TSLP and IL4/13 blockade led to greater improvements in eosinophilic asthma
Published: December 16, 2022
Multiple biologics are currently approved by the U.S. Food and Drug Administration for the treatment of eosinophilic asthma. With many patients being eligible for two or more of these therapies, and randomized trials showing all these therapies as effective, there is wide interest in potential differences in the efficacy of these biologics, and if any of these differences meet minimal clinically important thresholds.
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Nopsopon et al evaluated the comparative efficacy of tezepelumab to dupilumab, mepolizumab, and benralizumab in improving asthma exacerbation rates, prebronchodilator forced expiratory volume in one second (FEV1), and the asthma control questionnaire (ACQ) in patients with asthma and eosinophils ≥300 cells per microliter. They identified relevant randomized controlled trials through a systematic review and conducted a network meta-analysis to indirectly compare the four biologics. Furthermore, the authors explored the probabilities that any identified differences between a pair of therapies would meet prespecified minimal clinically important thresholds.
Ten clinical trials with a study population of 9,201 patients were included. Compared to mepolizumab and benralizumab, tezepelumab and dupilumab were associated with greater reductions in the exacerbation rates and in lung function improvement. Compared to the biologic with the lowest effect for each outcome, tezepelumab and dupilumab were associated with a 75% and 62% probability of reducing the exacerbation rate of benralizumab by 30% respectively but had a probability of less than 50% in halving benralizumab’s exacerbation rate; dupilumab was associated with over 90% probability of improving FEV1 by 50 mL or more compared to mepolizumab while tezepelumab had a 65% probability of improving FEV1 by 30 mL or more compared to mepolizumab. The probability of improving FEV1 by ≥100 mL over mepolizumab’s effect was 0 for all comparators. Although mepolizumab ranked the highest in improving ACQ, it had about a 50% probability of improving ACQ by 0.5 compared to benralizumab.
The authors concluded that while the magnitude of differences between biologics generally did not reach clinically important thresholds, there is evidence that tezepelumab and dupilumab yielded greater improvements in exacerbation rate reductions and lung function improvement compared to benralizumab and mepolizumab. However, more information from real-world settings is needed for higher certainty and generalizability of the results.
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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