Methods of treating psoriasis using il-17 antagonists

Abstract

The disclosure relates to novel regimens for treating psoriasis, which employ a therapeutically effective amount of an IL-17 antagonist, e.g., an IL-17 binding molecule, e.g., an IL-17 antibody, such as the secukinumab antibody, or an IL-17 receptor binding molecule, e.g., an IL-17 receptor binding molecule, e.g., an IL-17 receptor antibody.

1 . A method of treating psoriasis in a patient in need thereof using an IL-17 antagonist,
 wherein the method comprises:
 a) administering a loading dose greater than about 75 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, 
   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 the maintenance regimen comprises (i) a continuous monthly treatment, or (ii) an intermittent dosing at start of relapse. 
     
     
         3 . The method according to  claim 1 , wherein the maintenance regimen comprises treating the patient with a maintenance dose every month, every two months, or every three months. 
     
     
         4 . The method according to  claim 1 , wherein psoriasis is moderate to severe plaque-type psoriasis. 
     
     
         5 . The method according to  claim 1 , wherein the patient is an adult. 
     
     
         6 . The method according to  claim 1 , wherein the patient is a candidate for systemic therapy. 
     
     
         7 . The method according to  claim 1 , wherein the IL-17 antibody is an IgG 1  isotype. 
     
     
         8 . The method according to  claim 1 , wherein the IL-17 antibody is fully human or humanized. 
     
     
         9 . 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, Va1128, His129, or a combination thereof. 
     
     
         10 . The method according to  claim 1 , wherein the IL-17 antibody binds to an epitope of IL-17 comprising Tyr 44, Arg46. 
     
     
         11 . The method according to  claim 1 , wherein the patient is treated with a loading dose of about 75 mg to about 350 mg of the IL-17 antibody. 
     
     
         12 . The method according to  claim 11 , wherein the patient is treated with a loading dose of about 300 mg of the IL-17 antibody. 
     
     
         13 . The method according to  claim 1 , wherein the maintenance regimen comprises treating the patient with a maintenance dose of about 150 mg of the IL-17 antibody. 
     
     
         14 . The method of  claim 3 , wherein the maintenance regimen comprises treating the patient with a maintenance dose monthly. 
     
     
         15 . The method according to  claim 1 , wherein the maintenance regimen provides an average steady-state trough level of the IL-17 antibody of (i) about 11 μg/ml to about 70 μg/ml; or (ii) about 5 μg/ml to about 33 μg/ml. 
     
     
         16 . 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. 
     
     
         17 . 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. 
     
     
         18 . The method according to  claim 1 , wherein the IL-17 antibody comprises a T max  of about 7-8 days.