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.

Objectives: 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).

Conclusions: 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.