Background: Several biologic agents have been evaluated in randomised controlled trials (RCTs) and six of them are now approved for patients with severe asthma.

Objective: To assess the efficacy of licensed biologic agents on asthma exacerbations and hospitalisations, lung function (FEV1), symptoms (ACQ), quality of life (AQLQ), oral corticosteroid use and sparing effect, as well as safety in patients with severe asthma.

Methods: We searched MEDLINE, EMBASE and CENTRAL for randomised controlled trials of licensed biologics in severe or uncontrolled asthma (until December 31st, 2022).

Results: We identified 3,666 studies out of which 58 were included in the meta-analysis, with a total of 19,306 patients (10,563 on biologics and 8,743 controls). 5,983 patients received omalizumab (anti-IgE), 697 mepolizumab (anti-IL5), 393 reslizumab (anti-IL5), 1,798 benralizumab (anti-IL5R?), 945 dupilumab (anti-IL4R?), and 747 tezepelumab (anti-TSLP). Biologic agents were associated with a 45% reduction in the annualized rate of asthma exacerbations (risk ratio, RR, 0.55, 95% CI 0.51 to 0.61), a mean increase in the FEV1 by 0.110 litres (95% CI 0.80 to 0.130), a reduction in ACQ by 0.34 points (95% CI -0.43 to -0.25), and an increase in AQLQ by 0.36 points (95% CI 0.23 to 0.48). We also assessed safety and performed analyses by agent and markers of T2 high inflammation.

Conclusions: Biologic agents reduced exacerbations and symptoms, increased lung function, and improved quality of life in severe asthma, with acceptable safety profile.