Anti-IL5 treatments in severe asthma by blood eosinophil thresholds: indirect treatment comparison

Publication date: Available online 8 September 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): William Busse, Geoffrey Chupp, Hiroyuki Nagase, Frank C. Albers, Scott Doyle, Qin Shen, Daniel J. Bratton, Necdet B. Gunsoy

Abstract

Background

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

Objective

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

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 with SEA. Endpoints included annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ) score and forced expiratory volume in 1 second. An ITC was performed in patients with ACQ ≥1.5 and stratified by baseline blood eosinophil counts.

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 subgroups. Mepolizumab reduced clinically significant exacerbations by 34%–45% versus benralizumab across subgroups (rate ratio[RR] [95%CI]: ≥400 cells/μL: 0.55[0.35,0.87]; ≥300 cells/μL: 0.61[0.37,0.99]; ≥150 cells/μL: 0.66[0.49,0.89]; all p<0.05) and by 45% versus reslizumab in the ≥400 cells/μL subgroup (RR[95%CI]: 0.55[0.36,0.85], p=0.007). Asthma control was significantly improved with mepolizumab versus benralizumab (all subgroups: p<0.05), and versus reslizumab in the ≥400 cells/μL subgroup (p=0.004). Benralizumab significantly improved lung function versus reslizumab in the ≥400 cells/μL subgroup (p=0.025).

Conclusions

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

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