Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials

• Published in: Respiratory research 2021-06, Vol.22 (1), p.1-184, Article 184
• Main Authors: Lemiere, Catherine, Taillé, Camille, Lee, Jason Kihyuk, Smith, Steven G, Mallett, Stephen, Albers, Frank C, Bradford, Eric S, Yancey, Steven W, Liu, Mark C
• Format: Article
• Language: English
• Subjects: Age; Airway reversibility; Allergen sensitivity; Allergens; Allergies; Asthma; Asthma control; Bronchodilators; Clinical medicine; Clinical trials; Data analysis; Drug therapy; Leukocytes (eosinophilic); Lung function; Lungs; Mepolizumab; Meta-analysis; Monoclonal antibodies; Patients; Phenotypes; Placebos; Questionnaires; Respiratory function; Respiratory tract; Sensitivity; Subgroups
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-021-01767-z

Background Severe asthma is associated with a broad range of phenotypes and clinical characteristics. This analysis assessed whether select baseline patient characteristics could prognosticate mepolizumab efficacy in severe eosinophilic asthma. Methods This was a post hoc meta-analysis of data from the Phase III MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862) studies. Patients aged [greater than or equai to] 12 years with severe eosinophilic asthma and a history of exacerbations were randomised to receive placebo (MENSA/MUSCA), mepolizumab 75 mg intravenously (MENSA) or 100 mg subcutaneously (SC) (MENSA/MUSCA) every 4 weeks 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 and changes from baseline in pre-bronchodilator forced expiratory volume in 1 s (FEV.sub.1), St George's Respiratory Questionnaire (SGRQ) total score and Asthma Control Questionnaire (ACQ)-5 score. Analyses were performed by baseline age of asthma onset (< 18 years; 18-40 years; [greater than or equai to] 40 years); lung function (% predicted FEV.sub.1 [less than or equai to] 60; 60-80; > 80); airway reversibility (reversible [[greater than or equai to] 12% change in FEV.sub.1]; non-reversible [< 12% change in FEV.sub.1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score [greater than or equai to] 1.5]; partial/complete control [ACQ-5 score < 1.5]). Results Overall, 936 patients received mepolizumab 100 mg SC or placebo. Across age at asthma onset, lung function and airway reversibility subgroups, mepolizumab reduced the rate of clinically significant exacerbations by 49-63% versus placebo. Improvements in lung function, SGRQ total score and ACQ-5 score were also seen with mepolizumab versus placebo across most age and lung function subgroups. Clinically significant exacerbations were reduced with mepolizumab versus placebo irrespective of season or allergen sensitivity; SGRQ total and ACQ-5 scores were generally improved across seasons. Conclusions Mepolizumab efficacy was consistent for patients with varying age at asthma onset, lung function, airway reversibility and allergen sensitivities at baseline. Our results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma with a broad range of baseline clinical characteristics; large-scale real-w