Mepolizumab real-world effectiveness in severe asthma with an eosinophilic phenotype and overlapping severe allergic asthma

Background: Some patients with severe asthma have overlapping allergic and eosinophilic phenotypes and may be eligible for anti-eosinophilic or anti-immunoglobin E (IgE) biologics. Objective: This post hoc sub-analysis assessed real-world mepolizumab effectiveness in patients with overlapping allergic and eosinophilic phenotypes, using 1-year data from the international, prospective REALITI-A (REAL world effectiveness of mepolizumab In paTIent care – Asthma) study. Methods: The clinically significant asthma exacerbations (CSE) rate was assessed 1 year before (pretreatment) and after (follow-up) mepolizumab treatment, stratified by baseline total IgE (tIgE) levels (<60, 60 to <190, 190 to <550, and ≥550 kilounits per litre [kU/L]), atopic status (yes/no/unknown), previous omalizumab use (yes/no), geographic baseline omalizumab eligibility (eligible/non-eligible), and baseline tIgE level and blood eosinophil count threshold combinations (<81 or ≥81 kU/L and <300 or ≥300 cells per microliter [cells/μL]). Results: Overall, 822 patients were included. CSEs occurred in 760 patients (93%) pretreatment and 398 patients (49%) during follow-up. CSE rate (rate ratio [95% CI]) was reduced in follow-up across all tIgE subgroups (<60 [n = 173]: 0.31 [0.25-0.37]; 60 to <190 [n = 176]: 0.30 [0.25-0.36]; 190 to <550 [n = 170]: 0.26 [0.20-0.33]; ≥550 kU/L [n = 155]: 0.28 [0.23-0.35]) and irrespective of atopic status (yes [n = 422]: 0.29 [0.26-0.33]; no [n = 52]: 0.33 [0.23-0.47]; unknown [n = 348]: 0.28 [0.24-0.32]), previous omalizumab use (yes [n = 151]: 0.37 [0.30-0.45]; no [n = 671]: 0.27 [0.24-0.30]), or eligibility (eligible [n = 349]: 0.29 [0.25-0.34]; non-eligible [n = 191]: 0.32 [0.27-0.38]). Furthermore, the CSE rate was reduced across all tIgE (kU/L) and blood eosinophil count (cells/μL) combinations (<81/<300 [n = 53]: 0.34 [0.24-0.47]; <81/≥300 [n = 103]: 0.33 [0.26-0.41]; ≥81/<300 [n = 98]: 0.36 [0.28-0.47]; ≥81/≥300 [n = 249]: 0.26 [0.22-0.31]). Conclusion: Mepolizumab demonstrates real-world effectiveness in reducing exacerbations in patients with severe asthma and an eosinophilic phenotype, regardless of any overlapping allergic phenotype.