Avacopan in a compassionate use programme for severe anti-neutrophil cytoplasmic antibody-associated vasculitis in...

Avacopan (AVAC), an oral selective C5a receptor inhibitor, has been approved for treatment in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Outside randomized controlled studies, real-world data are scarce. The aim of this study was to provide further insight into the clinical experience of AVAC.

We analysed data from 16 patients with severe AAV included in an AVAC compassionate use programme. Disease activity was estimated with the Birmingham Vasculitis Activity Score (BVAS). Fatigue was assessed using the Multidimensional Assessment of Fatigue (MAF).

Thirteen patients (81%) were diagnosed with granulomatosis with polyangiitis (GPA) and three (19%) with microscopic polyangiitis. The mean age at AVAC initiation was 51 (range 16-74) years. The median [interquartile range (IQR)] BVAS score was 10 (3.25-13.25) at baseline and 0 (0-0) at 6 months (p < 0.0001). All but one reached clinical remission. Prednisolone was tapered from a median (IQR) dose of 25 (20-60) to 2.5 (0-5) mg/day at 6 months (p = 0.0001). Eight patients discontinued prednisolone [median time 2.5 month1 week to 10 months)]. The median (IQR) estimated glomerular filtration rate in patients with renal AAV (n = 10) increased from 50 (13-75) to 58 (15.5-88) mL/min/1.73 m² at 6 months (p = 0.055). One patient progressed to end-stage kidney disease, while another was able to discontinue haemodialysis. Serious adverse events were seen in five of the 16 patients (31.3%). The MAF score decreased, with a mean difference of 6.65 (p = 0.05) at 6 months.

The use of AVAC in a case series with mainly GPA patients led to rapid clinical improvement, reduction of corticosteroid doses, and improvement in fatigue. The findings demonstrate beneficial effects of AVAC as add-on therapy in severe AAV.