Does Seropositivity Change With RA Therapy?

A subanalysis of the early rheumatoid arthritis (RA) IMPROVED study has shown that changes in RA-autoantibody levels are not associated with disease activity or long-term drug response, but instead reflect the intensity of immunosuppression. Therefore, while autoantibody levels may be modifiable by our best therapies, modifying cyclic citrullinated peptide or rheumatoid factor levels may have limited clinical relevance.

Investigators studied whether changes in rheumatoid factor, anti-cyclic citrullinated peptide-2, or anti-carbamylated protein autoantibody levels would be associated with disease activity or treatment outcomes and whether they are modified by treatment intensity.

The IMPROVED study included 381 seropositive RA patients who were assessed at 4-month intervals over 12 months. Initial treatment with prednisone and methotrexate (MTX) was modified every 4 months to achieve a target disease activity score score below 1.6.

Those who achieved remission at 4 months continued MTX monotherapy, while those that did not were randomized to one of the two treatment arms: DMARD (prednisone, hydroxychloroquine, and sulfasalazine) or adalimumab.

For all rheumatoid autoantibodies assayed, levels decreased from 0 to 4 months and then rose from 4 to 12 months. With treatment escalation, autoantibody levels dropped markedly, and rose during treatment tapering. For instance, RF IgM levels dropped 10% after restarting prednisone and rose 15% after tapering MTX (P<0.0001).

No association was seen between autoantibody levels and DAS scores or EULAR responses over time. In general, changes in autoantibody levels reflect intensity of immunosuppression (escalation or tapering) and not subsequent treatment responses.

Changes in RA-autoantibody levels were not associated with disease activity score or long-term treatment response, but reflected intensity of immunosuppression.

Jack Cush, MD, is the director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Center in Dallas. He is the executive editor of RheumNow.com. A version of this article first appeared on RheumNow, a news, information and commentary site dedicated to the field of rheumatology. Register to receive their free rheumatology newsletter.