Mepolizumab Demonstrates Real-world Clinical Effectiveness in both Type 2 Biomarker High and Type 2 Biomarker Low Patients with Severe Asthma

Abstract

Rationale: Mepolizumab, an anti-IL-5 monoclonal antibody, is a precision therapy for eosinophilic severe asthma. The mepolizumab RCTs in severe asthma suggested a baseline blood eosinophil threshold of 150 cells/μL to identify responders for beneficial exacerbation reduction response. Methods: The applicability of this threshold was evaluated in two real-world experience data sets, REALITI-A, a prospective international database study (n=822) and REDES a retrospective national database study (n=318). Both studies were observational studies in adults with severe asthma in whom a physician had initiated treatment with mepolizumab 100 mg subcutaneous. The primary endpoint was the rate of clinically significant asthma exacerbations (CSE; requiring the use of systemic corticosteroids or hospital/emergency department admission) between the 12 months prior to (before treatment) and after initiating mepolizumab treatment. The CSE reduction in the year after starting mepolizumab was evaluated in relationship to categories of progressively increasing baseline pre-treatment blood eosinophil counts (cells/μL), with ranges from <150, through to ≥500 (REALITI-A) and <150 through to ≥700 (REDES). Results: Mepolizumab significantly reduced total CSE in REALITI-A (with a 71% reduction) and REDES (77.5% reduction) from respective mean pre-treatment annual rates of 4.28 and 4.48. This reduction was evident across the spectrum of baseline blood eosinophil levels: REALITI-A, <150 n=96 (66%), ≥500 n=278 (75%) and REDES <150 n=25 (70%), ≥500-<700 n=61 (88%), ≥700 n=124 (81%). Conclusions: These real-world studies identify that mepolizumab, as used by physicians, is effective in standard clinical care irrespective of type 2 eosinophil biomarker status (high or low) in patients with severe asthma.