Methods of treating ankylosing spondylitis using il-17 antagonists

Abstract

The disclosure relates to novel regimens for treating an inflammatory arthiritis, e.g., psoriatic arthritis, which employ a therapeutically effective amount of an Interleukin-17 (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).

1 . A method of treating inflammatory arthritis in a patient in need thereof using an IL-17 antagonist, wherein the method comprises administering about 75 mg to about 350 mg of the IL-17 antagonist subcutaneously to the patient,
 wherein the IL-17 antagonist is a monoclonal, neutralizing IL-17 antibody that binds to IL-17A.   
     
     
         2 . The method according to  claim 1 , wherein inflammatory arthritis is spondyloarthropathy, ankylosing spondylitis or psoriatic arthritis. 
     
     
         3 . The method according to  claim 1 , wherein the IL-17 antagonist is administered at a dose of about 75 mg to about 350 mg every 4 weeks to the patient. 
     
     
         4 . The method according to  claim 1 , wherein the administration comprises:
 a) administering an initial dose of about 75 mg to about 350 mg of the IL-17 antagonist subcutaneously to the patient every two weeks or every four weeks; and   b) thereafter administering a maintenance dose of about 75 mg to about 350 mg of the IL-17 antagonist subcutaneously to the patient during a maintenance regimen.   
     
     
         5 . The method according to  claim 4 , wherein the maintenance regimen comprises (i) a continuous monthly treatment, or (ii) an intermittent dosing at start of relapse. 
     
     
         6 . The method according to  claim 4 , wherein the maintenance regimen comprises treating the patient with a maintenance dose every month, every two months, or every three months. 
     
     
         7 . The method according to  claim 1 , wherein the patient is an adult. 
     
     
         8 . The method according to  claim 1 , wherein the IL-17 antibody is an IgG 1  isotype. 
     
     
         9 . The method according to  claim 1 , wherein the IL-17 antibody is fully human or humanized. 
     
     
         10 . The method according to  claim 1 , wherein the IL-17 antibody binds to an epitope of IL-17 comprising any one of Tyr 44, Arg46, His86, Val128, His129, or a combination thereof. 
     
     
         11 . The method according to  claim 1 , wherein the IL-17 antibody binds to an epitope of IL-17 comprising Tyr 44, Arg46. 
     
     
         12 . The method according to  claim 4 , wherein the initial dose comprises about 320 mg of the IL-17 antibody. 
     
     
         13 . The method according to  claim 4 , wherein the maintenance dose comprises about 160 mg of the IL-17 antibody. 
     
     
         14 . The method according to  claim 4 , wherein the maintenance regimen comprises subcutaneously administering to the patient a maintenance dose of about 150 mg to about 175 mg of the IL-17 antibody twice a month, monthly, every two months or every three months. 
     
     
         15 . The method according to  claim 14 , wherein the maintenance regimen comprises subcutaneously administering to the patient a maintenance dose of about 150 mg to about 175 mg of the IL-17 antibody monthly. 
     
     
         16 . The method according to  claim 15 , wherein the maintenance regimen comprises treating the patient with a maintenance dose of about 160 mg of the IL-17 antibody monthly. 
     
     
         17 . The method according to  claim 1 , wherein the inflammatory arthritis is indicated by a level of C-reactive protein (CRP)≥10 mg/L, as measured by hsCRP. 
     
     
         18 . The method according to  claim 4 , wherein the initial dose is subcutaneously administered to the patient at about 250 mg to about 350 mg of the IL-17 antibody twice a month, monthly, every two months or every three months. 
     
     
         19 . The method according to  claim 18 , wherein the initial dose is subcutaneously administered to the patient at about 320 mg of the IL-17 antibody monthly. 
     
     
         20 . The method according to  claim 1 , wherein the IL-17 antagonist comprises an IC 50  for inhibition of IL-6 production, in the presence of 1 nM human IL-17, of about 50 nM or less, as measured on IL-6 production induced by human IL-17 in human dermal fibroblasts. 
     
     
         21 . The method according to  claim 1 , wherein the IL-17 antibody comprises an in vivo half-life of from about 23 days to about 30 days. 
     
     
         22 . The method according to  claim 1 , wherein the IL-17 antibody comprises a T max  of about 7-8 days.