Mepolizumab reduces exacerbations in overlapping eosinophilic, atopic severe asthma
The humanized monoclonal antibody mepolizumab reduces the rates of clinically significant exacerbations in patients with an overlapping eosinophilic and atopic severe asthma phenotype, regardless of serum IgE levels or whether they qualify for omalizumab, according to a meta-analysis of randomized trials presented in ATS 2018.
“As biologic therapies for severe asthma become the new standard of care, determining a patient’s asthma phenotype can aid clinical treatment decisions,” said the researchers led by Dr Mark Liu of Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, US.
“Mepolizumab (anti-interleukin-5) and omalizumab (anti-IgE) are monoclonal antibody therapies approved for severe eosinophilic asthma and moderate-severe allergic asthma, respectively,” they stated. “[Nonetheless,] in clinical practice, a subset of patients present with overlapping phenotypic characteristics making them eligible for both mepolizumab and omalizumab.”
In a post hoc meta-analysis of two phase III double-blind trials, MENSA* and MUSCA**, 936 patients with severe eosinophilic asthma were randomized 1:1 to receive subcutaneous injection of mepolizumab 100 mg Q4W or placebo, in addition to standard of care, for 32 weeks in MENSA and 24 weeks in MUSCA. [ATS 2018, abstract A7657]
Patients were categorized as “omalizumab-eligible” if their blood was positive for specific IgE for any of the five aeroallergens (dog dander, cat dander, house dust mite, cockroach, and Alternaria) and US-specific body weight (30–150 kg) vs pretreatment serum IgE (≥30–700 IU/mL) combinations.
Regardless of omalizumab eligibility, mepolizumab consistently reduced the annual rate of clinically significant exacerbations compared with placebo (rate ratios [RRs], 0.43 and 0.45 in omalizumab-eligible and -ineligible subgroups, respectively). Rates of severe exacerbations requiring hospitalization were also reduced with mepolizumab regardless of omalizumab eligibility (RRs, 0.32 and 0.42, respectively).
Consistent reductions in exacerbation rate were also seen across omalizumab IgE levels (RRs, 0.37 and 0.45 for IgE levels 30–350 IU/mL and IgE levels of >350–700 IU/mL, respectively).
When the analysis was stratified by blood eosinophil count (BEC), exacerbation reduction with mepolizumab was more pronounced in patients with BECs of ≥300 cells/μL than those with BECs <300 cells/μL (RRs, 0.32 vs 0.54, respectively).
“This post hoc meta-analysis of the MENSA and MUSCA clinical trials showed that treatment with the approved dose of mepolizumab (100 mg), plus standard of care, consistently reduced the annual rate of exacerbations in patients with an overlapping eosinophilic and atopic severe asthma phenotype, independent of omalizumab eligibility or omalizumab-qualifying IgE levels,” said Liu and co-authors.
“The data also support the well-characterized relationship between increasing BECs and mepolizumab treatment response,” they added.
“This analysis provides important information to aid clinical treatment decisions for patients with an overlapping phenotype who are eligible for both omalizumab and mepolizumab.”