Real-world incidence of hepatic enzyme elevations and drug-induced liver injury (DILI) among 238 US patients with ANCA-associated vasculitis (AAV) treated with avacopan (October 2021–March 2025), drawn from the RISE Registry.
Liver enzyme elevations were infrequent: AST >3×ULN in 5 patients (4.24/100 person-years), ALT >3×ULN in 3 (2.67/100 person-years), ALP >2×ULN in 4 (3.56/100 person-years), and T.bili >2 mg/dL in 2 (1.80/100 person-years). Two confirmed DILI cases (0.8%) were identified, both with RUCAM scores of 9 (highly probable), including one with histologically confirmed severe hepatocellular injury.
- Small cohort (n=238) limits precision of incidence estimates (wide confidence intervals). - Median time to first enzyme screening was 32 days, with average testing intervals of 125 days — gaps that may cause under-detection of early or transient elevations. - Registry data may not fully capture all laboratory results or patient outcomes outside rheumatology encounters.
Severe DILI, though uncommon, does occur with avacopan — clinicians should initiate liver enzyme monitoring early (within the first month) and maintain regular intervals throughout therapy. Patients should be counseled about hepatotoxicity risk, particularly amid ongoing FDA regulatory review.
