{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:52:01Z","timestamp":1790995921305,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study\u00a0aimed to report the safety of avacopan, an oral selective complement C5a receptor antagonist, using pooled data from clinical trials in patients with antineutrophil cytoplasmic antibody (ANCA)\u2013associated vasculitis (granulomatosis with polyangiitis [GPA] or microscopic polyangiitis [MPA]).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were included from two phase 2 (CLEAR [NCT01363388] and CLASSIC [NCT02222155]) and one phase 3 (ADVOCATE [NCT02994927]) double\u2010blind randomized controlled trials comparing the safety and efficacy of avacopan with active non\u2010avacopan control regimens to induce remission in patients with GPA or MPA. In CLEAR and ADVOCATE, avacopan\u2010treated patients received either no or lower doses of study\u2010supplied prednisone than the control groups; in CLASSIC, all groups received the same dose of study\u2010supplied prednisone. Assessments included rates of exposure\u2010adjusted adverse events (AEs), serious AEs (SAEs), and AEs of special interest.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 439 patients with GPA or MPA (avacopan: n = 239; non\u2010avacopan: n = 200) were included. The exposure\u2010adjusted rates of AEs, SAEs, white blood cell (WBC) count reductions, and infections were lower with avacopan versus control (between\u2010group differences in rate per 100 patient\u2010years \u2212151.9 [95% confidence interval (CI) \u2212218.6 to \u221285.3], \u221220.8 [95% CI \u221238.3 to \u22123.3], \u221211.6 [95% CI \u221222.2 to \u22121.2], and \u221224.3 [95% CI \u221248.5 to \u22120.1], respectively). SAEs associated with hepatic function abnormalities occurred in 4.4% of the avacopan group and 2.8% of the control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In clinical trials of GPA or MPA, use of avacopan was associated with fewer AEs, SAEs, and WBC count reductions and fewer infections than non\u2010avacopan treatment. Safety data support the use of avacopan in patients with GPA or MPA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.70001","type":"journal-article","created":{"date-parts":[[2025,4,12]],"date-time":"2025-04-12T17:05:08Z","timestamp":1744477508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Safety of Avacopan for the Treatment of Antineutrophil Cytoplasmic Antibody\u2013Associated Vasculitis: Combined Data From Three Clinical Trials"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9284-7345","authenticated-orcid":false,"given":"Peter A.","family":"Merkel","sequence":"first","affiliation":[{"name":"University of Pennsylvania  Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0398-2308","authenticated-orcid":false,"given":"Michael D.","family":"George","sequence":"additional","affiliation":[{"name":"University of 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