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Differences between biologics for eosinophilic asthma do not meet clinically important thresholds

Published: June 27, 2022

Evidence on the comparative efficacy and safety of the monoclonal antibodies currently approved for the treatment of asthma is sparse. Additional evidence is however needed to optimize the value of these therapies.

In this edition of The Journal of Allergy and Clinical Immunology (JACI), Akenroye et al. report the results of a systematic review and indirect treatment comparison of the efficacy and safety of mepolizumab, benralizumab, and dupilumab in individuals with eosinophilic asthma. Outcomes of interest included the exacerbation rate ratio, mean difference in prebronchodilator forced expiratory volume in one second (FEV1) and asthma control questionnaire (ACQ), and odds of serious adverse events. The biologics were ranked based on the size and precision of the effect estimate. In addition, they evaluated if the differences between these biologics met minimal clinically important differences.

Eight studies of about 6,500 individuals were included. In individuals with eosinophil counts of =300 cells per microliter, dupilumab and mepolizumab were associated with significantly fewer exacerbations compared to benralizumab. Dupilumab ranked highest in improving FEV1, but this was not significantly different from mepolizumab and benralizumab. Mepolizumab was significantly better than benralizumab in improving the ACQ. Although dupilumab ranked highest in improving exacerbations and lung function, the probability of dupilumab leading to halving of the exacerbation rate in the mepolizumab or benralizumab group was <5% and probability of improving FEV1 by =100 milliliters compared to mepolizumab or benralizumab was <1%. In individuals with eosinophil count of 150 to 299 cells per microliter, the biologics were not significantly different in their effects on exacerbations and FEV1. However, there was limited power to detect differences in this subgroup due to fewer number of studies. Dupilumab had the highest odds of serious adverse events. This was however not different from the odds of serious adverse events in the placebo arm.

There are minimal differences in the comparative efficacy of dupilumab and mepolizumab, and benralizumab in the treatment of eosinophilic asthma. However, in individuals with eosinophil counts =300 cells per microliter, dupilumab and mepolizumab ranked highest in improving exacerbation rates and asthma control questionnaire, while dupilumab and benralizumab ranked highest in improving exacerbation rates and lung function in individuals with eosinophil count of =150 cells per microliter. Additional work is needed to evaluate the comparative effectiveness of biologics in the treatment of asthma particularly in real-world populations which may differ from trial populations.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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