Population-Level Trends in Asthma Exacerbations After Introduction of Respiratory Biologics.

Importance: Respiratory biologics have transformed the treatment for asthma, a disease affecting approximately 300 million individuals globally. Objective: To evaluate population-level trends in asthma exacerbations, including during a period encompassing approval of multiple biologics. Design, Setting, and Participants: This cohort study used electronic health records from a large health care system in Boston, Massachusetts, including specialty allergy and pulmonology clinics, from January 2006 to May 2025. Adults aged 18 years or older with physician-diagnosed asthma seen in specialty clinics were included. Patients with other chronic lung diseases, except chronic obstructive pulmonary disease, were excluded. Exposure: The year 2015 was designated a priori as the exposure change point to assess changes in asthma exacerbations, given that it marked the beginning of a period of rapid approval of respiratory biologics with 4 of the 6 respiratory biologics approved between 2015 and 2018. Main Outcomes and Measures: The primary outcomes were the changes in the intercept and slope of annual exacerbations per 1000 asthma patients per year. Immediate and sustained reductions in exacerbations were evaluated using the interrupted time series analytic approach. Subgroup analyses evaluated changes by severity, baseline eosinophil count, and demographic or clinical characteristics. Results: Among 5269 adults with asthma (mean [SD] age, 51.9 [18.3] years; 3761 female [71.4%]), exacerbations increased from 2006 to 2015 (155.4 [95% CI, 117.7 to 193. 2] events per 1000 patients per year). After 2015, an immediate reduction occurred (-474.1 [95% CI, -783.2 to -165.0] events per 1000 patients per year), followed by a sustained yearly decline (-206.5 [95% CI, -259.9 to -153.0] events per 1000 patients per year). Patients with 2 or more annual exacerbations showed greater improvements (immediate: -808.2 [95% CI, -1646.5 to 30.2] events per 1000 patients per year; slope: -374.5 [95% CI, -519.4 to -229.7] events per 1000 patients per year) than patients with fewer than 2 exacerbations. Those with baseline eosinophil levels of 450 cells/μL or greater exhibited significant declines (immediate: -1799.8 [95% CI, -3555.3 to -44.3] events per 1000 patients per year; slope: -443.4 [95% CI, -746.7 to -140.0] events per 1000 patients per year) compared with patients with eosinophil levels less than150 cells/μL. Reductions occurred across age, sex, body mass index, smoking, and insurance subgroups, although smokers and inner-city residents retained higher absolute rates. Conclusions and Relevance: In this cohort study of 5269 adults with asthma, there were significant reductions in asthma exacerbations, particularly among patients with severe or eosinophilic disease. Importantly, these benefits closed the outcome gap between patients with moderate to severe asthma and those with mild asthma, and support the effectiveness of biologics, highlighting their potential to improve outcomes among high-risk populations.