Uses and compositions for treatment of rheumatoid arthritis

Abstract

The invention provides methods, uses and compositions for the treatment of rheumatoid arthritis. The invention describes methods and uses for treating rheumatoid arthritis wherein a TNFα inhibitor, such as a human TNFα antibody, or antigen-binding portion thereof. Also described are methods for determining the efficacy of a TNFα inhibitor for treatment of rheumatoid arthritis in a subject.

What is claimed: 
     
         1 . A method of preventing Pneumococcal disease and treating rheumatoid arthritis (RA) in a subject comprising administering a pneumococcal vaccine and a human TNFα antibody, or antigen-binding portion thereof, to the subject, such that Pneumococcal disease is prevented and rheumatoid arthritis is treated. 
     
     
         2 . A method of treating late-onset RA comprising administering a human TNFα antibody, or antigen-binding portion thereof, to a patient having late-onset RA. 
     
     
         3 . The method of  claim 2 , wherein the subject is over 60 years old. 
     
     
         4 . The method of  claim 1 , wherein the human TNFα antibody, or antigen-binding portion thereof, is administered to the subject in a biweekly dosing regimen. 
     
     
         5 . The method of  claim 1 , wherein the human TNFα antibody, or antigen-binding portion thereof, is administered to the subject in a dose of 40 mg. 
     
     
         6 . The method of  claim 1 , wherein the human TNFα antibody, or antigen-binding portion thereof, is administered to the subject subcutaneously. 
     
     
         7 . A method of determining the efficacy of a TNFα inhibitor for treating RA in a subject comprising
 determining an ACR20 response of a patient population having RA and who was administered the TNFα inhibitor, 
 wherein an ACR20 response in at least about 80% of the patient population indicates that the TNFα inhibitor is an effective TNFα inhibitor for the treatment of RA in a subject. 
 
     
     
         8 . The method of  claim 7 , an ACR20 response in at least about 85% of the patient population indicates that the TNFα inhibitor is an effective TNFα inhibitor for the treatment of RA in a subject. 
     
     
         9 . The method of  claim 1 , wherein the human TNFα 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. 
     
     
         10 . The method of  claim 1 , wherein the human TNFα 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. 
 
     
     
         11 . The method of  claim 1 , wherein the human TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) having a 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, and comprises a heavy chain variable region (HCVR) having a 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. 
     
     
         12 . The method of  claim 1 , wherein the human TNFα 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. 
     
     
         13 . The method of  claim 1 , wherein the human TNFα antibody, or an antigen-binding portion thereof, is adalimuinab. 
     
     
         14 . The method of  claim 3 , wherein the human TNFα 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. 
     
     
         15 . The method of  claim 3 , wherein the human TNFα 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. 
 
     
     
         16 . The method of  claim 3 , wherein the human TNFα antibody, or an antigen-binding portion thereof, comprises a light chain variable region (LCVR) having a 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, and comprises a heavy chain variable region (HCVR) having a 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. 
     
     
         17 . The method of  claim 3 , wherein the human TNFα 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. 
     
     
         18 . The method of  claim 3 , wherein the human TNFα antibody, or an antigen-binding portion thereof, is adalimuinab.