Introduction: The latest evidence revealed that dupilumab, an interleukin-4 (IL-4) and interleukin-13 (IL-13) blocker, significantly reduces the exacerbation risk in patients with chronic obstructive pulmonary disease (COPD). The efficacy of dupilumab compared with conventional inhaled drugs remains incompletely determined. This study aimed to investigate the comparative efficacy of dupilumab and conventional inhaled drugs in patients with stable COPD.

Material and methods: This study retrieved randomised clinical trials (RCTs) with follow-up ≥ 48 weeks on long-acting β-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), inhaled corticosteroids (ICSs), and dupilumab in the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases. The information on eligible studies was extracted after the screening. The comparative efficacy of 4 drugs and their combinations in acute exacerbation and mortality was assessed using Bayesian network meta-analysis models.

Results: This network meta-analysis identified 69 eligible RCTs on 7 classes of drug therapies after stepwise screening and included 125,331 COPD patients. Compared with placebo, the 7 drug interventions significantly reduced the risk of acute exacerbation, and the reduction degree increased with the incremental use of drug classes. ICS/LABA/LAMA/dupilumab was the most effective in decreasing exacerbation risk (OR = 0.561 [95% CI: 0.387-0.810]), followed by ICS/LABA/LAMA (OR = 0.717 [95% CI: 0.626-0.817]). The 7 drug therapies were not significantly associated with a lower risk of death compared to placebo. Nevertheless, ICS/LABA/LAMA/dupilumab is the most likely to be effective in decreasing mortality.

Conclusions: The incremental use of combinations of conventional and novel drugs contributed to the long-term benefits in acute exacerbation but not death in COPD. The optimal drug combination in terms of acute COPD exacerbation was ICS/LABA/LAMA/dupilumab.

Keywords: chronic obstructive pulmonary disease; drug therapy; exacerbation; mortality; network meta-analysis.

Copyright: © 2024 Termedia & Banach.

简介： 最新的证据表明，dupilumab（一种IL-4和IL-13阻断剂）显著降低了慢性阻塞性肺疾病（COPD）患者的急性加重风险。与传统吸入药物相比，dupilumab的疗效仍不完全确定。本研究旨在调查dupilumab与传统吸入药物在稳定期COPD患者中的比较疗效。

材料和方法： 本研究从PubMed、EMBASE和Cochrane中心对照试验注册数据库中检索了关于长效β受体激动剂（LABA）、长效毒蕈碱受体拮抗剂（LAMA）和吸入性皮质类固醇（ICS），以及dupilumab的随访期≥48周的随机临床试验。筛选后提取符合条件的研究信息，利用贝叶斯网络荟萃分析模型评估了4种药物及其组合在急性加重和死亡方面的比较疗效。

结果： 本次网络荟萃分析通过逐步筛选确定了7类药物治疗的69项符合标准的随机临床试验，涉及125,331名COPD患者。与安慰剂相比，7种药物干预显著降低了急性加重的风险，并且随着使用的药物类别增加而降低风险的程度也增加。ICS/LABA/LAMA/dupilumab在减少急性加重风险方面最有效（OR = 0.561 [95% CI: 0.387-0.810]），其次是ICS/LABA/LAMA (OR = 0.717 [95% CI: 0.626-0.817])。这7种药物疗法与降低死亡风险之间没有显著关联，然而，使用ICS/LABA/LAMA/dupilumab最有可能有效减少死亡。

结论： 传统和新型药物组合的逐步增加对COPD患者的急性加重长期获益有贡献，但不包括降低死亡风险。在急性COPD加重方面最优的药物组合是ICS/LABA/LAMA/dupilumab。

关键词： 慢性阻塞性肺疾病；药物治疗；急性加重；死亡率；网络荟萃分析。