Use of tnf alpha inhibitor

Abstract

The invention describes methods of treating erosive polyarthritis comprising administering a TNFα antibody, or antigen-binding portion thereof. The invention also describes a method for testing the efficacy of a TNFα antibody, or antigen-binding portion thereof, for the treatment of erosive polyarthritis.

1 - 15 . (canceled) 
     
     
         16 . A method for testing the efficacy of a TNFα antibody, or antigen-binding portion thereof, for decreasing radiographic progression of joint disease associated with erosive polyarthritis comprising determining the efficacy of the TNFα antibody, or antigen-binding portion thereof, using a modified Total Sharp Score (mTSS) of a patient population having joint disease associated with erosive polyarthritis and a mTSS of the patient population following administration of the TNFα antibody, or antigen-binding portion thereof, wherein no change or a decrease in the mTSS indicates that the TNFα antibody, or antigen-binding portion thereof, is efficacious for decreasing radiographic progression of joint disease associated with erosive polyarthritis. 
     
     
         17 . The method of  claim 16 , wherein the patient population further has a disorder in which TNFα is detrimental. 
     
     
         18 . The method of  claim 17 , wherein the disorder in which TNFα activity is detrimental is selected from the group consisting of psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. 
     
     
         19 . The method of  claim 16 , wherein the decrease in the mTSS is about −0.2. 
     
     
         20 . The method of  claim 16 , wherein the TNFα antibody, or antigen-binding portion thereof, is an antibody selected from the group consisting of a humanized antibody, a chimeric antibody, a multivalent antibody, and a human antibody. 
     
     
         21 . The method of  claim 16 , wherein the TNFα antibody, or antigen-binding portion thereof, is selected from the group consisting of infliximab, golimumab, and adalimumab. 
     
     
         22 . The method of  claim 20 , wherein the human antibody, or an antigen-binding portion thereof, dissociates from human TNFα with a K d  of 1×10 −8  M or less and a K off  rate constant of 1×10 −3  s −1  or less, both determined by surface plasmon resonance, and neutralizes human TNFα cytotoxicity in a standard in vitro L929 assay with an IC 50  of 1×10 −7  M or less. 
     
     
         23 . The method of  claim 20 , wherein the human antibody, or an antigen-binding portion thereof, has the following characteristics:
 a) dissociates from human TNFα with a K off  rate constant of 1×10 −3  s −1  or less, as determined by surface plasmon resonance;   b) has a light chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 3, or modified from SEQ ID NO: 3 by a single alanine substitution at position 1, 4, 5, 7 or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9;   c) has a heavy chain CDR3 domain comprising the amino acid sequence of SEQ ID NO: 4, or modified from SEQ ID NO: 4 by a single alanine substitution at position 2, 3, 4, 5, 6, 8, 9, 10 or 11 or by one to five conservative amino acid substitutions at positions 2, 3, 4, 5, 6, 8, 9, 10, 11 and/or 12.   
     
     
         24 . The method of  claim 20 , wherein the human antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 1 and a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 2. 
     
     
         25 - 27 . (canceled) 
     
     
         28 . A method for monitoring the effectiveness of a TNFα antibody, or antigen-binding portion thereof, for the treatment of erosive polyarthritis in a human subject comprising determining the effectiveness of the TNFα antibody, or antigen-binding portion thereof, using a baseline modified Total Sharp Score (mTSS) of a patient population having erosive polyarthritis and a mTSS score of a patient population following administration of the TNFα antibody, or antigen-binding portion thereof, wherein a result selected from the group consisting of
 i) a decrease in the mTSS in about 9-27% of the patient population; 
 ii) no change in the mTSS in about 65-73% of the patient population; and 
 iii) an increase in the mTSS in about 9-28% of the patient population indicates that the TNFα antibody, or antigen-binding portion thereof, is effective at treating erosive polyarthritis. 
 
     
     
         29 . The method of  claim 28 , wherein the TNFα antibody, or antigen-binding portion thereof, is an antibody selected from the group consisting of a humanized antibody, a chimeric antibody, a multivalent antibody, and a human antibody. 
     
     
         30 . The method of  claim 28 , wherein the TNFα antibody, or antigen-binding portion thereof, is selected from the group consisting of infliximab, golimumab, and adalimumab. 
     
     
         31 . The method of  claim 29 , wherein the human antibody, or an antigen-binding portion thereof, dissociates from human TNFα with a K d  of 1×10 −8  M or less and a K off  rate constant of 1×10 −3  s −1  or less, both determined by surface plasmon resonance, and neutralizes human TNFα cytotoxicity in a standard in vitro L929 assay with an IC 50  of 1×10 −7  M or less. 
     
     
         32 - 39 . (canceled) 
     
     
         40 . A kit comprising
 a pharmaceutical composition comprising a TNFα antibody, or an antigen-binding portion thereof, and a pharmaceutically acceptable carrier, and   instructions for administration of the pharmaceutical composition for the treatment of erosive polyarthritis.   
     
     
         41 - 48 . (canceled)