Clinical outcomes and remission trajectories in obese and non-obese patients with severe asthma treated with biologics: a retrospective longitudinal cohort study from the Severe Asthma Network Italy (SANI) registry

Background: Obesity is common in severe asthma and associated with poorer control, reduced lung function, and comorbidities. Registry data suggest that obesity may lessen biologic effectiveness, but findings are inconsistent. We assessed the impact of obesity on long-term outcomes. Methods: We retrospectively analysed 2098 adults with severe asthma enrolled in the Italian Severe Asthma Network registry between 2017 and 2024. Patients were classified as biologic-naïve, initiating treatment during observation, or on-treatment at registry entry. Obesity was defined as body mass index (BMI) ≥30 kg/m2. Outcomes included exacerbations, Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ), Forced Expiratory Volume in 1 second (FEV1), and remission, defined as ≥12 consecutive months meeting prespecified criteria (no exacerbations or oral corticosteroids, ACT ≥ 20, FEV1 ≥ 80% predicted). Longitudinal changes were assessed using zero-inflated negative binomial and linear mixed-effects models; remission by Kaplan–Meier and Cox models. Findings: Of 2098 patients (1118 biologic-naïve; 980 on biologics at inclusion), 405 (19.3%) were obese. At baseline, obese patients showed poorer control, lower AQLQ, more comorbidities, but fewer nasal polyps and lower type-2 inflammation. During follow-up, exacerbations, ACT, AQLQ, and FEV1 improved similarly in obese and non-obese, without significant differences across naïve or on-treatment cohorts. At 24 months, cumulative remission probability was 22–25%. Obesity did not influence remission likelihood (HR for BMI ≥ 30: 0.88 [95% CI 0.57–1.37] in naïve; 0.91 [0.44–1.89] in on-treatment). Interpretation: Biologics remain efficacious in obese patients with severe asthma. Treatment achieved comparable improvement trajectories across all outcomes regardless of BMI, highlighting the importance of long-term follow-up. Funding: CN00000041_CN3_Spoke_#4_PNRR.