TNF-alpha ANTAGONISTS AND METHOTREXATE IN THE TREATMENT OF TNF-MEDIATED DISEASE

Abstract

Methods for treating and/or preventing a TNF-mediated disease in an individual are disclosed. Also disclosed is a composition comprising methotrexate and an anti-tumor necrosis factor antibody. TNF-mediated diseases include rheumatoid arthritis, Crohn's disease, and acute and chronic immune diseases associated with transplantation.

1 - 38 . (canceled) 
     
     
         39 . A method of suppressing an immune response to a recombinant anti-human tumor necrosis factor-α monoclonal antibody in an individual suffering from rheumatoid arthritis to whom the antibody is administered, which comprises treating the individual according to a regimen comprising administering to the individual multiple doses of the antibody at a dosage between 0.01 and 100 mg/kg of the individual's body weight at intervals of weeks so as to induce immunological tolerance to the antibody and administering multiple doses of methotrexate at an interval of a week or weeks so as to potentiate said immunological tolerance in the individual and thereby suppress the individual's immune response to the antibody. 
     
     
         40 . The method of  claim 39 , wherein the antibody is administered subcutaneously or by intravenous infusion and is a chimeric, human, or humanized monoclonal antibody. 
     
     
         41 . The method of  claim 40 , wherein the antibody is administered by intravenous infusion and is a chimeric monoclonal antibody. 
     
     
         42 . The method of  claim 41 , wherein the chimeric monoclonal antibody is cA2 and is administered as multiple infusions at a dosage between 1 and 20 mg/kg body weight of the individual. 
     
     
         43 . The method of  claim 42 , wherein the chimeric monoclonal antibody cA2 is administered as multiple infusions of 3 mg/kg body weight of the individual. 
     
     
         44 . The method of  claim 42 , wherein the chimeric monoclonal antibody cA2 is administered as multiple infusions of 10 mg/kg body weight of the individual. 
     
     
         45 . The method of  claim 40 , wherein the antibody is administered subcutaneously and is a human or humanized monoclonal antibody. 
     
     
         46 . The method of  claim 39 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         47 . The method of  claim 40 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         48 . The method of  claim 41 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         49 . The method of  claim 42 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         50 . The method of  claim 43 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         51 . The method of  claim 44 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         52 . The method of  claim 45 , wherein the antibody is administered adjunctively with the administration of methotrexate. 
     
     
         53 . The method of  claim 39 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         54 . The method of  claim 40 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         55 . The method of  claim 41 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         56 . The method of  claim 42 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         57 . The method of  claim 43 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         58 . The method of  claim 44 , wherein the antibody is administered concomitantly with the administration of methotrexate. 
     
     
         59 . The method of  claim 45 , wherein the antibody is administered concomitantly with the administration of methotrexate.