Impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in patients with severe asthma

Background There is little agreement on clinically useful criteria for identifying real-world responders to biologic treatments for asthma. Objective To investigate the impact of pre-biologic impairment on meeting domain-specific biologic responder definitions in adults with severe asthma. Methods This was a longitudinal, cohort study across 22 countries participating in the International Severe Asthma Registry (https://isaregistries.org/) from May 2017 to January 2023. Change in four asthma domains (exacerbation rate, asthma control, long-term oral corticosteroid [LTOCS] dose, and lung function) was assessed from biologic initiation to one year post-treatment (minimum 24 weeks). Pre- to post-biologic changes for responders and non-responders were described along a categorical gradient for each domain derived from pre-biologic distributions (exacerbation rate: 0 to 6+/year; asthma control: well-controlled to uncontrolled; LTOCS: 0 to >30 mg/day; ppFEV1: <50 to ≥80%). Results Percentage of biologic responders (i.e., those with a category improvement pre- to post-biologic) varied by domain and increased with greater pre-biologic impairment, increasing from 70.2 to 90.0% for exacerbation rate, 46.3 to 52.3% for asthma control, 31.1 to 58.5% for LTOCS daily dose, and 35.8 to 50.6% for ppFEV1. The proportion of patients showing improvement post-biologic tended to be greater for anti–IL-5/5R compared to anti-IgE for exacerbation, asthma control, and ppFEV1 domains, irrespective of pre-biologic impairment. Conclusion Our results provide realistic outcome-specific post-biologic expectations for both physicians and patients, will be foundational to inform future work on a multi-dimensional approach to define and assess biologic responders and response, and may enhance appropriate patient selection for biologic therapies.