- Design
- Retrospective registry cohort with causality assessment
- Population
- 238 US patients with ANCA-associated vasculitis prescribed avacopan
- Primary outcome
- Hepatic enzyme elevation and confirmed drug-induced liver injury
- Effect
- 2 highly probable DILI cases (0.8%); AST >3× ULN 4.24 per 100 person-years
Avacopan, an oral C5a receptor inhibitor, was approved in 2021 for ANCA-associated vasculitis. The paper reports that after 76 worldwide cases of drug-induced liver injury, FDA requested market withdrawal and the manufacturer declined. This study used the US RISE registry to estimate real-world liver risk.
Among 238 patients prescribed avacopan from 2021 to 2025, enzyme elevations were uncommon: AST above three times normal at 4.2 per 100 person-years, ALT 2.7, alkaline phosphatase 3.6 and bilirubin 1.8. Two patients (0.8%) had drug-induced liver injury with RUCAM scores of 9 (highly probable), one with severe hepatocellular injury on histology. The first liver test came at a median of 32 days, and tests averaged 125 days apart.
The drug's regulatory position is under reassessment, and the monitoring seen here is sparser than the risk warrants. Its status and availability in India are not known to us.
- Check liver function before starting avacopan.
- Test liver function about every 4 weeks for the first six months — not every four months, as happened here.
- Stop avacopan promptly if transaminases or bilirubin rise significantly.
- Discuss the liver risk and the regulatory uncertainty with patients at consent.
Why it matters
Severe liver injury is rare but real, and real-world monitoring is too infrequent to catch it early.
Don't overread it
Two cases in 238 patients give an imprecise rate; the study cannot compare avacopan's risk with glucocorticoid-based regimens.
The statistics, in plain English
Incidence per 100 person-years is how many events would occur if 100 patients took the drug for a year. The intervals are wide — ALT elevation could be anywhere from about 1 to 8 per 100 person-years — because events were few.
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