Evolution of Anti-citrullinated Protein Antibodies in Rheumatoid Arthritis Patients Under Disease-Modifying Therapy: A Prospective Cohort Study

Introduction The primary objective of our study was to describe the variation of anti-citrullinated protein antibodies (ACPA) antibody levels in patients with rheumatoid arthritis (RA) under disease-modifying therapy. The secondary objectives were to evaluate the variation of ACPA levels according to disease activity and to determine the characteristics of patients who have negative ACPA. Methods It was a prospective study including patients with ACPA-positive RA treated with disease-modifying antirheumatic drugs (DMARDs) and having a Disease Activity Score (DAS) greater than 2.6, indicating at least low disease activity or higher. A medical checkup including a clinical evaluation, an inflammatory test, and a measurement of ACPA levels using the enzyme-linked immunosorbent assay (ELISA) was performed for each patient at M0, M6, and M12. Two groups were defined: the rituximab (RTX) group, consisting of patients treated with RTX, and the no-RTX group, which included patients receiving other therapies, such as tumor necrosis factor inhibitors (TNFi) and interleukin 6 inhibitors (anti-IL6) or conventional disease-modifying antirheumatic drugs (csDMARDs). Results Ninety ACPA-positive RA patients were included. Seventy-seven (85.6%) were female and the mean age was 54.96 ± 13.13 years. The median disease duration was 11 years, and the baseline Disease Activity Score 28-C-reactive protein (DAS28-CRP) was 4.35 ± 0.99. Forty-eight (53.3%) of patients were already on RTX. The median ACPA level at baseline was 186 IU/ml (74-200), showing a significant decline over time (M0: 186 (74-200); M6: 111 (59-195); M12: 95 (45-195); p<0.001). This reduction was significant in the RTX group (ACPA M0: 191 (70-200); ACPA M6: 96 (33-195); ACPA M12: 75 (17-147); p<0.001) but not in the no-RTX group (ACPA M0: 156 (68-200); ACPA M6: 121 (70-195); ACPA M12: 175 (67-200); p=0.26). At M12, 27 (30%) patients achieved remission based on the DAS28 score. Their median ACPA level was 157 IU/ml (75-200) at baseline, which significantly decreased over time (p<0.001). When analyzing the delta ACPA, it was significantly larger in the RTX group (p<0.001). Conclusion In this real-life study, ACPA antibody levels decreased significantly in RA patients who had received RTX. This could suggest the possibility of achieving immunological remission with biotherapy, more specifically with RTX.