Effectiveness of Mepolizumab in Patients Switching From Prior Biologic Treatments for Severe Asthma: A Post-hoc Analysis of NUCALA Effectiveness Study (NEST)

Abstract RATIONALE: Biologic treatment is recommended as add-on treatment for severe asthma management to reduce exacerbations. Mepolizumab is a first-in-class targeted anti-interleukin-5 (anti-IL5) monoclonal antibody used to treat type 2 inflammatory diseases including severe asthma with an eosinophilic phenotype. Mepolizumab is widely accessible in the Middle East, Asia, and Latin America, however, disease-related burden remains high in these countries. The NUCALA Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma. METHODS: This was a post-hoc analysis of patients who switched from a previous biologic to mepolizumab for the treatment of severe asthma in NEST. NEST was a bi-directional, self-controlled, observational study of adults with severe asthma who received ≥1 dose mepolizumab 100 mg; data were collected 12 months pre- and up to 12 months post-initiation. The study population included patients from Türkiye, Colombia, India, Chile, Saudi Arabia, Kuwait, Oman, Qatar, and the United Arab Emirates. The primary endpoint was rate of clinically significant exacerbations (CSEs, defined as asthma exacerbation that required systemic corticosteroids [oral corticosteroids (OCS) for ≥3 days or a single dose of intravenous/intramuscular corticosteroid] and/or an emergency room visit and/or hospitalization). Other endpoints included level of asthma control (Asthma Control Test [ACT]) and OCS use. RESULTS: Patients with severe asthma who switched from a previous biologic to mepolizumab constituted 33.1% (n=174) of the NEST population. Pre-initiation, the mean number of CSEs was 1.56 (95% confidence interval [CI] 1.27-1.93); mean (standard deviation [SD]) ACT score was 13.94 (5.39); mean (SD) OCS dose was 20.81 (17.29) mg/day and the geometric mean blood eosinophil count was 446.4 cells/µL. Biologics used pre-initiation included omalizumab (94.8%), dupilumab (0.2%), and other anti-IL5 biologics (4.0%). Post-initiation, the mean number of CSEs was 0.47 (95% CI 0.35-0.63). Mepolizumab treatment was associated with a significant reduction in CSEs (74% reduction; incident rate ratio [95% CI] 0.26 [0.18-0.36]; Table). The proportion of patients who achieved asthma control (ACT score of ≥20) increased from pre- to post-initiation (19.4% vs. 64.3%). Post-initiation, the mean (SD) dose of OCS was 6.73 (15.26) mg/day; mean (SD) difference in OCS dose from pre- to post-initiation was 14.08 (17.00) mg/day. Overall, 61.8% of patients became OCS-free post-initiation. CONCLUSIONS: This post-hoc analysis demonstrated the effectiveness of mepolizumab in reducing CSEs and OCS use by inhibition of IL-5 in patients with severe asthma who had previously received other biologic therapies, mostly omalizumab, in the countries studied.