Real-world safety assessment of avacopan in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

A total of 3150 avacopan-related adverse event reports were identified from the FDA Adverse Event Reporting System.

• Data source was the FDA Adverse Event Reporting System (FAERS), a postmarketing pharmacovigilance database.
• Disproportionality analysis was conducted to evaluate the significance of avacopan-related AEs at both system organ class (SOC) and preferred terms (PTs) levels.
• This represents postmarketing real-world data following FDA approval of avacopan for AAV.

Disproportionality analysis identified 8 positive SOC signals and 92 positive PT signals for avacopan-related adverse events.

• 92 positive preferred term (PT) signals were detected.
• 34 of the 92 positive PT signals were previously unrecognised adverse events.
• None of the identified signals was classified as a high clinical priority.
• Analysis was conducted at both system organ class (SOC) and preferred terms (PTs) levels.

The median time-to-onset of avacopan-related adverse events was 48 days.

• Time-to-onset (TTO) analysis was performed to explore temporal patterns of AE occurrence.
• Weibull shape parameter (WSP) analysis was also conducted alongside TTO analysis.
• Overall WSP analyses suggested an 'early failure type' pattern for adverse events.
• Event-specific analyses demonstrated heterogeneous temporal patterns across different adverse events.

Hepatobiliary events were the leading adverse events associated with avacopan, with a predominance of reports in female and geriatric patients.

• Hepatobiliary events were the leading SOC-level adverse event signal.
• Reports of hepatobiliary events showed a predominance involving female patients.
• Reports of hepatobiliary events showed a predominance involving geriatric patients (aged ≥65 years).
• Subgroup analyses were undertaken based on gender and age to characterize these differences.

Patients aged ≥65 years had a higher cumulative incidence of adverse events compared to younger patients.

• Subgroup analyses based on age were performed.
• The overall AE risk increased with age.
• Cumulative incidence analyses were performed to explore temporal patterns of AE occurrence.
• The geriatric subgroup (≥65 years) was specifically identified as having elevated risk, particularly for hepatobiliary events.

Avacopan demonstrated a favourable overall safety profile in patients with AAV in real-world settings.

• None of the 92 positive PT signals was classified as a high clinical priority.
• The authors concluded findings 'highlighted the need for risk-informed and AE-specific monitoring strategies to support individualised management.'
• Avacopan is described as 'the first FDA approved drug in a decade' for AAV, making postmarketing safety data particularly important.
• 34 previously unrecognised adverse event signals were identified, suggesting ongoing surveillance is warranted.