Use of human TNFα antibodies for treatment of erosive polyarthritis

1. A method for inhibiting radiographic disease progression in a human subject having erosive polyarthritis associated with a disorder in which TNFα activity is detrimental, comprising administering to the subject having erosive polyarthritis an isolated human anti-TNFα antibody, or antigen-binding portion thereof, such that radiographic disease progression is inhibited in the subject, wherein a Total Sharp Score (TSS) of the subject is either maintained or decreased following administration of the human anti-TNFα antibody, or antigen-binding portion thereof, wherein the human anti-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.

2. The method of claim 1 , wherein the human anti-TNFα antibody is golimumab, or an antigen-binding portion thereof.

3. The method of claim 1 , wherein the human anti-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.

4. The method of claim 1 , wherein the human anti-TNFα antibody is adalimumab, or an antigen-binding portion thereof.

5. The method of claim 1 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject on a biweekly dosing regimen.

6. The method of claim 1 , further comprising administering an additional therapeutic agent to the subject.

7. The method of claim 6 , wherein the additional therapeutic agent is methotrexate.

8. A method for treating erosive polyarthritis comprising administering to a subject having erosive polyarthritis associated with a disorder in which TNFα activity is detrimental, an amount of a isolated human anti-TNFα antibody, or an antigen-binding portion thereof, such that erosive polyarthritis is treated, wherein the amount of the human TNFα antibody, or antigen-binding portion thereof, results in a statistically significant reduction or inhibition in joint damage as measured by a Total Sharp Score (TSS), wherein the human anti-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.

9. The method of claim 8 , wherein the disorder in which TNFα is detrimental is an autoimmune disease or a spondyloarthropathy.

10. The method of claim 9 , wherein the autoimmune disorder is rheumatoid arthritis or juvenile rheumatoid arthritis.

11. The method of claim 9 , wherein the spondyloarthropathy is ankylosing spondylitis or psoriatic arthritis.

12. The method of claim 8 , further comprising administering an additional therapeutic agent to the subject.

13. The method of claim 8 , wherein the additional therapeutic agent is methotrexate.

14. A method for inhibiting radiographic progression of joint disease associated with erosive polyarthritis in a subject having erosive polyarthritis associated with psoriatic arthritis or rheumatoid arthritis, said method comprising administering to the subject having erosive polyarthritis, adalimumab on a biweekly dosing regimen, such that radiographic progression is inhibited, wherein a Total Sharp Score (TSS) of the subject is maintained or decreased following administration of adalimumab.

15. The method of claim 1 , wherein the disorder in which TNFα is detrimental is an autoimmune disease or a spondyloarthropathy.

16. The method of claim 15 , wherein the autoimmune disease is rheumatoid arthritis, or juvenile rheumatoid arthritis.

17. The method of claim 15 , wherein the spondyloarthropathy is ankylosing spondylitis or psoriatic arthritis.

18. The method of claim 8 , wherein the human anti-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.

19. The method of claim 8 , wherein the human anti-TNFα antibody is adalimumab, or an antigen-binding portion thereof.

20. The method of claim 8 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject on a biweekly dosing regimen.

21. The method of claim 8 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, is administered at a dose of about 40 mg.

22. A method for treating erosive polyarthritis associated with a disorder in which TNFα activity is detrimental, said method comprising identifying a subject having erosive polyarthritis associated with a disorder in which TNFα activity is detrimental and administering to the subject an amount of an isolated human anti-TNFα antibody, or an antigen-binding portion thereof, such that erosive polyarthritis is treated, wherein the human anti-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.

23. The method of claim 22 , wherein the human anti-TNFα antibody is golimumab, or an antigen-binding portion thereof.

24. The method of claim 22 , wherein the human anti-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.

25. The method of claim 22 , wherein the human anti-TNFα antibody is adalimumab, or an antigen-binding portion thereof.

26. The method of claim 22 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, is administered to the subject on a biweekly dosing regimen.

27. The method of claim 22 , wherein the disorder is rheumatoid arthritis, or juvenile rheumatoid arthritis.

28. The method of claim 22 , further comprising administering an additional therapeutic agent to the subject.

29. The method of claim 28 , wherein the additional therapeutic agent is methotrexate.

30. The method of claim 1 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, comprises:

a light chain variable region (LCVR) comprising a CDR3 domain set forth in 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, and/or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 7;

and a heavy chain variable region (HCVR) comprising a CDR3 domain set forth in 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, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 8.

31. The method of claim 8 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, comprises:

a light chain variable region (LCVR) comprising a CDR3 domain set forth in 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, and/or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 7; and

a heavy chain variable region (HCVR) comprising a CDR3 domain set forth in 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, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 8.

32. The method of claim 14 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, comprises:

a light chain variable region (LCVR) comprising a CDR3 domain set forth in 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, and/or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 7; and

a heavy chain variable region (HCVR) comprising a CDR3 domain set forth in 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, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 8.

33. The method of claim 22 , wherein the human anti-TNFα antibody, or antigen-binding portion thereof, comprises:

a light chain variable region (LCVR) comprising a CDR3 domain set forth in 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, and/or 8 or by one to five conservative amino acid substitutions at positions 1, 3, 4, 6, 7, 8 and/or 9, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 5, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 7; and

a heavy chain variable region (HCVR) comprising a CDR3 domain set forth in 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, a CDR2 domain set forth in the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain set forth in the amino acid sequence of SEQ ID NO: 8.