Background/Purpose: Mepolizumab (MPZ), an anti–interleukin-5 monoclonal antibody, has shown efficacy in reducing glucocorticoid (GC) dosage and sustaining remission in eosinophilic granulomatosis with polyangiitis (EGPA). This study investigated real-world outcomes of GC and immunosuppressant (IS) discontinuation, and the clinical predictors of successful shift to MPZ monotherapy.

Methods: We conducted a retrospective cohort study of 35 EGPA patients treated with MPZ and GC for ≥48 weeks. Patients were stratified by antineutrophil cytoplasmic antibody (ANCA) status and IS use. Outcomes included the proportion of patients achieving GC ≤4 mg/day and GC/IS discontinuation. GC exposure, time to withdrawal, and predictors were analyzed using Wilcoxon signed-rank, Mann–Whitney U, log-rank tests, and Cox proportional hazards models. Correlations were assessed by Spearman’s coefficient.

Results: All patients (35/35) achieved GC tapering to ≤4 mg/day. GC was completely discontinued in 29 patients (83%), and 13 (37%) discontinued both GC and IS, achieving sustained MPZ monotherapy. The median time to GC-free status was 579 days (95% CI: 63–1094), while the median time to IS-free status was 2161 days (95% CI: 1054–3267). A significant negative correlation was observed between time from GC initiation to MPZ initiation and total GC duration (ρ = 0.691, p < 0.001), suggesting the benefit of early MPZ initiation. ANCA-negative patients achieved GC-free status more rapidly than ANCA-positive patients (p = 0.038). IS use did not significantly affect GC discontinuation time, though non-IS users tended to discontinue GC earlier (p = 0.040).Univariate Cox regression identified female sex (HR 2.2, 95% CI: 1.0–4.5, p = 0.007), absence of neurological involvement (HR 0.3, 95% CI: 0.1–0.8, p = 0.021), and no history of relapse (HR 0.4, 95% CI: 0.2–0.9, p = 0.036) as significant predictors of GC/IS discontinuation. In multivariate analysis, neurological involvement remained an independent predictor (HR 0.3, 95% CI: 0.12–0.9, p = 0.035).

Conclusion: MPZ facilitated tapering to low-dose GC in all patients and enabled complete GC discontinuation in the majority, with some patients achieving IS-free status. Early MPZ initiation significantly shortened GC exposure. ANCA-negative status and absence of neurological involvement were associated with more favorable outcomes. These findings support the treatment with MPZ monotherapy as a feasible long-term treatment strategy in selected EGPA patients.

Glucocorticoid and Immunosuppressant-Free Outcomes with Mepolizumab in EGPA (n = 35)

Correlation Between Time to Mepolizumab Initiation and Total Glucocorticoid Exposure

Predictors of Combined Glucocorticoid and Immunosuppressant Discontinuation Under Mepolizumab Monotherapy

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/early-mepolizumab-initiation-enables-high-glucocorticoid-and-immunosuppressant-discontinuation-rates-in-egpa-a-retrospective-cohort-study-of-35-patients/