stabilizers; Nosigiiicant difference. among formulations was observed in appearance of lyophilisate cake and pH upon storage however, the formulation containing mannitol showed a slightly longer reconstitution time when compared to the others (6 vs. 3 minutes). Moisture content increased from approximately 0.2% to 0.4% irrespective of formulation (data not shown), Aggregates by SEH4PLC increased from approximately 0.9% to 1.4% whereas the degradation products were below the limit of quantification (data not shown). A1N457 average molecular weight remained unchanged after storage at approximately 155kDa, Starting levels of total RP-HPLC species were approximately 8.5-10% with a significant increase up to 14,6% upon 12 months storage at PC (data not shown). It should be highlighted that these levels reached a plateau from 1 month storage onwards. The A N457 activity by Cystamine CEX was kept at 98-99% (data not shown). The 6 months stability data from samples stored at accelerated and stressed temperature conditions revealed that the formulation containing sucrose + mannitol was clearly differentiated from the others in terms of the longest reconstitution time (6 min vs. 3 min), highest aggregation product levels and generation of RP-HPLCdegradation products upon storage. No significant difference among formulations was observed in appearance of lyophilisate cake and pH upon storage. Moisture content increased from approximately 0.2 % to 0.6-0.7 % irrespective of composition after 6 months storage at 40 *C (data not shown). The sucrose containing formulation showed a slightly lower aggregation level than the other formulations containing, additionally, mannitol, glycine - 98 - H:%adnpienroven\NRPnnb\DCC\DARM36N40_I doc.,-29)/i0/20HI and arginine HCI (5.2% vs. 5.8-6.8% by SE-HPLC). For all formulations, degradation products were below the limit of quantification (data not shown). AIN457 average molecular weight remained unchanged after 6 months storage at 40*C at approximately 160kDa. Total RP-HPLC degradation products were at slightly lower levels in the stand alone sucrose based formulation or with arginine HCl of up to 31.0% and 31 .4% when compared to 32.8 and 35.6% in the other two formulations upon 6 months storage at 40*C (data not shown). The AfN457 activity by cystamine CEX was kept at 94 95% (data not shown). Results from the study showed that the 90 mM sucrose based formulation at 50 mg mL in 10 mM histidine, 0.02 % polysorbate 80, pH 5.8 priorto lyophilization was the most suitable candidate for market formulation containing 150 mg/mL A1N457, 30 mM L-histidine buffer pH 5.8, 270 mM sucrose and 0.06 % polysorbate 80 after 3: 1 reconstitution with 1.0 mL of water for injection. Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. - 99 -

Claims (17)

1. Use of an IL- 17 antibody in the manufacture of a medicament for treating ankylosing spondylitis (AS), wherein the IL- 17 antibody binds to an epitope of an IL- 17 homodimer having two mature IL-17 protein chains, said epitope comprising Leu74, Tyr85, His86, Met87, Asn88, Val124, Thr125, Pro126, Ilel27, Val128, His129 on one chain and Tyr43, Tyr44, Arg46, Ala79, Asp80 on the other chain, wherein the IL- 17 antibody has a KD of about 100-200 pM, and wherein the IL- 17 antibody has an in vivo half-life of about 4 weeks; and wherein the medicament is for: a) subcutaneous administration to a patient having AS of five doses of about 150 mg - about 300 mg of the IL-17 antibody, each of the five doses being delivered weekly; and b) thereafter, subcutaneous administration of a dose of about 150 mg -about 300 mg to the patient every month, beginning one month from the fifth subcutaneous dose according to step a).

2. The use according to claim 1, wherein the IL-17 antibody is subcutaneously administered as doses of about 150 mg - about 300 mg during weeks 0, 1, 2, 3, 4, and 8, and then monthly thereafter.

3. The use according to claim 2, wherein the patient has moderate to severe active AS.

4. The use according to claim 2, wherein all doses according to step a) and all doses according to step b) are about 150 mg.

5. The use according to claim 2, wherein the patient previously had an inadequate response to at least one NSAID.

6. The use according to claim 2, wherein the patient is a TNF failure or a DMARD failure. -100 - H:\dar\Ineroen\NRPortb\DCC\AR\6936040_ L.doc.-29/IW2014

7. The use according to claim 2, further comprising administering an NSAID, methotrexate, sulphasalazine, or prednisolone to the patient.

8. The use according to any one of claims 1-7, wherein the IL-17 antibody: i) comprises an immunoglobulin heavy chain variable domain (VH) comprising the amino acid sequence set forth as SEQ ID NO:8; ii) comprises an immunoglobulin light chain variable domain (VL) comprising the amino acid sequence set forth as SEQ ID NO: 10; iii) comprises an immunoglobulin VH domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth as SEQ ID NO: 10; iv) comprises an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3; v) comprises an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; vi) comprises an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO:12 and SEQ ID NO:13; vii) comprises an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariabie regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or viii) comprises an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO:11, SEQ ID NO:12 and SEQ ID NO:13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.

9. Use of an IL-17 antibody in the manufacture of a medicament for treating AS, wherein the IL- 17 antibody comprises: i) an immunoglobulin V 8 domain comprising the amino acid sequence set forth as SEQ ID NO:8 and an immunoglobulin VL domain comprising the amino acid sequence set forth as SEQ ID NO: 10; - 101 - H IdarlicnroverNRPonbl\DCC\AR 36 040 -1 dcx-29/ 10/21114 ii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 1, SEQ ID NO:2, and SEQ ID NO:3 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; or iii) an immunoglobulin VH domain comprising the hypervariable regions set forth as SEQ ID NO: 11, SEQ ID NO: 12 and SEQ ID NO: 13 and an immunoglobulin VL domain comprising the hypervariable regions set forth as SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6; and wherein the medicament is for: a) subcutaneous administration to a patient in need thereof five doses of about 150 mg - about 300 mg of the IL-17 antibody, each of the five doses being delivered weekly; and b) thereafter, subcutaneous administration to a patient a dose of about 150 mg about 300 mg of IL-17 antibody every month.

10. The use according to claim 9, wherein the IL-17 antibody is subcutaneously administered as doses of about 150 mg - about 300 mg during weeks 0, 1, 2, 3, 4, and 8, and then monthly thereafter.

11. The use according to claim 10, wherein the patient has moderate to severe active AS.

12. The use according to claim 10, wherein all doses according to step a) and all doses according to step b) are about 150 mg.

13. The use according to claim 10, wherein the patient previously had an inadequate response to at least one NSAID.

14. The use according to claim 10, wherein the patient is a TNF failure or a DMARD failure, - 102 - H-darintcrwm n\NRPofblDCC\DAR\6936I40Ii 1dex-29/30/2014

15. The use according to claim 10, further comprising administering an NSAID, methotrexate, sulphasalazine, or prednisolone to the patient.

16. The use according to any one of the preceding claims, wherein the IL- 17 antibody is secukinumab.

17. Use of secukinumab in the manufacture of a medicament for treating active AS wherein about 150 mg secukinumab is administered by subcutaneous injection to a patient in need thereof, with initial dosing at weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at week 4. - 103 -