Monoclonal Antibodies Targeting IL-5 or IL-5Rα in Eosinophilic Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Abstract

Background: Although the predominant airway inflammation in chronic obstructive pulmonary disease (COPD) is neutrophilic, approximately 20–40% of COPD patients present with eosinophilic airway inflammation. Compared with non-eosinophilic COPD patients, eosinophilic COPD patients are characterized by a greater number of total exacerbations and higher hospitalization rates. Furthermore, anti-interleukin-5 (IL-5) therapy, consisting of monoclonal antibodies (mAbs) targeting IL-5 or IL-5 receptor α (IL-5Rα), has been proven to be effective in severe eosinophilic asthma. This meta-analysis aimed to determine the efficacy and safety of anti-IL-5 therapy in eosinophilic COPD.Methods: We searched the PubMed, Web of Science, Embase, and Cochrane Library databases from inception to August 2020 (updated in June 2021) to identify studies comparing anti-IL-5 therapy (including mepolizumab, benralizumab, and reslizumab) with placebo in eosinophilic COPD patients.Results: Anti-IL-5 therapy was associated with a decrease in acute exacerbation rate (RR 0.89; 95% CI 0.84 to 0.95, I2 = 0%) and the severe adverse events (RR 0.90; 95% CI 0.84 to 0.97, I2 = 0%). However, no significant improvement was observed in pre-bronchodilator forced expiratory volume in 1 s (FEV1) (WMD 0.01; 95% CI −0.01 to 0.03, I2 = 25.9%), SGRQ score (WMD −1.17; 95% CI −2.05 to −0.29, I2 = 0%), and hospital admission rate (RR 0.91; 95% CI 0.78 to 1.07, I2 = 20.8%).Conclusion: Anti-IL-5 therapy significantly reduced the annual acute exacerbation rate and severe adverse events in eosinophilic COPD patients. However, it did not improve lung function, quality of life, and hospitalization rate.

The clinical efficacy of type 2 monoclonal antibodies in eosinophil-associated chronic airway diseases: a meta-analysis

“…The results on FEV1 of asthma and COPD are inconsistent. Even though FEV1 in COPD patients improved, the difference was not statistically significant, which was consistent with previous studies ( 165 – 167 ). Overall, FEV1 considerably improved in asthma patients receiving anti-T2s.…”

Elastin-derived peptides favor type 2 innate lymphoid cells in COPD

“…In COPD, the role of IL-5 and its potential targeting remains a conundrum. Indeed, some studies advocate for the use of anti-IL-5/IL-5R treatment [35][36][37] based on benefits on exacerbations while others call for more research to identify patients that would benefit from IL-5 targeting [38][39][40].…”

A systematic review and integrated analysis of biologics that target Type 2 inflammation to treat COPD with increased peripheral blood eosinophils

“…Zhang, et al. reported an integrated analysis of mepolizumab and benralizumab in eosinophilic COPD, which also double counted placebo in the three-group comparison in the METREO trial for mepolizumab [ 16 ]. Some previous reports considered the study subjects to have eosinophilic COPD [ 8 , 16 ], but this tentative name is confused with COPD with eosinophilic airway inflammation or ACO.…”

“…In phase III clinical trials, these four mAbs reduced moderate-to-severe exacerbations in severe asthma patients with Type 2 airway inflammation [ 2 , 3 , 4 , 5 , 6 ] and are approved to treat severe asthma in Europe, the United States, and Japan. Recently, several biologics were tested in clinical trials for COPD [ 7 , 8 , 9 , 10 , 11 ], and five systematic reviews and meta-analyses evaluated the efficacy of biologics including benralizumab and mepolizumab on COPD patients [ 12 , 13 , 14 , 15 , 16 ]. However, these reports had some statistical problems, and/or compared their efficacy in all COPD patients, as detailed in the discussion section.…”