Effect of Anti-IL5, Anti-IL5R, Anti-IL13 Therapy on Asthma Exacerbations: A Network Meta-analysis

Abstract

Background: Several new treatments for severe asthma have become available in the last decade; yet, little data exist to guide their use in specific patient populations.

Objective: A network meta-analysis was conducted comparing the efficacy of FDA-approved monoclonal antibody therapies in preventing exacerbations in patients with severe eosinophilic asthma.

Methods: PubMed and Ovid were searched from inception until July 2019 for randomized controlled trials that studied the efficacy of benralizumab, dupilumab, mepolizumab, and reslizumab, in preventing acute exacerbations of asthma. Studies were included if they reported data for patients with severe eosinophilic asthma (defined in this meta-analysis as absolute eosinophil count ≥ 250 cells/μL). Annualized rate ratios for asthma exacerbations (during treatment) were calculated and converted to log rate ratios. Direct and indirect treatment estimates (for inter-drug differences) were analyzed using frequentist network meta-analysis methodology in R and treatments were ranked based on P-scores.

Results: In total, nine studies were included in the final analysis. Network meta-analysis revealed that all drugs were superior to placebo in preventing rates of asthma exacerbation in the study population and no inter-drug differences existed. Dupilumab was found to have the greatest magnitudes of effect on decreasing log rate ratio of asthma exacerbation based on P-score (0.83).

Conclusion: Benralizumab, dupilumab, mepolizumab, and reslizumab are all associated with decreased asthma exacerbations in patients with eosinophilic asthma, with no significant inter-drug differences.

Keywords: Benralizumab; Dupilumab; Eosinophilic asthma; Mepolizumab; Reslizumab.

Fig. 1

Selection of studies. Details on studies excluded as shown in figure are provided in Appendix/Data Supplement

Fig. 2

Meta-analysis of pooled log rate ratios for asthma exacerbations. The size of the square indicates the weight of the effect size as determined by the number of studies and participants. CI confidence interval

Fig. 3

Network evidence graph. Graph plotted on a two-dimensional plane, in which the connecting lines between treatment names display the treatment comparisons (thickness of lines indicating number of studies in each comparison)

Fig. 4

Comparison-adjusted funnel plot. Comparison-adjusted funnel plot for publication bias assessment with statistical tests for plot asymmetry reported in top left corner