TOPLINE

Among patients treated with avacopan, which is approved for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, liver enzyme elevations were uncommon overall, but two patients developed severe drug-induced liver injury that resolved after the drug was discontinued.

METHODOLOGY

• Researchers analyzed data from a US patient registry to estimate real-world rates of liver enzyme elevations and drug-induced liver injury related to avacopan in patients with ANCA-associated vasculitis.
• They included 238 patients (mean age, 59 years; 55% women) who received at least one avacopan prescription between October 2021 and March 2025. Of these, 231 had diagnostic codes for vasculitis.
• Researchers assessed the levels of liver enzymes, including aspartate aminotransferase (AST) or alanine aminotransferase (ALT) above three times the upper limit of normal, alkaline phosphatase above two times the upper limit of normal, and total bilirubin above 2 mg/dL.
• Patients were treated for a median of 353 days, with liver enzymes tested a median of three times, starting about a month after treatment began.
• Lab results were tracked for up to a year after starting treatment, including a 90-day follow-up period after stopping avacopan.

TAKEAWAY

• Overall, five patients had elevated AST levels, three had elevated ALT levels, four had elevated alkaline phosphatase levels, and two had elevated bilirubin levels, with incidence rates ranging from 1.80 to 4.24 per 100 person-years.
• Two cases of drug-induced liver injury were confirmed, both scoring as "highly probable" on a standardized tool for causality assessment.
• The first confirmed case involved severe liver injury, with peak ALT levels reaching 978 U/L and sharp elevations in AST, alkaline phosphatase, and bilirubin levels; a liver biopsy showed mixed portal inflammation with eosinophils.
• Liver enzymes returned to normal within 6 weeks after stopping avacopan in the first confirmed case and within 7 weeks in the second, and neither progressed to vanishing bile duct syndrome.

IN PRACTICE

"Avacopan represents an important therapeutic option for patients with AAV [ANCA-associated vasculitis]; however, these risks should be thoroughly discussed with patients, and routine monitoring timelines, particularly in the first three months, should be scrupulously adhered to," the authors of the study wrote.

SOURCE

The study was led by Eric T. Roberts, PhD, MPH, University of California, San Francisco. It was published online on August 24, 2026, as a brief report in Arthritis & Rheumatology.

LIMITATIONS

Researchers relied on electronic health records for medication data, which may not reflect true estimates. Upper limits of normal for liver function tests were not standardized.

DISCLOSURES

The study received support from the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness registry, Agency for Healthcare Research and Quality, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Two authors reported receiving research grants from various sources. One author reported receiving a research lecture payment from Amgen, along with other industry grants, consulting fees, and royalties from publishing companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.