Avacopan with combined cyclophosphamide and rituximab for induction therapy in severe ANCA-associated vasculitis: retrospective observational study of 30 patients in two German referral centres

Abstract

Objective Combination therapy of rituximab (RTX) and cyclophosphamide (CYC) can be considered for the induction of remission in severe anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). The presented study reports on the safety and efficacy of the complement C5a receptor inhibition with avacopan in the patients with severe ANCA-associated vasculitis treated with RTX and CYC in combination. Methods Retrospective analysis of the clinical course, response to and safety of avacopan in combination with RTX and CYC in 30 patients with severe ANCA-associated vasculitis with renal and at least two further organ-threatening involvement treated in two German referral centres. Results The median observation time was 49 weeks (range 26-52). All patients achieved remission by week 24. Mean BVAS score was 22.8 (range 12-53) at baseline; mean eGFR increased from 44.0 ml/min per 1.73m2 at baseline to 57.6 ml/min per 1.73m2 by week 52. GC comedication was discontinued in 17 of 29 (58.6%) patients by week 24, and in 23 of 28 (82.1%) by week 52. One patient discontinued avacopan treatment due to urosepsis, another due to refractory disease. There was a significant difference in dialysis dependency of GC-free patients versus GC-treated patients at week 24 (n=1 vs. 4, p=0.048, OR 0.12, CI:0.01-1.25). Conclusion In this observational study, avacopan as GC-sparing agent appeared safe and efficacious in combination with RTX and CYC for remission induction in severe ANCA-associated vasculitis. In this subgroup, prospective studies are needed to determine the efficacy and safety of avacopan in combination with RTX and CYC for guidance of a GC-sparing strategy.