Serial ANCA titers: Useful tool for prevention of relapses in ANCA-associated vasculitis

Background. The value of measuring serial antineutrophil cytoplasmic autoantibody (ANCA) titers in guiding therapy among patients with ANCA-associated vasculitis is controversial. Methods. We measured serial titers of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA by antigen-specific enzyme-linked immunosorbent assays (ELISAs) in 48 patients with ANCA-associated vasculitis who were followed up during remission at the Massachusetts General Hospital from 1990 through 2000 (mean follow-up, 46.2 months). We retrospectively assessed disease activity by Birmingham Vasculitis Activity Score (BVAS). Results. We found 21 episodes of fourfold or greater ANCA titer rises in 17 patients who were in complete remission (BVAS = 0). Among eight patients who had 10 such titer rises and were not given increased immunosuppression, (group I), all suffered relapses after each episode (mean interval, 5.8 months), whereas among 11 patients, each with one titer rise, who received preemptive increased immunosuppression, (group II), only two relapses occurred, at 3 and 6 months. The difference in the cumulative incidence of relapses in a 1-year period between the two groups was 82% (P = 0.0002). Changes in ANCA titers were also used to help guide therapy in the other 31 patients in the study; patients with slight titer rises often received incremental increases in immunosuppression, whereas those with falling titers received incremental decreases. The overall outcome in the entire group was favorable; 46 patients were alive at the end of the study; two died of unrelated diseases. Conclusion. Serial measurements of PR3- and MPO-ANCA titers in patients with ANCA-associated vasculitis during remission can help predict relapses, and preemptive increases in immunosuppression following fourfold titer rises reduces the risk of relapses. Moreover, adjustment of immunosuppression based on lesser titer changes appears to result in a favorable outcome.