The Clinical Efficacy of Type 2 Inflammation-Specific Agents Targeting Interleukins in Reducing Exacerbations in Severe Asthma: A Meta-Analysis

Purpose: Monoclonal antibodies against type 2 inflammatory pathways are currently promising therapeutics for severe asthma. The aim of this study was to determine how well type 2 (T2) inflammation-specific agents targeting interleukins reduce the rate of asthma exacerbations (AE) in patients with severe asthma. Materials and Methods: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register. The primary outcome was the reduction rate of annualized AEs. Results: We analyzed 17 studies comprising 11800 subjects. A total of 6197 patients received T2-specific agents (benralizumab, dupilumab, lebrikizumab, mepolizumab, reslizumab, and tralokinumab). Overall, T2-specific agents were significantly associated with a lower risk of AE, compared with placebo [rate ratio (RR) 0.58, 95% confidence interval (CI) 0.51 to 0.66]. Among all studied agents, only tralokinumab did not demonstrate a reduction in AE. The efficacy of T2-specific agents in reducing AE was maintained regardless of the pathway used. A subgroup analysis indicated that T2-specific agents further reduced the risk of AE in patients with eosinophil counts of ≥300 cells/μL (RR 0.41, 95% CI 0.32 to 0.53). Conclusion: Our findings suggest that T2-specific agents are significantly associated with a reduced rate of AE, compared with placebo. Their efficacy appears to be enhanced in patients with eosinophil counts of ≥300 cells/μL.