Efficacy and Safety of Biologic Therapies for Uncontrolled Asthma: An Overview of Systematic Reviews.

BACKGROUND

Asthma is a heterogeneous inflammatory disease that can cause substantial morbidity, reduced quality of life, and socioeconomic burden when uncontrolled. Biologic therapies have become central to the management of moderate-to-severe asthma by targeting specific inflammatory pathways.

METHODS

This overview of systematic reviews synthesized evidence on the efficacy and safety of biologic agents for uncontrolled asthma. Searches were conducted in Medline (PubMed), Embase, LILACS, Web of Science, and the Cochrane Library using MeSH and Emtree terms structured according to the PICOT framework. Systematic reviews with meta-analyses or network meta-analyses comparing omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, and tezepelumab were included.

RESULTS

In indirect comparisons, dupilumab and tezepelumab were associated with more favorable outcomes in reducing the annualized exacerbation rate (AER) than benralizumab, mepolizumab, and reslizumab in severe uncontrolled asthma. In eosinophilic asthma, indirect evidence suggested more favorable outcomes with mepolizumab, tezepelumab, and dupilumab across eosinophil-defined subgroups (≥ 400 cells/μL, ≥ 300 cells/μL, ≥ 150 cells/μL, and < 150 cells/μL). In corticosteroid-dependent asthma, benralizumab and dupilumab were associated with more favorable outcomes in selected comparisons. For lung function (FEV1), indirect evidence suggested more favorable outcomes with dupilumab. Regarding asthma control (ACQ), more favorable outcomes were observed with mepolizumab in specific comparisons. Regarding quality of life (AQLQ), more favorable outcomes were observed with omalizumab and tezepelumab in the general and eosinophilic asthma populations, respectively. One indirect comparison suggested lower odds of serious adverse events with mepolizumab.

CONCLUSION

The available evidence suggests that biologic therapies may be effective and generally safe options for uncontrolled asthma, although the methodological quality of most included reviews was critically low. These findings support individualized treatment guided by biomarkers and clinical characteristics and highlight the need for standardized, methodologically rigorous future studies.