The pooled analysis aimed to evaluate the safety profile of avacopan, a complement C5a receptor inhibitor, in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).
Data were aggregated from two phase 2 trials (NCT01363388, NCT02222155) and one phase 3 trial (NCT02994927), encompassing 439 participants (239 avacopan; 200 glucocorticoid-based therapy). Participants received standard induction therapy with rituximab or cyclophosphamide alongside either avacopan or oral glucocorticoids.
The primary safety endpoints included exposure-adjusted rates of adverse events (AEs), serious adverse events (SAEs), infections, hematologic and hepatic toxicities, and hypersensitivity reactions, reported per 100 patient- years (PYs). Avacopan demonstrated lower rates of total AEs (1099.8 vs 1251.7), infections (142.2 vs 166.6), and neutropenia/leukopenia (22.6 vs 34.2) per 100 PYs. SAEs were also reduced (70.7 vs 91.5).
Grade 4 lymphopenia was less frequent with avacopan (2.4% vs 8.0%), although hepatic SAEs were marginally higher (4.4% vs 2.8%). Hospitalization duration was shorter (11.7 vs 17.6 days). The research findings suggest that avacopan offers a favorable safety profile and represents a glucocorticoid- sparing advancement in AAV management.
However, limitations include variable glucocorticoid dosing and reporting heterogeneity across trials.
