C5a receptor inhibition and minimal steroids for induction of remission in ANCA-associated vasculitis

BACKGROUND AND HYPOTHESIS: C5a receptor (C5aR) inhibition with avacopan has enabled cumulative glucocorticoid (GC) dose reduction in ANCA-associated vasculitis (AAV); however, real-world steroid use remains high. This study evaluates a minimal-GC plus avacopan-based regimen against standard-of-care GC for clinical efficacy, renal recovery, urinary biomarkers, and patient-reported outcomes (AAV-PRO). We hypothesised that this regimen would permit substantial GC reduction while maintaining clinical disease control and renal recovery. METHODS: This two-centre retrospective study included 126 patients with newly diagnosed or relapsing AAV (70 avacopan; 56 GC). The avacopan group followed the minimal-GC plus avacopan-based regimen: prednisolone 30 mg daily for one week, then 20 mg for one week, with no protocolised upfront intravenous methylprednisolone; the GC group received a standard high-dose oral GC taper (from 1 mg/kg, capped at 60 mg/day). Both received standard induction with rituximab or cyclophosphamide. Outcomes included 12-month sustained remission, eGFR change, safety, AAV-PRO scores, and urinary sCD163, MCP-1 and C5a trajectories. RESULTS: Baseline characteristics were comparable, with median presenting eGFR 23 versus 25 mL/min/1.73 m² (P = 0.31). Median 12-month cumulative prednisolone was 390 mg with avacopan versus 3535 mg with GC (P < 0.001). Observed sustained remission was 93% versus 91% (P = 0.75) and relapse 6% versus 11% (P = 0.30). Median eGFR increase was 20 versus 18 mL/min/1.73 m² (P = 0.32), with no significant difference among those presenting with eGFR < 15 (P = 0.20). Severe infection rates did not differ significantly (6% versus 9%). AAV-PRO scores were significantly lower with avacopan (median 97 versus 197; P = 0.04). No significant between-group difference in biomarker trajectories was detected. CONCLUSIONS: In this observational cohort, the minimal-GC plus avacopan-based regimen showed no statistically significant differences in clinical or renal outcomes versus high-dose steroids while reducing cumulative GC exposure by ∼90%. These real-world observations support the feasibility of substantial upfront GC minimisation but should be regarded as supportive rather than confirmatory.