Method for treating rheumatoid arthritis with a human il-6 receptor antibody and methotrexate

Abstract

A pharmaceutical composition for the treatment of interleukin-6 (IL-6) related diseases, comprising an interleukin-6 antagonist (IL-6 antagonist) and immunosuppressants. The IL-6 antagonist is preferably an antibody to an interleukin-6 receptor (IL-6R).

1 . A method for treating an interleukin-6 (IL-6) related disease in a patient in need thereof, comprising administering to the patient a combination of (i) 8 mg/kg of humanized anti-interleukin-6 receptor (anti-IL-6R) antibody PM-1 (hPM-1) every four weeks, wherein the anti-IL-6R antibody hPM-1 is administered intravenously, and (ii) methotrexate (MTX) orally administered once per week at a dose in a range of 10 to 25 mg. 
     
     
         2 . The method of  claim 1 , wherein the IL-6 related disease is rheumatoid arthritis. 
     
     
         3 . The method of  claim 1 , wherein the patient prior to treatment had an inadequate response or disease flare on MTX treatment alone. 
     
     
         4 . The method of  claim 1 , wherein the patient has no anti-hPM-1 antibodies following administering the combination of the anti-IL-6R antibody hPM-1 and MTX. 
     
     
         5 . The method of  claim 1 , wherein the patient does not experience hypersensitivity following administering the combination of the anti-IL-6R antibody hPM-1 and MTX. 
     
     
         6 . The method of  claim 1 , wherein the anti-IL-6R antibody hPM-1 is administered four times at four week intervals. 
     
     
         7 . A method for treating rheumatoid arthritis in a patient in need thereof, comprising administering to the patient a combination of (i) 8 mg/kg of humanized anti-interleukin-6 receptor (anti-IL-6R) antibody PM-1 (hPM-1) every four weeks, wherein the anti-IL-6R antibody hPM-1 is administered intravenously, and (ii) methotrexate (MTX) orally administered once per week at a dose in a range of 10 to 25 mg. 
     
     
         8 . The method of  claim 7 , wherein the patient prior to treatment had an inadequate response or disease flare on MTX treatment alone. 
     
     
         9 . The method of  claim 7 , wherein the patient has no anti-hPM-1 antibodies following administering the combination of the anti-IL-6R antibody hPM-1 and MTX. 
     
     
         10 . The method of  claim 7 , wherein the patient does not experience hypersensitivity following administering the combination of the anti-IL-6R antibody hPM-1 and MTX. 
     
     
         11 . The method of  claim 7 , wherein the anti-IL-6R antibody hPM-1 is administered four times at four week intervals. 
     
     
         12 . A method for increasing the likelihood of achieving an American College of Rheumatology (ACR) 70 response in a rheumatoid arthritis patient compared to treating the patient with an immunosuppressant agent alone, comprising administering to the patient a combination of (i) 8 mg/kg of humanized anti-interleukin-6 receptor (anti-IL-6R) antibody PM-1 (hPM-1) every four weeks, wherein the anti-IL-6R antibody hPM-1 is administered intravenously, and (ii) the immunosuppressive agent orally administered in an amount to achieve the ACR70 with the combination. 
     
     
         13 . The method of  claim 12 , wherein the immunosuppressive agent is methotrexate or an anti-rheumatic agent. 
     
     
         14 . The method of  claim 12 , wherein the immunosuppressive agent is methotrexate, azathioprine, hydroxychloroquine, sulfasalazine, leflunomide, or oral gold compound. 
     
     
         15 . The method of  claim 12 , wherein the immunosuppressive agent is methotrexate. 
     
     
         16 . The method of  claim 12 , wherein the immunosuppressive agent is azathioprine. 
     
     
         17 . The method of  claim 12 , wherein the immunosuppressive agent is hydroxychloroquine. 
     
     
         18 . The method of  claim 12 , wherein the immunosuppressive agent is sulfasalazine. 
     
     
         19 . The method of  claim 12 , wherein the immunosuppressive agent is leflunomide. 
     
     
         20 . The method of  claim 15 , wherein the immunosuppressive agent is oral gold compound. 
     
     
         21 . A method for treating a rheumatoid arthritis patient comprising administering to the patient a combination of (i) 8 mg/kg of humanized anti-interleukin-6 receptor (anti-IL-6R) antibody PM-1 (hPM-1) every four weeks, wherein the anti-IL-6R antibody hPM-1 is administered intravenously, and (ii) the immunosuppressive agent orally administered in an amount to treat the rheumatoid arthritis, wherein the immunosuppressive agent is methotrexate, azathioprine, hydroxychloroquine, sulfasalazine, leflunomide, or oral gold compound.