The Effect of Benralizumab and Mepolizumab on Use of Oral Glucocorticoids in Patients With Eosinophilic Granulomatosis With Polyangiitis

OBJECTIVE: The phase 3 MANDARA study demonstrated noninferiority 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). The objectives of this post hoc analyses are to further elucidate the efficacy of benralizumab and mepolizumab in facilitating reductions in OGCs through investigating timings and sustainability of reducing OGCs as well as the cumulative use of OGCs. METHODS: Adults with EGPA requiring ≥7.5 mg/day OGC with or without immunosuppressive therapy were randomized to benralizumab 30 mg (n = 70) or mepolizumab 300 mg (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 ≤4 mg/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 approximately 1,800 mg in both groups. At weeks 49 to 52, the median OGC dose was 1.16 (minimum-maximum 0.0-16.6) and 3.00 (minimum-maximum 0.0-25.7) mg/day for benralizumab and mepolizumab, respectively. Time to first or sustained OGC reduction to ≤4 mg/day or by ≥50% and accrued OGC-free duration were similar between groups. More benralizumab- than mepolizumab-treated patients completely withdrew OGCs (33 of 70 vs 20 of 70; hazard ratio [HR] for the time to the first complete withdrawal 1.84 [95% confidence interval [CI] 1.06-3.27]; unstratified log-rank test P = 0.0291) and sustained complete withdrawal (17 of 70 vs 7 of 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 antineutrophilic cytoplasmic antibody 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.