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Comparison of anti‐interleukin‐5 therapies in patients with severe asthma: global and indirect meta‐analyses of randomized placebo‐controlled trials
Author(s) -
Cabon Y.,
Molinari N.,
Marin G.,
Vachier I.,
Gamez A. S.,
Chanez P.,
Bourdin A.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12853
Subject(s) - medicine , placebo , adverse effect , exacerbation , mepolizumab , benralizumab , subgroup analysis , asthma , randomized controlled trial , meta analysis , gastroenterology , eosinophil , pathology , alternative medicine
Summary Inconsistent results have been reported regarding IL ‐5 blockade treatment in asthma. There were no direct between‐treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCT s with anti‐ IL 5 treatments for patients with asthma over the 1990‐September 2015 period. RCT s were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV 1 changes, ACQ ‐5 improvement, adverse events and serious adverse events. A global meta‐analysis was first conducted followed by an indirect comparison of each IL ‐5‐targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta‐analysis. IL ‐5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29–50] ( P < 0.01, I 2 = 0.61). ACQ ‐5 was significantly improved vs. placebo but below the recognized MCID level (−0.31 [−0.41, −0.21], P < 0.01, I 2 = 0.11). FEV 1 changes from baseline were improved vs. placebo by 0.09 L [0.05–0.12] ( P < 0.01, I 2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm 3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL ‐5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.