Background: The novel therapeutic principle of complement C5 inhibition by avacopan was approved for the treatment of ANCA-associated vasculitis (AAV), in particular for granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in the combination of rituximab (RTX) or Cyclophosphamide (CYC). Hoewever, the AVV patients suffering from severe course of disease with several potentially life-threatening or organ-threatening manifestations can benefit from the combined use of RTX and CYC.

Objectives: Against this background, we present here the retrospective observational study which observed AAV patients (with GPA or MPA) suffering from histologic proven renal impairment together with other organ-threatening manifestations after they received the combination therapy of RTX with CYC and avacopan.

Methods: Between February 2022 and December 2023, a retrospective two-centre study from two centres in Germany (RUB University Hospital Minden JWK and Holstein University Hospital Luebeck) included 30 patients with AAV who were treated with an intensified treatment regimen with the combination of CYC, RTX, and avacopan together with glucocorticoids in a tapering dosage. The combination therapy of CYC and RTX was administered analogously to the RITUXIVAS protocol (n=13) or CycLowVas protocol (n=17). The median observation time was 40 weeks (8-52), the evaluation according to subgroups of AAV patients was stratified into the two groups of the successful versus non-successful termination of GC up to the 24th week after the start of therapy with CYC/RTX.

Results: Of the 30 AAV patients included in the study (Table 1), 26 patients were observed over 24 weeks, of whom 12 (46.2%) were GC-free (Figure 1). Three patients discontinued treatment with avacopan: one patient with urosepsis (week 8), one patient with refractory disease prior to plasmapheresis (week 32), and one patient because of his incompliance with the treatment recommendation (week 48). Significantly lower initial BVAS was associated with successful termination of GC therapy (27.7 vs. 19.7, p=0.010), the hemodialysis dependency of GC-free patients were rarer than in the patients who still needed GC (OR 0.13, CI 0.01-1.33). Only 7 of 26 patients (at week 24) showed an AAV damage score (according to VDI) greater than 1.

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Figure 1.

survival of AVV patients on avacopan and glucocorticoids over 52 weeks

Conclusion: The observational study suggests that combination therapy with RTX/CYC together with avacopan appears to be well promising in the selected AAV patient population. However, controlled prospective studies investigating treatment efficacy of the combination of RTX/CYC as well as avacopan have to be considered to confirm the results.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Gunter Assmann Boehringer Inglheim, UCB, AbbVie, Vifor Pharma, Astrazeneca, Novartis, Adjailia El-Baraa: None declared, Korsten Peter Astrazeneca, UCB, Boehringer-Inglheim, AbbVie, Novartis, Turkiewicz Ryszard MSD, BMS, Boehringer-Inglheim, Janssen, Radermacher Joerg: None declared, Michael Schmidt: None declared, Peter Lamprecht Astrazeneca, GSK, Novartis, Vifor Pharma., BMBF, DFG, DGRh, John Grube Foundation, Vifor Pharma. Consulating fees: Astrazeneca, Novartis, Vifor Pharma.