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

To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma.This study included 1,765 patients ≥ 18 years in the International Severe Asthma Registry (ISAR) who had severe asthma and type 2-related comorbidities, including allergic rhinitis (AR), nasal polyposis (NP), chronic rhinosinusitis (CRS) with or without NP, and/or atopic dermatitis (AD) and who were being treated with a biologic agent. Registry data were collected from patients in 21 countries between 2017 and 2022.Patients with type 2 comorbidities treated with anti-IL-5/IL-5 receptor (n = 1257), anti-IgE (n = 421), or anti-IL-4/13 (n = 87) biologic therapies were assessed to determine the association of the type 2 comorbidity on the effectiveness of biologic therapy for the treatment of asthma. Asthma control outcomes (annual asthma exacerbation rate, forced expiratory volume for 1 second % predicted, asthma control based on GINA 2020 criteria, and long-term oral corticosteroid daily use) were assessed before and after biologic therapy.The majority of patients were female (60.6%) and ≥50 years (65.7%). Almost all were never or ex-smokers (97.4%) with asthma onset > 12 years (79.7%) and had an eosinophilic asthma phenotype (95.8%). The majority (83.5%) had more than 1 type 2 comorbidity, with AR being the most common (60.7%). Patients on anti-IL-5/5R therapy generally had more severe asthma and patients on anti-IL-4/13 generally had less severe asthma, although there were fewer subjects treated with anti-IL-4/13 therapy. Overall, all patients had improvement in all the asthma control outcomes on any biologic therapy. However, the subjects with NP versus without NP had greater postbiologic therapy improvement in exacerbation rate, asthma control, and lung function. When adjusted for blood eosinophil count, the difference was still present but not as significant. Patients with CRS with or without NP or patients with NP alone experienced 22% to 23% fewer exacerbations per year and had 56% to 59% higher odds of better postbiologic therapy asthma control compared with subjects without CRS ± NP, or NP alone. AR and AD did not significantly influence biologic agent effectiveness for any outcome assessed.Severe asthma with comorbid CRS ± NP or NP alone may represent a distinct asthma phenotype associated with improved clinical and functional outcomes in response to biologic therapies. Comorbid AR and AD were not associated with improved effectiveness of biologics used to treat severe asthma.Results were limited by clinical data not collected during the coronavirus 2019 pandemic and by variability in the diagnosis and management of type 2 comorbid conditions and in the criteria for initiating biologic therapy between countries. However, this large heterogeneous cohort of asthma patients appears powered to detect possible associations. The overall effectiveness of biologic therapies in treating asthma in patients with type 2 comorbidities is well documented, but there is an emerging conundrum as to which biologic may be the best choice for each patient. These results suggest that asthma patients with certain associated type 2 comorbidities have differing responses to the biologic therapies. Further studies assessing other comorbidities with respect to asthma outcomes while on biologic therapy, as well as direct comparison of the biologic therapies, may help to better personalize the choice of biologic therapy for each patient with severe asthma.