In rheumatoid arthritis, changes in autoantibody levels reflect intensity of immunosuppression, not subsequent treatment response

Arthritis Res Ther. 2019 Jan 18;21(1):28. doi: 10.1186/s13075-019-1815-0.


Background: Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies like rheumatoid factor (RF), anti-cyclic citrullinated peptide-2 (anti-CCP2), and anti-carbamylated protein (anti-CarP) antibodies. It is currently unclear whether changes in autoantibody levels are associated with disease activity/treatment outcomes and whether they are modified by treatment intensity. Therefore, we determined longitudinal changes in RA-autoantibody levels, the association between these changes and activity score (DAS) and treatment outcomes, and the effect of intensity of immunosuppressive treatment on levels.

Methods: In 381 seropositive RA patients from the IMPROVED study, we measured IgG, IgM, and IgA of anti-CCP2 and anti-CarP; IgM and IgA of RF; and IgG against four citrullinated and two acetylated peptides at 4-month intervals over the first year of treatment. Following initial prednisone and methotrexate (MTX), treatment was changed every 4 months aiming for DAS < 1.6. We investigated changes in autoantibody levels following treatment escalation versus tapering, and the association of levels with DAS over time, EULAR response, and drug-free remission (DFR) ≥ 1 year.

Results: For all 14 autoantibodies, levels decreased from 0 to 4 months and then rose until 12 months. Following treatment escalation, autoantibody levels dropped markedly, while they rose following tapering: RF IgM levels, a representative autoantibody, dropped 10% after restarting prednisone and rose 15% aU/mL after tapering MTX (p < 0.0001). There was no association between autoantibody levels and DAS over time or EULAR response. Greater relative changes between 0 and 12 months did not predict DFR (0-12-month relative change RF IgM, - 39% for no DFR (n = 126) and - 16% for DFR (n = 18)).

Conclusions: Changes in RA-autoantibody levels are not associated with DAS or long-term treatment response, but reflect intensity of immunosuppression. This suggests that autoantibody levels are modifiable by current therapies, but that modifying levels is in itself of limited clinical relevance.

Trial registration: ISRCTN11916566 . Registered on 7 November 2006.

Keywords: Ant-CCP2; Anti-carbamylated protein antibodies; Autoantibodies; Disease activity; Immunosuppression; Rheumatoid arthritis; Rheumatoid factor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies / immunology*
  • Female
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / immunology*
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prednisone / therapeutic use
  • Severity of Illness Index*


  • Anti-Inflammatory Agents
  • Antirheumatic Agents
  • Autoantibodies
  • Prednisone
  • Methotrexate