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

Abstract

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 ≥ 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 (FEV1), 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; ≥ 40 years); lung function (% predicted FEV1 ≤ 60; 60-80; > 80); airway reversibility (reversible [≥ 12% change in FEV1]; non-reversible [< 12% change in FEV1]); perennial and/or seasonal allergen sensitivity (yes/no); asthma control (uncontrolled [ACQ-5 score ≥ 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-world studies are needed to confirm the external validity of these findings. Trial registration Post hoc meta-analysis of data from MENSA (NCT01691521/MEA115588) and MUSCA (NCT02281318/200862).

Keywords: Airway reversibility; Allergen sensitivity; Asthma; Asthma control; Exacerbations; Health-related quality of life; Lung function; Mepolizumab.

Conflict of interest statement

CL has received personal fees for consultancy services and participation in clinical research projects (as an investigator) with GSK, AstraZeneca, Novartis, Sanofi and Teva Innovation; research grants from GSK and Sanofi. CT has received personal fees for consultancy services, speaking at conferences, and participation in clinical research projects (as an investigator) with GSK, AstraZeneca, Novartis, Roche, Sanofi, Chiesi and Teva. JKL reports grants and personal fees from Novartis, AstraZeneca and Sanofi, as well as personal fees from GSK, Merck and CSL. FCA is an employee of Avillion US, Inc. and a former employee of GSK with stock/stock options in GSK. ESB is a former employee of GSK and is currently employed by Aeglea BioTherapeutics, Austin, TX, USA; he has stocks/shares in both companies. MCL reports personal fees for advisory board attendance from GSK, Gossamer Bio and AstraZeneca; research grants from GSK and Gossamer Bio. SGS, SM and SWY are current employees of GSK, and hold stocks/shares in GSK.

Figures

Fig. 1

Efficacy of mepolizumab, by age at asthma onset, lung function, and airway reversibility. A Annualised rates of clinically significant exacerbations; B Change from baseline to study end in pre-bronchodilator FEV1; C Change from baseline to study end in SGRQ total score; D Change from baseline to study end in ACQ-5 score. All plots are for patients receiving mepolizumab versus placebo. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1 sm ITT intent-to-treat, SGRQ St George’s Respiratory Questionnaire

Fig. 2

Annualised clinically significant exacerbation rates with mepolizumab versus placebo, by allergen sensitivity. A Annualised rate of exacerbations per season, for patients with and without allergen sensitivities receiving mepolizumab and placebo; B Rate ratio (mepolizumab versus placebo) of annualised exacerbation rates per season, for patients with and without allergen sensitivities; C Annualised rate of exacerbations per season, for patients with and without seasonal allergen sensitivities receiving mepolizumab and placebo; D Rate ratio (mepolizumab vs placebo) of annualised exacerbation rates per season, for patients with and without seasonal allergen sensitivities. For all radial plots, each increment of the radial axis represents 0.1 exacerbations/year, with the outer ring representing a possible maximum of 2.5 exacerbations/year. CI confidence interval

Fig. 3

Efficacy of mepolizumab, by allergen sensitivity. A Change from baseline to study end in pre-bronchodilator FEV1 per season; B Change from baseline to study end in SGRQ total score per season; C Change from baseline to study end in ACQ-5 score per season. All plots are for patients receiving mepolizumab versus placebo. ACQ Asthma Control Questionnaire, CI confidence interval, FEV1 forced expiratory volume in 1 s, SGRQ St George’s Respiratory Questionnaire

Fig. 4

Proportion of patients achieving complete asthma control with mepolizumab versus placebo. Complete asthma control was defined as an ACQ-5 score †defined as an ACQ-5 score < 1.5. ACQ Asthma Control Questionnaire, CI confidence interval