Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions

Abstract

Background: Comorbidities can complicate the management of severe asthma; therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities.

Methods: This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM); mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA); or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations; secondary endpoints were Asthma Control Questionnaire-5 score, St George's Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline.

Results: Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44-68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27-0.59 points, and improved St George's Respiratory Questionnaire total score by 5.0-11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1-286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup.

Conclusions: Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity.

Trial registration: https://clinicaltrials.gov/ DREAM, MEA112997/NCT01000506; MENSA, MEA115588/NCT01691521; SIRIUS, MEA115575/NCT01842607; MUSCA, 200862/NCT02281318.

Keywords: Cardiovascular; Comorbidities; Mepolizumab; Severe eosinophilic asthma; Treatable traits; Upper respiratory.

Fig. 1

Rate of clinically significant exacerbations by comorbidity category. The rate of clinically significant exacerbations was analyzed using a negative binomial generalized linear model with a log-link function, including log of time on treatment as an offset variable. p-interaction < 0.1. AR allergic rhinitis/hay fever; CI confidence interval; GERD gastroesophageal reflux disease; mepo mepolizumab

Fig. 2

Change from baseline in ACQ-5 score at Week 24 by comorbidity category. Change from baseline in ACQ-5 score was analyzed using a MMRM analysis. The currently accepted minimum clinically important difference for ACQ-5 score is 0.5 points (established in adults with symptomatic asthma) [38]. p-interaction < 0.1. ACQ, Asthma Control Questionnaire; AR allergic rhinitis/hay fever; CI confidence interval; GERD gastroesophageal reflux disease; mepo mepolizumab; MMRM mixed model repeated measures

Fig. 3

Change from baseline in SGRQ total score at Week 24 by comorbidity category. Change from baseline in SGRQ total score was analyzed using analysis of covariance. The currently accepted minimum clinically important difference for SGRQ is 4 units (established in an average population of patients with chronic obstructive pulmonary disease) [25]. p-interaction < 0.1. AR allergic rhinitis/hay fever; CI confidence interval; GERD gastroesophageal reflux disease; mepo mepolizumab; SGRQ St George’s Respiratory Questionnaire

Fig. 4

Change from baseline in pre-bronchodilator FEV₁ (mL) at Week 24 by comorbidity category. Change from baseline in pre-bronchodilator FEV₁ was analyzed using a MMRM analysis. p-interaction < 0.1. AR allergic rhinitis/hay fever; CI confidence interval; FEV₁ forced expiratory volume in 1 s; GERD gastroesophageal reflux disease; mepo mepolizumab; MMRM mixed model repeated measures