Autoantibodies Predict Response to RA Treatment

September 18, 2015

Abatacept performs well in rheumatoid arthritis patients who are positive for anti-citrullinated protein antibodies.

Rheumatoid arthritis patients who are positive for anti-citrullinated protein antibodies (ACPA) may show an overall better response to treatment with the fusion protein abatacept than with the human monoclonal antibody adalimumab, although both drugs lead to treatment responses in these patients, according to anew post-hoc analysis. In an exploratory analysis published in the Sept. 10 online issue of the Annals of the Rheumatic Diseases, the researchers, led by Jeremy Sokolove, MD, of Stanford University in Stanford, Calif., found that improvements in Disease Activity Scores in 28 joints were significantly less at two years in ACPA-negative patients given either drug than in those who were seropositive among patients in the 2-year AMPLE trial.

For those receiving abatacept, the mean improvement in DAS28 at two years was significantly higher for those in the highest quartile of ACPA concentration than in the 3 lower quartiles. However, for adalimumab, DAS28 improvements were similar for all ACPA quartiles. Anti-citrullinated protein antibodies are a sensitive, highly specific biomarker for rheumatoid arthritis, but their clinical relevance remains unclear. They can be present for years prior to the onset of RA in at-risk individuals. In fact, 70-80% of rheumatoid arthritis patients are ACPA positive. There have been suggestions they can be used to predict a more severe disease course with more erosive disease, the researchers noted. As disease develops, the concentration of anti-citrullinated protein antibodies increases, expands and isotype usage evolves. But the relationship between the concentration of ACPA and response to therapy is not yet fully understood.  “The improved clinical efficacy in anti-CCP2-positive versus anti-CCP2-negative patients for both adalimumab and abatacept suggests that ACPA status may be a relevant factor in predicting treatment response,” they stated. AMPLE was a phase III clinical trial that randomized patients with active rheumatoid arthritis and an inadequate response to methotrexate to subcutaneous abatacept 125 mg per week or adalimumab 40 mg every other week, plus methotrexate, for two years. Baseline serum samples were available for 508 patients; three-quarters of them were ACPA positive. Similar numbers of patients were in each quartile of ACPA concentration. Baseline characteristics of the four quartiles were not significantly different. At 1 year, a 20% response on American College of Rheumatology (ACR20) criteria was seen in 64.8% of patients in the abatacept group and in 63.4% in the adalimumab group. ACR20 responses were similar after two years. The reason for a slightly different pattern of response between abatacept and adalimumab is unknown, but may be due to the different mechanisms of action of the two drugs, the researchers stated. Abatacept is a selective T-cell costimulatory factor, while adalimumab is a tumor necrosis factor inhibitor.  

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References:

Sokolove J., Schiff M., et al.

Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial.Annals of the Rheumatic.

Sept. 10, 2015. doi:10.1136/annrheumdis-2015-207942