{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:23:16Z","timestamp":1791217396340,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K24 AR074534"],"award-info":[{"award-number":["K24 AR074534"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"publisher","award":["R01 HS028024"],"award-info":[{"award-number":["R01 HS028024"]}],"id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp;amp; Rheumatology"],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Avacopan, an oral C5a receptor inhibitor, was approved for antineutrophil cytoplasmic antibody\u2013associated vasculitis (AAV) in 2021. Following US Food and Drug Administration (FDA) reports of 76 worldwide drug\u2010induced liver injury (DILI) cases (66 in Japan and five in the United States), the agency requested market withdrawal, which the manufacturer declined. US risk has not been quantified using real\u2010world data. This study estimated the incidence of hepatic enzyme elevations among US avacopan users and characterized confirmed DILI cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data came from the Rheumatology Informatics System for Effectiveness registry. We identified patients with AAV with at least one avacopan prescription (October 2021\u2013March 2025). Hepatic enzyme elevations were defined per FDA guidance (aspartate transferase [AST] or alanine transaminase [ALT] &gt;3 \u00d7 the upper limit of normal [ULN], alkaline phosphatase [Alk Phos] &gt;2 \u00d7 ULN, and total bilirubin &gt;2 mg\/dL). Person\u2010time at risk was estimated from prescribing information. Patients meeting elevated laboratory thresholds underwent Roussel Uclaf Causality Assessment Method (RUCAM) evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 238 patients with AAV treated with avacopan, liver enzyme elevations during treatment were uncommon: five patients had elevated AST, three ALT, four Alk Phos, and two total bilirubin, with incidence rates of 4.24 (95% confidence interval [CI] 1.77\u201310.19), 2.67 (95% CI 0.86\u20138.27), 3.56 (95% CI 1.34\u20139.49), and 1.80 (95% CI 0.45\u20137.19) per 100 person\u2010years, respectively. Median time to first hepatic enzyme screening was 32 days, with testing intervals averaging 125 days. Two DILI cases (0.8%) were identified, both with RUCAM scores of 9 (highly probable causality), including one with histologically confirmed severe hepatocellular injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Hepatic enzyme elevations during avacopan therapy were infrequent in this US cohort, yet severe DILI occurred. Findings support vigilant early monitoring and informed discussions of potential risks during ongoing regulatory reassessment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70304","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:39:55Z","timestamp":1787571595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hepatotoxicity of Avacopan: Real\u2010World Incidence and Confirmed Cases of Severe Drug\u2010Induced Liver Injury in a\n                    <scp>US<\/scp>\n                    National Rheumatology Registry"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8435-8994","authenticated-orcid":false,"given":"Eric T.","family":"Roberts","sequence":"first","affiliation":[{"name":"Division of Rheumatology University of California  San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Dadabhoy","sequence":"additional","affiliation":[{"name":"Northwest Rheumatology Specialists  Elk Grove Village Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Antolini","sequence":"additional","affiliation":[{"name":"Denver Arthritis Clinic  Denver Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2238-2287","authenticated-orcid":false,"given":"Sharon A.","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of California  San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-5043","authenticated-orcid":false,"given":"Gabriela","family":"Schmajuk","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of California  San Francisco"},{"name":"San Francisco Veterans Affairs Medical Center  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3508-4094","authenticated-orcid":false,"given":"Jinoos","family":"Yazdany","sequence":"additional","affiliation":[{"name":"Division of Rheumatology University of California  San Francisco"},{"name":"Zuckerberg San Francisco General Hospital  San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"issue":"83","key":"e_1_2_7_2_1","first-page":"23278","article-title":"91 FR 23278 \u2010 ChemoCentryx, Inc.; proposal to withdraw approval of new drug application for TAVNEOS (avacopan) capsule, 10 milligrams; opportunity for a hearing","volume":"91","author":"US Food and Drug Administration","year":"2026","journal-title":"Fed Regist"},{"key":"e_1_2_7_3_1","unstructured":"European Commission.Notification to the CHMP\/EMA secretariat of a referral under article 20 of regulation (EC) 726\/2004. January 29 2026. Accessed March 19 2026.https:\/\/www.ema.europa.eu\/en\/documents\/referral\/tavneos\u2010article\u201020\u2010procedure\u2010notification_en.pdf"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2608684"},{"key":"e_1_2_7_5_1","unstructured":"US Food and Drug Administration.FDA identifies cases of serious liver injury in patients taking tavneos (avacopan) for severe active anti\u2010neutrophil cytoplasmic autoantibody (ANCA)\u2010associated vasculitis. EIN Presswire. March 31 2026. Accessed March 31 2026.https:\/\/www.einpresswire.com\/article\/903012948\/fda\u2010identifies\u2010cases\u2010of\u2010serious\u2010liver\u2010injury\u2010in\u2010patients\u2010taking\u2010tavneos\u2010avacopan\u2010for\u2010severe\u2010active\u2010anti\u2010neutrophil\u2010cytoplasmic\u2010autoantibody"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22294"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.58"},{"key":"e_1_2_7_8_1","volume-title":"LiverTox: Clinical and Research Information on Drug\u2010Induced Liver Injury","author":"National Institute of Diabetes and Digestive and Kidney Diseases","year":"2012"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae689"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead285"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s41927-025-00456-4"},{"key":"e_1_2_7_12_1","unstructured":"Pharmaceuticals and Medical Devices Agency Japan.Investigation Results on Avacopan. May 21 2026. Accessed July 9 2026.https:\/\/www.pmda.go.jp\/files\/000280786.pdf"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.101378"},{"issue":"9","key":"e_1_2_7_14_1","article-title":"Rare clinically significant methotrexate toxicity despite frequent laboratory abnormalities: a population\u2010based study of methotrexate monitoring [abstract]","volume":"77","author":"Reed G","year":"2025","journal-title":"Arthritis Rhuematol"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1155\/ijcp\/6035774"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.17914"}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70304","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.70304","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.70304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T07:11:15Z","timestamp":1788246675000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.70304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":15,"alternative-id":["10.1002\/art.70304"],"URL":"https:\/\/doi.org\/10.1002\/art.70304","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2026-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"art.70304"}}