Biologic agents licensed for severe asthma: a systematic review and meta-analysis of randomised controlled trials

Abstract

Background: Six biologic agents are now approved for patients with severe asthma. This meta-analysis aimed to assess the efficacy and safety of licensed biologic agents in patients with severe asthma, including the recently approved tezepelumab. Methods: We searched MEDLINE, Embase and CENTRAL to identify randomised controlled trials involving licensed biologics until 31 January 2023. We used random-effects meta-analysis models for efficacy, including subgroup analyses by individual agents and markers of T2-high inflammation (blood eosinophils and fractional exhaled nitric oxide), and assessed safety. Results: 48 studies with 16 350 patients were included in the meta-analysis. Biologics were associated with a 44% reduction in the annualised rate of asthma exacerbations (rate ratio 0.56, 95% CI 0.51–0.62) and 60% reduction of hospitalisations (rate ratio 0.40, 95% CI 0.27–0.60), a mean increase in the forced expiratory volume in 1 s of 0.11 L (95% CI 0.09–0.14), a reduction in asthma control questionnaire by 0.34 points (95% CI −0.46–−0.23) and an increase in asthma quality of life questionnaire by 0.38 points (95% CI 0.26–0.49). There was heterogeneity between different classes of biologics in certain outcomes, with overall greater efficacy in patients with T2 inflammation. Overall, biologics exhibited a favourable safety profile. Conclusions: This comprehensive meta-analysis demonstrated that licensed asthma biologics reduce exacerbations and hospitalisations, improve lung function, asthma control and quality of life, and limit the use of systemic corticosteroids, with a favourable safety profile. These effects are more prominent in patients with evidence of T2 inflammation.