Résumé
Objective The Phase 3 MANDARA study demonstrated non‐inferiority of benralizumab versus mepolizumab for remission in patients with eosinophilic granulomatosis with polyangiitis (EGPA). More benralizumab‐treated patients achieved complete withdrawal of oral glucocorticoids (OGCs). These post‐hoc analyses further elucidate the efficacy of benralizumab and mepolizumab in facilitating reductions in OGCs. Methods Adults with EGPA requiring ≥7.5 mg/day OGC ±immunosuppressive therapy were randomized to benralizumab 30mg (n=70) or mepolizumab 300mg (n=70) subcutaneously every 4 weeks for 52 weeks. Investigators tapered OGCs for patients with stable EGPA based on clinical judgment. Reductions in OGC use (to ≤4mg/day, by ≥50%, or complete withdrawal) were considered sustained if achieved by Week 40 and maintained through Week 52. Results The 12‐month cumulative dose of OGC was ~1,800 mg in both groups. At Weeks 49‐52, the median (minimum‐maximum) OGC dose was 1.16 (0.0–16.6) and 3.00 (0.0–25.7) mg/day for benralizumab and mepolizumab, respectively. Time to first or sustained OGC reduction to ≤4mg/day or by ≥50%, and accrued OGC‐free duration, were similar between groups. More benralizumab‐ than mepolizumab‐treated patients completely withdrew OGCs (33/70 vs 20/70; HR for time to first complete withdrawal 1.84 [95% CI, 1.06, 3.27], unstratified log‐rank test p=0.0291) and sustained complete withdrawal (17/70 vs 7/70; HR for time to reduction 2.97 [95%CI: 1.26,7.77], unstratified log‐rank test p=0.0268). In both groups, complete OGC withdrawal was similar across patient subgroups, including by ANCA status and immunosuppressive use. Conclusion Targeting the interleukin‐5 receptor with benralizumab, or circulating interleukin‐5 with mepolizumab, are effective OGC‐sparing strategies in patients with EGPA.