Biological Therapy Persistence in Severe Asthma: Real-World Evidence Beyond Fixed Follow-Up Analysis

<title>Abstract</title> <p>Long-term durability of biological therapy in severe asthma remains insufficiently characterized in real-world clinical practice. Most currently available studies assess treatment effectiveness at predefined follow-up points, potentially overlooking patients who discontinue therapy earlier due to secondary loss of response or insufficient disease control. We performed a retrospective real-world cohort study including 529 patients with severe asthma treated with omalizumab, mepolizumab, or benralizumab to evaluate long-term biologic treatment persistence, defined as time to loss of clinically effective therapy, using a survival-based time-to-relapse model and to identify baseline predictors of long-term treatment persistence. Time-to-relapse was defined as loss of clinically meaningful treatment effectiveness resulting in biologic discontinuation or switching. Patients treated with omalizumab presented lower eosinophilia and earlier disease onset, whereas anti-IL-5/IL-5R therapies were associated with a more pronounced eosinophilic phenotype and greater corticosteroid burden. Among 81 observed relapses, 61.7% occurred between scheduled follow-up visits. The 90th percentile of time-to-relapse was 48 months for mepolizumab, compared with 20 months for benralizumab and 11 months for omalizumab (p = 0.003). In multivariate analysis, baseline ACQ, FEV1, and peripheral blood eosinophilia emerged as independent predictors of biologic treatment persistence. Biologic treatment persistence may represent a clinically meaningful long-term outcome measure and support the broader application of survival-based methodologies in future real-world studies of severe asthma. Maintenance of biologic therapy in severe asthma could constitute a significant factor for therapy choice; in this context time-to-relapse may provide a more realistic information than results from conventional fixed follow-up models, biased by patients “vanishing” between check-points.</p>