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. 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. 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. Targeting the interleukin-5 receptor with benralizumab, or circulating interleukin-5 with mepolizumab, are effective OGC-sparing strategies in patients with EGPA.
Svenningsen et al. (Mon,) studied this question.
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