Background/Purpose: The combination of immunosuppressants and glucocorticoid is recommended for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, adverse events of immunosuppressants sometimes hamper the sufficient therapy. Clarification of adverse events, comparison of the incidence, and the outcome of re-administrations among immunosuppressants were the aims of the study.

Methods: The data of AAV-patients from 2005 to 2016 in our hospital were analyzed retrospectively. They included patients-demographics, ANCA subtype, use of immunosuppressants, the adverse events that caused their discontinuation, and the outcome of their re-administration.

Results: 162 patients were found to have AAV during that time; 132 were positive for myeloperoxidase-ANCA, 25 for proteinase 3-ANCA, and 5 for both. Among 162 patients, 93 (57.4%) were treated with both glucocorticoid and immunosuppressants. In 38 of 93 (40.9%), 44 immunosuppressants were discontinued due to adverse events; 3 patients received 2 immunosuppressants and 1 patient received 4 in the course of the treatment. Median (min.-max.) time from beginning to stopping immunosuppressants was 0.9 (0.3-96) months. 75.0% of the patients with kidney involvement and 38.6% of the patients without it discontinued immunosuppressants (p = 0.003, Chi-square test). The immunosuppressants discontinued were cyclophosphamide in 24 (54.4%), azathioprine in 6 (13.6%), mizoribine in 4 (9.1%), methotrexate in 3 (6.8%), rituximab in 2 (4.5%), and others in 5 times (11.6%). The adverse events were 21 infections (42.9%), 13 cytopenias (26.5%), 6 hepatotoxities (12.2%), and 9 others (28.4%); 7 patients experienced 2 adverse events and 1 patient experienced 5. The infection included reactivation of cytomegalovirus (42.9%), respiratory tract infections (33.3%), sepsis (9.5%), and others (8.7%). The incidence of adverse events of cyclophosphamide, azathioprine, mizoribine, methotrexate, and rituximab was 31.6%, 21.4%, 23.5%, 17.6%, and 20.0%, respectively (p = 0.75, Fisher’s exact test). The types of adverse events were different among immunosuppressants; infection and cytopenia, hepatotoxity, and sepsis were most common in cyclophosphamide, azathioprine, and mizoribine, respectively. Among 38 patients who discontinued immunosuppressants, 11 were re-administered the same drugs (28.9%), 14 others (36.8%), and 13 none (34.2%). Median (min.-max.) time to re-administration was 2.0 (0-60) months.

Conclusion: The discontinuation of immunosuppressants due to adverse events was not rare in AAV-patients. One third of the patients who discontinued immunosuppressants were re-administered the same drugs without serious outcomes after recovery from adverse events. Kidney involvement was a risk of IS discontinuation and close monitoring of kidney involvement was mandatory in AAV-patients on immunosuppressants. Although no difference was observed in the incidence of adverse events, clinical presentation of adverse events was diverse among immunosuppressants.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/adverse-events-for-discontinuation-of-immunosuppressants-and-outcome-of-their-re-administration-in-patients-with-antineutrophil-cytoplasmic-antibody-associated-vasculitis-a-single-center-study-in-jap/