Biologics in severe asthma: from precision phenotyping to clinical remission

To critically appraise the current landscape of biologic therapies for severe asthma, synthesizing evidence on biomarker-driven strategies, and evaluating the evolving therapeutic goal of clinical remission.

A systematic search of PubMed, Embase, and Cochrane Library databases was conducted for relevant literature published up to December 2025. We included pivotal randomized controlled trials, real-world evidence studies, systematic reviews, and meta-analyses focusing on approved biologics (omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) and emerging agents for severe asthma.

Biologic therapies have consistently demonstrated significant efficacy in reducing exacerbation rates (reductions ranging from 26% to 56% vs. placebo in pivotal trials) and oral corticosteroid dependence, while improving lung function and quality of life. Biomarkers such as blood eosinophils, fractional exhaled nitric oxide (FeNO), and serum IgE are crucial for guiding treatment selection. A substantial proportion of patients (ranging from 32% to 50% in observational studies) can achieve clinical remission, a composite endpoint including symptom freedom, no exacerbations, and OCS independence. Tezepelumab has shown efficacy in a broader population, including patients with lower T2 inflammation.

The management of severe asthma has shifted to a precision medicine paradigm based on molecular phenotyping. Biologics have made clinical remission an attainable goal for many patients. Future research must focus on therapies for non-type 2 asthma, refining dynamic biomarkers, and establishing long-term disease-modifying effects.