Mepolizumab Improves Clinical Outcomes in Severe Asthma With Comorbidities

asthma, lungs
asthma, lungs
In patients with severe eosinophilic asthma and comorbidities, treatment with mepolizumab is associated with improvements in exacerbate rate and lung function.

In patients with severe eosinophilic asthma and self-reported comorbid upper airway disease or other comorbidities, treatment with mepolizumab is associated with improvements in exacerbation rate, asthma control, lung function, and health-related quality of life, according to study results published in Respiratory Research.  

Researchers conducted a post hoc meta-analysis (GSK ID: 209140) of data from 4 separate phase 2B/3 clinical trials—DREAM ( Identifier: NCT01000506), MENSA ( Identifier: NCT01691521), SIRIUS ( Identifier: NCT01691508), and MUSCA ( Identifier: NCT02281318). They sought to explore the efficacy of mepolizumab in patients with severe asthma and comorbidities. The 4 trials included patients aged 12 years and older who had severe eosinophilic asthma, defined as a blood eosinophilic count of ≥150 cells/µL at baseline or ≥300 cells cells/µL in the prior year.

The primary study endpoint was the annual rate of clinically significant exacerbations, which was defined as a worsening of asthma that required the use of systemic corticosteroids and/or hospitalization or emergency department visits. Secondary endpoints included changes from baseline in prebronchodilator forced expiratory volume in 1 second (FEV1), St. George’s Respiratory Questionnaire (SGRQ) total score, and Asthma Control Questionnaire (ACQ)-5 score at the conclusion of the study.

Patient subgroups were based on the self-reported presence of current medical conditions at the screening visit for each of the studies. Comorbid condition subgroups included upper respiratory, psychopathologies, cardiovascular, gastroesophageal reflux disease, diabetes, and obesity.

Patients were randomly assigned  to mepolizumab 750 mg, 250 mg, or 75 mg intravenously (IV) or placebo (DREAM); mepolizumab 75 mg IV, 100 mg subcutaneously (SC), or placebo (MENSA); or mepolizumab 100 mg SC or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA, and 52 weeks in DREAM.

Among a total of 1878 participants, 1189 received at least 1 dose of mepolizumab and 689 received at least 1 dose of placebo during the DREAM, MENSA, SIRIUS, and MUSCA trials. The baseline demographics were similar between the trials, with the exception of oral corticosteroid (OCS) use in SIRIUS, with all participants in that study required to have been receiving OCSs at baseline.

Results of the study showed that across all comorbidity subgroups, mepolizumab therapy reduced the rate of clinically significant disease exacerbations by 44% to 68% vs placebo treatment, improved the ACQ-5 score by 0.27 to 0.59 points, and improved the SGRQ total score by 5.0 to 11.6 points. Further, prebronchodilator FEV1 was improved by 27.1 to 286.9 mL in all but the diabetes subgroup.

The investigators concluded that the findings from this meta-analysis imply that mepolizumab is clinically beneficial for providing targeted treatment and helping to reduce disease burden among patients with severe eosinophilic asthma and comorbidities.

Disclosure: This research was supported by GlaxoSmithKline. Please see the original reference for a full list of authors’ disclosures. 


Gibson PG, Prazma CM, Chupp GL, et al. Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions. Respir Res. 2021;22(1):171. doi:10.1186/s12931-021-01746-4