Background/Purpose:

In a recent Phase III study (NCT02020889) in patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA) the anti-interleukin-5 monoclonal antibody mepolizumab showed significant benefit when compared to placebo for both primary endpoints and all secondary endpoints. As not all subjects treated with mepolizumab were able to achieve remission, we investigated post-hoc the benefit in terms of not only remission, but also oral corticosteroid reduction, and/or relapses.

Methods: We conducted a Phase III, randomized, placebo-controlled, double-blind, parallel-group, multi-center study in patients with EGPA and a history of relapsing or refractory disease on stable therapy with prednisolone/prednisone ≥7.5–≤50mg/day with or without additional immunosuppressive therapy for ≥4 weeks. Patients were randomized 1:1 to receive mepolizumab 300mg or placebo subcutaneously, in addition to standard of care, every 4 weeks for 52 weeks. Remission was defined with both the stringent definition utilized in the primary endpoint (Birmingham Vasculitis Activity Score [BVAS]=0, corticosteroid dose ≤4mg/day) as well as the European League Against Rheumatism (EULAR) definition (BVAS=0, corticosteroid dose ≤7.5mg/day). Oral corticosteroid reduction was defined post-hoc as ≥50% reduction from baseline in average prednisolone/prednisone dose during Weeks 48-52. Benefit in relapse was defined post-hoc if a subject was relapse free throughout the 52 week treatment period. We also summarized specific sub-populations of clinical interest: baseline blood eosinophil count <150 cells/μL, oral corticosteroid dose >20 mg/day, and weight >85 kg.

Results: 136 patients received at least one dose of study medication (mepolizumab n=68, placebo n=68). With the primary endpoint definition of remission the results showed that 53 (78%) subjects in the mepolizumab group received clinical benefit in terms of remission and/or a 50% reduction in oral corticosteroid dose and/or having no relapses during the study treatment period, compared with 22 (32%) subjects in the placebo group. For the EULAR definition of remission 59 (87%) subjects in the mepolizumab group received clinical benefit compared with 36 (53%) subjects in the placebo group. In all of the sub-populations described, clinical benefit was seen in greater percentages of subjects treated with mepolizumab compared to placebo.

Conclusion: Using a broader yet clinically relevant definition of response that includes remission, absence of relapse, and/or steroid reduction, a significantly greater proportion of mepolizumab treated patients experienced clinical benefit when compared to placebo. In addition, more subjects in sub-populations of interest experienced clinical benefit with mepolizumab treatment compared to placebo. (Funded by GSK [Study 115921] in collaboration with NIAID [U01 AI097073] and the Division of Intramural Research, NIAID, NIH).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/mepolizumab-for-the-treatment-of-patients-with-eosinophilic-granulomatosis-with-polyangiitis-post-hoc-results-of-a-phase-iii-randomized-placebo-controlled-trial/