Background: Although there have been indirect comparisons of the relative efficacy of mepolizumab (anti-IL-5) and benralizumab (anti-IL-5Rα) in severe asthma patients, long-term direct head-to-head comparisons are lacking. Here, we (i) examined the effect of mepolizumab, benralizumab, and omalizumab on symptom control and lung function parameters over time; and (ii) compared the efficacy of mepolizumab and benralizumab on symptom control and lung function outcomes. Methods: This was a retrospective study of patients with severe asthma taking anti-IgE (omalizumab; n = 24), anti-IL5 (mepolizumab, n = 23), or anti-IL-Rα (benralizumab; n = 12) therapy. Data were extracted on (i) Asthma Control Questionnaire (ACQ-5) scores; (ii) forced expiratory volume over 1 second (FEV 1 ); and (iii) peak expiratory flow rate (PEFR) at 4-6 months and 1 year and documented reductions in exacerbations. Clinical and lung function outcomes were compared between patients taking mepolizumab and benralizumab and over time. Results: There were significant decreases in ACQ-5 scores (3.3 ± 0.93 to 1.7 ± 0.98 for mepolizumab, 3.5 ± 0.72 to 1.6 ±0.89 for benralizumab, and 3.5 ± 0.95 to 1.7 ± 1.1 for omalizumab; t-test, all p < 0.0001) but not increases in FEV 1 and PEFR for all three agents after 4-6 months of therapy, which persisted but did not decrease further at one year. There were trends toward a greater percentage increase in FEV 1 and PEFR from baseline and a decrease in the number of exacerbations in patients taking benralizumab than those taking mepolizumab. Conclusion:Although limited by a small sample size, this real-world, head-to-head comparison of mepolizumab and benralizumab is consistent with comparative data on asthma biologicals and indirect comparisons showing no major difference in efficacy. The study also generates new testable hypotheses about the efficacy of asthma biologicals in different patient populations.

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BackgroundMultidisciplinary systematic assessment improves outcomes in difficult‐to‐treat asthma, but without clear response predictors. Using a treatable‐traits framework, we stratified patients by trait profile, examining clinical impact and treatment responsiveness to systematic assessment.MethodsWe performed latent class analysis using 12 traits on difficult‐to‐treat asthma patients undergoing systematic assessment at our institution. We examined Asthma Control Questionnaire (ACQ‐6) and Asthma Quality of Life Questionnaire (AQLQ) scores, FEV1, exacerbation frequency, and maintenance oral corticosteroid (mOCS) dose, at baseline and following systematic assessment.ResultsAmong 241 patients, two airway‐centric profiles were characterized by early‐onset with allergic rhinitis (n = 46) and adult onset with eosinophilia/chronic rhinosinusitis (n = 60), respectively, with minimal comorbid or psychosocial traits; three non‐airway‐centric profiles exhibited either comorbid (obesity, vocal cord dysfunction, dysfunctional breathing) dominance (n = 51), psychosocial (anxiety, depression, smoking, unemployment) dominance (n = 72), or multi‐domain impairment (n = 12). Compared to airway‐centric profiles, non‐airway‐centric profiles had worse baseline ACQ‐6 (2.7 vs. 2.2, p < .001) and AQLQ (3.8 vs. 4.5, p < .001) scores. Following systematic assessment, the cohort showed overall improvements across all outcomes. However, airway‐centric profiles had more FEV1 improvement (5.6% vs. 2.2% predicted, p < .05) while non‐airway‐centric profiles trended to greater exacerbation reduction (1.7 vs. 1.0, p = .07); mOCS dose reduction was similar (3.1 mg vs. 3.5 mg, p = .782).ConclusionDistinct trait profiles in difficult‐to‐treat asthma are associated with different clinical outcomes and treatment responsiveness to systematic assessment. These findings yield clinical and mechanistic insights into difficult‐to‐treat asthma, offer a conceptual framework to address disease heterogeneity, and highlight areas responsive to targeted intervention.