Compositions for the treatment of rheumatoid arthritis and methods of using same

Abstract

The present invention provides compositions and methods of treating and improving the symptoms of rheumatoid arthritis using an antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R).

1 . A method of treating rheumatoid arthritis in a subject previously treated by administering methotrexate, and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of an antibody once every two weeks, wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), 
 wherein the VH comprises the three complementarity determining regions (CDRs) found within the sequence of SEQ ID NO:2, wherein the VL comprises the three CDRs found within the sequence of SEQ ID NO:3, and the antibody is administered subcutaneously. 
 
     
     
         2 . The method of  claim 1 , wherein the subject was previously ineffectively treated for rheumatoid arthritis by administering methotrexate. 
     
     
         3 . (canceled) 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the antibody and methotrexate are administered together. 
     
     
         6 . The method of  claim 5 , comprising administering between 6 and 25 mg of methotrexate per week. 
     
     
         7 . (canceled) 
     
     
         8 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The method of  claim 1 , wherein the antibody is administered at about 150 mg per two weeks. 
     
     
         11 . The method of  claim 1 , wherein the antibody is administered at about 200 mg per two weeks. 
     
     
         12 . The method of  claim 1 , wherein the subject achieves at least a 20% improvement in the American College of Rheumatology core set disease index (ACR20) after 12 weeks of treatment. 
     
     
         13 . The method of  claim 1 , wherein the subject achieves at least a 50% improvement in the American College of Rheumatology core set disease index (ACR50) after 12 weeks of treatment. 
     
     
         14 . The method of  claim 1 , wherein the subject achieves at least a 70% improvement in the American College of Rheumatology core set disease index (ACR70) after 12 weeks of treatment. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , wherein the subject has been treated with an anti-TNF-α antagonist for at least 3 months in the last 2 years or the subject was intolerant to at least one TNF-α antagonist. 
     
     
         17 . The method of  claim 16 , wherein the TNF-α antagonist is a biologic anti-TNF-α. 
     
     
         18 . The method of  claim 17 , wherein the TNF-α antagonist is selected from the group consisting of etanercept, infliximab, adalimumab, golimumab and/or certolizumab pegol. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A method of treating rheumatoid arthritis in a subject previously ineffectively treated by administering methotrexate and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of an antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO:2 and a light chain variable region comprising the sequence SEQ ID NO:3 and the antibody is administered subcutaneously, wherein the subject achieves at least a 0.3 improvement in the Health Assessment Questionnaire Disability Index (HAQ-DI) after treatment. 
 
     
     
         22 . A method of treating rheumatoid arthritis in a subject previously ineffectively treated by administering methotrexate and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject:
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of an antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO:2 and a light chain variable region comprising the sequence SEQ ID NO:3, and the antibody is administered subcutaneously, wherein the subject achieves at least a 30 decrease in Visual Acuity Score (VAS) after treatment as compared to baseline. 
 
     
     
         23 . A method of treating rheumatoid arthritis in a subject previously ineffectively treated by administering methotrexate and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject:
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of an antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO:2 and a light chain variable region comprising the sequence SEQ ID NO:3, and the antibody is administered subcutaneously, wherein the subject achieves at least a 1 mg/dL decrease in level of C-reactive protein (CRP) in blood sample and/or urine sample after treatment. 
 
     
     
         24 . A method of treating rheumatoid arthritis in a subject previously ineffectively treated by administering methotrexate and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject:
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO:2 and a light chain variable region comprising the sequence SEQ ID NO:3, and the antibody is administered subcutaneously, wherein the subject achieves an improvement in EULAR (European League Against Rheumatism) index after treatment. 
 
     
     
         25 . A method of treating rheumatoid arthritis in a subject previously ineffectively treated by administering methotrexate and previously ineffectively treated by administering a TNF-α antagonist, the method comprising administering to the subject:
 (a) a therapeutically effective amount of methotrexate, and 
 (b) about 150 mg to about 200 mg of antibody once every two weeks, wherein the antibody comprises a heavy chain variable region comprising the sequence SEQ ID NO:2 and a light chain variable region comprising the sequence SEQ ID NO:3, and the antibody is administered subcutaneously, wherein the subject achieves at least a 0.6 increase in disease activity score (DAS28) after treatment. 
 
     
     
         26 . The method of  claim 21 , wherein the subject achieves the improvement after 12 weeks of treatment. 
     
     
         27 . The method of  claim 21 , wherein the subject was treated with the TNF-α antagonist for at least 3 months in the last 2 years. 
     
     
         28 . The method of  claim 21 , wherein the TNF-α antagonist is a biologic TNF-α antagonist. 
     
     
         29 . The method of  claim 21 , wherein the TNF-α antagonist is selected from the group consisting of etanercept, infliximab, adalimumab, golimumab and certolizumab pegol. 
     
     
         30 . The method of  claim 21 , wherein the antibody is sarilumab. 
     
     
         31 . The method of  claim 21 , comprising administering between 6 and 25 mg of methotrexate per week.