Biologics and immunotherapy
Anti–IL-5 treatments in patients with severe asthma by blood eosinophil thresholds: Indirect treatment comparison

https://doi.org/10.1016/j.jaci.2018.08.031Get rights and content
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Background

Three anti–IL-5 pathway–directed therapies are approved for use in patients with severe eosinophilic asthma (SEA); however, no head-to-head comparison data are available.

Objective

We sought to compare the efficacy of licensed doses of mepolizumab, benralizumab, and reslizumab in patients with SEA, according to baseline blood eosinophil counts.

Methods

This indirect treatment comparison (ITC) used data from a Cochrane review and independent searches. Eligible studies were randomized controlled trials in patients aged 12 years or greater with SEA. End points included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire score and FEV1. An ITC was performed in patients with Asthma Control Questionnaire scores of 1.5 or greater and stratified by baseline blood eosinophil count.

Results

Eleven studies were included. All treatments significantly reduced the rate of clinically significant exacerbations and improved asthma control versus placebo in all blood eosinophil count subgroups. Mepolizumab reduced clinically significant exacerbations by 34% to 45% versus benralizumab across subgroups (rate ratio ≥400 cells/μL: 0.55 [95% CI, 0.35-0.87]; ≥300 cells/μL: 0.61 [95% CI, 0.37-0.99]; and ≥150 cells/μL: 0.66 [95% CI, 0.49-0.89]; all P < .05) and by 45% versus reslizumab in the 400 cells/μL or greater subgroup (rate ratio, 0.55 [95% CI, 0.36-0.85]; P = .007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: P < .05) and versus reslizumab in the 400 cells/μL or greater subgroup (P = .004). Benralizumab significantly improved lung function versus reslizumab in the 400 cells/μL or greater subgroup (P = .025).

Conclusions

This ITC of the licensed doses suggests that mepolizumab was associated with significantly greater improvements in clinically significant exacerbations and asthma control compared with reslizumab or benralizumab in patients with similar blood eosinophil counts.

Key words

Benralizumab
indirect treatment comparison
mepolizumab
network meta-analysis
reslizumab
severe eosinophilic asthma

Abbreviations used

ACQ
Asthma Control Questionnaire
ED
Emergency department
GINA
Global Initiative for Asthma
ITC
Indirect treatment comparison
ITT
Intent-to-treat
OCS
Oral corticosteroid
Q4W
Every 4 weeks
Q8W
Every 8 weeks
RR
Rate ratio
SAE
Serious adverse event
SEA
Severe eosinophilic asthma

Cited by (0)

This indirect treatment comparison was funded by GlaxoSmithKline (GSK ID no. 209020/HO-18-19164). GlaxoSmithKline had a role in the design of the analysis, data collection, data analysis, and data interpretation. The funder did not place any restrictions on access to the data or statements made in the manuscript. The decision to submit for publication was that of the authors alone.

Disclosure of potential conflict of interest: W. Busse reports personal fees from Novartis, AstraZeneca, GlaxoSmithKline, Genentech, Regeneron, Sanofi, Boston Scientific, and ICON Clinical Research; royalties from Elsevier; and grants from the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) and the NIH/National Heart, Lung, and Blood Institute (NHLBI). G. Chupp has acted as a consultant, for AstraZeneca, Genentech, Boehringer Ingelheim, and Teva; attended a speakers' bureau with AstraZeneca, Genentech, and Circassia; and received research grants from AstraZeneca and institutional grants from AstraZeneca, Genentech, Boehringer Ingelheim, and GlaxoSmithKline. H. Nagase has attended advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis and received speaker's fees from AstraZeneca, Boehringer Ingelheim, Kyorin Pharmaceutical, and Novartis. F. C. Albers, S. Doyle, Q. Shen, D. J. Bratton, and N. B. Gunsoy are employees of and hold stocks/shares in GlaxoSmithKline.