Mepolizumab benefits patients with severe asthma across the board

The interleukin-5 (IL-5) inhibitor mepolizumab reduces asthma exacerbations in patients with severe asthma across a broad range of baseline clinical characteristics and regardless of comorbidities, according to studies presented at the 2021 AAAAI Meeting.

While add-on mepolizumab has previously been shown to reduce exacerbations and approved for treating severe asthma with an eosinophilic phenotype, whether select baseline clinical features can influence the efficacy of mepolizumab is not yet known.

In a post hoc meta-analysis of the phase III, double-blind, global MENSA and MUSCA studies, researchers stratified data of 936 patients with severe eosinophilic asthma (SEA) by characteristics such as age of asthma onset, asthma control, lung function, and airway reversibility at baseline. They were randomized to receive either subcutaneous mepolizumab 100 mg or placebo every 4 weeks, for 32 weeks in MENSA and 24 weeks in MUSCA. [AAAAI 2021, abstract 174]

Mepolizumab led to 49–63 percent reductions in the primary endpoint of clinically significant exacerbations* compared with placebo, regardless of age at asthma onset, lung function as indicated by FEV1, and airway reversibility at baseline (hazard ratios [HRs], 0.37 to 0.51).  

Similarly, improvement in lung function measured by FEV₁ was seen with mepolizumab vs placebo across all age at asthma onset and baseline lung function subgroups (change in FEV₁, 77–127 mL).

In addition, consistent improvement in asthma control was also seen across all age at asthma onset and lung function subgroups, as reflected in better ACQ-5** score in the mepolizumab group vs the placebo group (treatment difference, -0.48 to -0.27 for age at asthma onset; -0.46 to -0.39 for lung function at baseline); as was for health-related quality of life measured using SGRQ*** (treatment difference, -9.4 to -3.3 for age at asthma onset; -9.0 to -7.1 for lung function at baseline).

“These results indicate that mepolizumab is likely to be beneficial for patients with severe eosinophilic asthma who have a broad range of baseline characteristics,” the researchers concluded.

A separate real-world study looked at the efficacy of mepolizumab in asthma patients with atopy, obesity, or depression/anxiety — comorbidities which have become increasingly common among patients with asthma.

The retrospective analysis involved patients with severe asthma (mean age ~51 years) in the US healthcare claim database, who initiated mepolizumab treatment. [AAAAI 2021, abstract 173]     

After 12 months of follow-up, patients experienced significantly fewer exacerbations overall after starting on mepolizumab compared with baseline, regardless of whether they had pre-existing atopy (change, -48 percent; p<0.001), obesity (change, -52 percent; p<0.001), or depression/anxiety (change, -38 percent; p<0.001).

The rate of asthma exacerbations requiring hospitalizations was reduced by 64 percent in patients with atopy, 65 percent in those with obesity, and 68 percent in those with depression/anxiety (p<0.001 for all) 12 months after initiating mepolizumab compared with baseline.

Similarly, mepolizumab also led to a reduced need for oral corticosteroids (OCS), as indicated by number of OCS claims, during the 12 months of follow-up across patients with atopy (change, -33 percent), obesity (change, -38 percent), or depression/anxiety (change, -31 percent; p<0.001 for all).

“This study demonstrates that patients with asthma and atopy, obesity or depression/anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting following treatment with mepolizumab,” the researchers reported.

“Holistic patient care for severe asthma is critical and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities,” they stated.

*Requiring administration of systemic glucocorticoids for ≥3 days or an emergency department visit/hospitalization

**ACQ-5: Asthma Control Questionnaire-5
***SGRQ: St. George’s Respiratory Questionnaire