TOPLINE:

A postmarketing analysis of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis receiving avacopan in real-world settings identified 92 adverse event (AE) signals, with hepatobiliary events and drug-induced liver injury reported more often in female patients than in male patients. Patients aged 65 years or older had a higher cumulative incidence of AEs than patients younger than 65 years.

METHODOLOGY:

• Researchers analyzed AEs associated with avacopan in patients with ANCA-associated vasculitis during the drug’s postmarketing period using data from the FDA Adverse Event Reporting System (FAERS), which is now called the Adverse Event Monitoring System.
• They identified 3150 reports with avacopan as the primary suspect drug, with most submissions originating from the US (76.3%), followed by Japan (12.7%), the UK (3.2%), Canada (3.0%), and France (1.5%).
• Disproportionality analysis (DPA) was conducted to evaluate the significance of avacopan-related AEs at both system organ class and preferred term levels.
• Time-to-onset and Weibull shape parameter (WSP) analyses were performed to explore temporal patterns of AE occurrence, with subgroup analyses by sex and age (patients aged < 65 years vs ≥ 65 years).
• Detected signals were compared with the US prescribing information and the ADVOCATE trial.

TAKEAWAY:

• Of 26 system organ classes, hepatobiliary disorders and surgical and medical procedures met the two criteria of all DPA algorithms. Several other classes, such as gastrointestinal disorders; infections and infestations; renal and urinary disorders; respiratory, thoracic, and mediastinal disorders; and vascular disorders, met at least one of the criteria.
• Overall, 92 positive preferred term signals were associated with avacopan. Researchers identified 34 previously unrecognized preferred terms not reported in the ADVOCATE trial, and none were classified as high clinical priority.
• The median time-to-onset for reported AEs was 48 days, with 35.9% of AE reports occurring within the first 30 days and WSP analysis revealing a pattern of early failure, suggesting a higher risk for AEs early in treatment.
• Hepatobiliary events were reported more frequently in patients aged 65 years or older than in those younger than 65 years (114 vs 33 cases) and in female patients vs male patients (105 vs 47 cases), with a similar pattern noted for drug-induced liver injury. The cumulative incidence of total AEs was higher in patients aged 65 years or older than in those younger than 65 years (P < .0001), whereas no significant difference was observed between male and female patients.

IN PRACTICE:

“These findings underscore the need for vigilant and individualized safety monitoring throughout the treatment course, guided by the distinct temporal patterns of different AEs. Clinicians should remain alert to both known and previously unrecognized AEs to optimize the safety of avacopan therapy in [ANCA-associated vasculitis] treatment,” the authors wrote.

SOURCE:

This study was led by Xiang-Yu Han, Peking University First Hospital in Beijing, China. It was published online on March 25, 2026, as a short report in RMD Open.

LIMITATIONS:

The FAERS system relied on spontaneous and voluntary reports, which may have led to underreporting, delays, and inconsistencies in data quality. The positive signals detected by the DPA algorithm may have indicated a statistical association rather than established causal links.

DISCLOSURES:

This research was supported by grants from the National Key Research and Development Program, National Natural Science Fund, National High Level Hospital Clinical Research Funding, and other sources. No relevant competing interests were reported by the authors.

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