Abstract
BackgroundWe assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI).MethodsThis was a post hoc individual patient-level meta-analysis of data from the Phase 3 studies MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318). Patients aged ≥12 years with severe eosinophilic asthma and a history of exacerbations were randomised to 4-weekly placebo, mepolizumab 75 mg intravenously (IV) or 100 mg SC (MENSA) or placebo or mepolizumab 100 mg SC (MUSCA) for 32 (MENSA) or 24 (MUSCA) weeks. The primary endpoint was the annual rate of clinically significant exacerbations; other outcomes included the proportion of patients with no exacerbations, lung function, St George’s Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores and blood eosinophil counts. Analyses were performed by baseline body weight and BMI (≤60, > 60–75, > 75–90, > 90, < 100, ≥100 kg; ≤25, > 25–30, > 30, < 36, ≥36 kg/m2).ResultsOverall, 936 patients received placebo or mepolizumab 100 mg SC. Across all body weight/BMI categories, mepolizumab reduced the rate of clinically significant exacerbations by 49–70% versus placebo. Improvements with mepolizumab versus placebo were also seen in lung function in all body weight/BMI categories except > 90 kg; improvements in SGRQ and ACQ-5 scores were seen across all categories.ConclusionsMepolizumab 100 mg SC has consistent clinical benefits in patients with severe eosinophilic asthma across a range of body weights and BMIs. Data show that the fixed-dose regimen of mepolizumab is suitable, without the need for weight-based dosing.Trial registrationThis manuscript is a post hoc meta-analysis of data from the Phase 3 studies MENSA and MUSCA. ClinicalTrials.gov, NCT01691521 (MEA115588; MENSA). Registered September 24, 2012. ClinicalTrials.gov, NCT02281318 (200862; MUSCA). Registered November 3, 2014.
Highlights
We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI)
It is important to explore the treatment response of fixed-dosed regimens across a wide spectrum of body compositions. The aim of this post hoc meta-analysis of data from two Phase 3 clinical trials, MENSA (MEA115588/NCT01691521) and MUSCA (200862/NCT02281318) [7, 8], was to assess the efficacy of the licensed dose of mepolizumab (100 mg SC) versus placebo in patients with severe eosinophilic asthma according to body weight and body mass index (BMI)
A post hoc pooled analysis of the Phase 3 SIROCCO and CALIMA trials demonstrated that the effects of the anti-IL-5 receptor monoclonal antibody (mAb) benralizumab on the annual rate of exacerbations and lung function in patients with severe eosinophilic asthma were less robust in obese individuals than in those who were of normal weight [16]
Summary
We assessed the efficacy of the licensed mepolizumab dose (100 mg subcutaneously [SC]) in patients with severe eosinophilic asthma according to body weight/body mass index (BMI). Patients with severe eosinophilic asthma often develop disease in adult life, experience recurrent exacerbations and characteristically show eosinophilic inflammation despite appropriate treatment [2, 3], highlighting a need for more targeted therapy. In Phase 3 clinical studies, mepolizumab treatment was associated with reduced rates of exacerbations, decreased oral glucocorticoid dependence and improved lung function, asthma control and health-related quality of life (HRQoL), compared with placebo [6,7,8]. Mepolizumab is approved in the US and Europe for use as an add-on treatment for patients with severe eosinophilic asthma, and the licensed dose for adults and adolescents, administered subcutaneously (SC), is fixed at 100 mg, regardless of body weight [4, 5]. It is important to explore the treatment response of fixed-dosed regimens across a wide spectrum of body compositions
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