TNFalpha 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 treating rheumatoid arthritis in a human comprising administering to the human an effective tumor necrosis factor-α inhibiting amount of antibody cA2. 
     
     
         40 . A method of treating rheumatoid arthritis in a human comprising administering to the human an effective tumor necrosis factor-α inhibiting amount of a tumor necrosis factor-α antibody, or antigen binding fragment thereof, wherein the antibody binds to human tumor necrosis factor-α. 
     
     
         41 . The method of  claim 40 , wherein the antibody is cA2. 
     
     
         42 . A method of treating rheumatoid arthritis in a human comprising administering to the human an effective TNFα-inhibiting amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human constant region, wherein said antibody or antigen-binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human tumor necrosis factor TNFα, and (ii) binds to human TNFα with an affinity of at least 1×10 8  liter/mole, measured as an association constant. 
     
     
         43 . A method of treating rheumatoid arthritis in a human comprising administering to the human an effective TNFα-inhibiting amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human IgG1 constant region, wherein said antibody or antigen-binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA-7045) to human TNFα, and (ii) binds to human TNFα with an affinity of at least 1×10 8  liter/mole, measured as an association constant (Ka). 
     
     
         44 . A method of treating rheumatoid arthritis in a human comprising administering to the human an effective TNFα-inhibiting amount of an anti-TNFα antibody or antigen-binding fragment thereof, said antibody comprising a human constant region, wherein said antibody or antigen-binding fragment (i) comprises the antigen-binding regions of A2 (ATCC Accession No. PTA-7045) and (ii) binds to human TNFα with an affinity of at least 1×10 8  liter/mole, measured as an association constant (Ka). 
     
     
         45 . A method of treating rheumatoid arthritis in a human comprising administering to the human an effective TNFα-inhibiting amount of an anti-TNFα antibody or antigen-binding fragment thereof; said antibody comprising a human IgG1 constant region, wherein said antibody or antigen-binding fragment (i) comprises the antigen-binding regions of A2 (ATCC Accession No. PTA-7045), and (ii) binds to human TNFα with an affinity of at least 1×10 8  liter/mole, measured as an association constant (Ka).