Association Between T2-related Comorbidities and Effectiveness of Biologics in Severe Asthma

Abstract

<b>Rationale:</b> Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents. <b>Objectives:</b> To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA). <b>Methods:</b> This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV₁% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis. <b>Measurements and Main Results:</b> Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%; <i>P</i> < 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%; <i>P</i> < 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV₁% predicted improvement of 3.2% (95% CI, 1.0-5.3; <i>P</i> = 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed. <b>Conclusions:</b> These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.