Mepolizumab was associated with clinical improvements among patients with severe eosinophilic asthma, across a range of body mass index (BMI) and body weight categories, according to a post hoc analysis published in Respiratory Research.
Researchers conducted a post hoc individual patient-level meta-analysis of data from 2 placebo-controlled, randomized, double-blind, parallel-group, multicenter phase 3 clinical trials (MENSA; ClinicalTrials.gov Identifier: NCT01691521 and MUSCA; ClinicalTrials.gov Identifier: NCT02281318).
In the MENSA trial, participants were randomly assigned to receive 75 mg mepolizumab via intravenous administration, 100 mg mepolizumab via subcutaneous administration, or placebo for 32 weeks every 4 weeks. Meanwhile, in the MUSCA trial, participants were randomly assigned to receive either 100 mg mepolizumab via subcutaneous administration or placebo plus standard care for 24 weeks every 4 weeks. However, this post hoc analysis only reports on data from patients who received the 100 mg subcutaneous dose or placebo in patients ≥12 years of age with severe eosinophilic asthma (defined as a blood eosinophil count of ≥300 cells/µL in the prior year or 150 cells/µL at screening), based on BMI and body weight.
The primary study end point was the annual rate of clinically significant exacerbations (defined as the worsening of asthma that necessitated the use of systemic corticosteroids and/or hospitalization or an emergency department visit). Secondary end points included the proportion of patients with no clinically significant exacerbations during the study, lung function as measured by forced expiratory volume in 1 second, changes in St. George’s Respiratory Questionnaire (SGRQ) and Asthma Control Questionnaire-5 (ACQ-5) scores, and blood eosinophil counts. All analyses were performed according to baseline body weight (categories for all end points: ≤60 kg, >60-75 kg, >75-90 kg, and >90 kg; thresholds for primary end point only: <100 kg and ≥100 kg) and BMI values (categories for all end points: ≤25 kg/m2, >25-30 kg/m2, and >30 kg/m2; thresholds for primary end point only: <36 kg/m2 and ≥36 kg/m2).
A total of 936 patients received either mepolizumab 100 mg subcutaneously or placebo. Across all body weights and BMI categories, treatment with mepolizumab decreased the rate of clinically significant disease exacerbations by 49% to 70% vs placebo. Moreover improvements in lung function were also reported with mepolizumab vs placebo in all body weight/BMI categories except >90 kg. There were also improvements in SGRQ and ACQ-5 scores observed across all categories.
The investigators concluded that mepolizumab 100 mg administered subcutaneously demonstrated consistent clinical benefits in patients with severe eosinophilic asthma across a broad range of BMIs and body weights. The fixed-dose regimen of mepolizumab is appropriate, with no need for weight-based dosing. However, the researchers pointed out that “[t]he reason for the lower improvement in FEV1 in the highest body weight category remains to be investigated.”
Albers FC, Papi A, Taillé C, et al. Mepolizumab reduces exacerbations in patients with severe eosinophilic asthma, irrespective of body weight/body mass index: meta-analysis of MENSA and MUSCA [published online July 30, 2019].Respir Res. doi:10.1186/s12931-019-1134-7