Effect of mepolizumab in severe eosinophilic asthma according to omalizumab eligibility

Abstract

Background: Patients with severe asthma can present with overlapping eosinophilic and allergic phenotypes, which makes it challenging when deciding which biologic therapy is most appropriate to reduce exacerbations and help achieve asthma control. Objective: This post hoc meta-analysis evaluated the efficacy of the licensed dose of mepolizumab (100 mg administered subcutaneously [SC]) versus placebo in patients with severe eosinophilic asthma (SEA), according to omalizumab eligibility and associated allergic characteristics. Methods: Data from two Phase 3 studies (MENSA [MEA115588/NCT01691521]; MUSCA [200862/ NCT02281318]) were analyzed. Patients ≥12 years of age with SEA who experienced ≥2 exacerbations in the previous year received placebo, mepolizumab 100 mg SC or 75 mg intravenously, plus standard of care (highdose inhaled corticosteroids and other controllers), every 4 weeks. Data from patients who received ≥1 dose placebo or mepolizumab 100 mg SC were used for this analysis. The primary endpoint was the rate of clinically significant exacerbations; other outcomes included forced expiratory volume in 1 s (FEV 1 ), Asthma Control Questionnaire (ACQ-5) score and quality of life measured using St George's Respiratory Questionnaire (SGRQ). Results: Rate reductions in clinically significant exacerbations with mepolizumab versus placebo were similar in omalizumab eligible and ineligible patients (57% vs 55%). FEV 1 , ACQ-5 and SGRQ scores improved with mepolizumab versus placebo regardless of omalizumab eligibility, Immunoglobulin E levels, or atopic status. Conclusion: This analysis indicated that mepolizumab 100 mg SC has clinical benefit in patients with blood eosinophil counts ≥150 cells/μL (or history of ≥300 cells/μL), regardless of allergic characteristics or omalizumab eligibility.

Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma

“…Mepolizumab, a marketed human antiinterleukin-5 monoclonal antibody for patients with severe eosinophilic asthma [19], has been evaluated in two separate studies for patients who either received [20] or were qualified at study entry [21] to receive omalizumab treatment. In a post hoc analysis of the phase III MENSA trial [22], patients who received omalizumab had a 57% exacerbation rate reduction with mepolizumab vs. placebo (compared with 47% for those who did not receive omalizumab) [20].…”

“…In a post hoc analysis of the phase III MENSA trial [22], patients who received omalizumab had a 57% exacerbation rate reduction with mepolizumab vs. placebo (compared with 47% for those who did not receive omalizumab) [20]. In a post hoc meta-analysis of data from the phase III MENSA [22] and MUSCA [23] trials, mepolizumab reduced exacerbation rates vs. placebo by 57% and 55% for patients who were qualified or unqualified for omalizumab (based on prescribing and dosing criteria), respectively [21]. Together with our findings, this supports the use of agents that target eosinophils directly A limitation of this study was the small numbers of patients for the different subgroups, which restricted interpretation of the findings with no consistent trends.…”

EAACI Biologicals Guidelines—Recommendations for severe asthma

“…For the use of mepolizumab in allergic asthma in a licensed dose, an open multicentre, open‐label, single‐arm study showed clinically significant improvements in asthma control, health status and exacerbation rate 104 . The post hoc meta‐analysis of two phase 3 studies showed efficacy of mepolizumab regardless of allergic characteristics or omalizumab eligibility 105 . Recent reports show that both mepolizumab and reslizumab can control severe asthma patients that failed to respond to omalizumab 106 .…”

“…Dupilumab is recommended in adults and paediatric population 12-to 17-years old with uncontrolled severe T2 asthma* in spite of optimal controller treatment to: Dupilumab demonstrated a good safety profile; however, longer term data (up to 2 years) are extrapolated from atopic dermatitis studies and careful reporting of all drug-related adverse events is recommended For the use of mepolizumab in allergic asthma in a licensed dose, an open multicentre, open-label, single-arm study showed clinically significant improvements in asthma control, health status and exacerbation rate 104. The post hoc meta-analysis of two phase 3 studies showed efficacy of mepolizumab regardless of allergic characteristics or omalizumab eligibility 105. Recent reports show that both mepolizumab and reslizumab can control severe asthma patients that failed to respond to omalizumab 106.…”

Mepolizumab Effectiveness and Allergic Status in Real Life

“…However, both trials and real-life studies [5, 6] analyzed subjects with severe eosinophilic asthma regardless of allergic and nonallergic pathways leading to eosinophilic inflammation. Recently, post hoc meta-analysis and real-life studies have shown mepolizumab effectiveness in subjects affected by SAEA identified by using omalizumab eligibility or previous omalizumab treatment failure criteria [7, 8]. However, these studies compared eligible with ineligible omalizumab patients, although the latter may also include both individuals with seasonal allergies and high allergy-induced IgE levels.…”