Hammadeh Bara M, Younis Osama M, Alsufi Muaath I, Idrees Muhammad, Hussein Ayham Mohammad, Aldalati Abdullah Yousef, Qtaishat Fares A, Qatawneh Banan, Bugazia Al, Hamed Raed A
Faculty of Medicine, Al-Balqa' Applied University, Salt 11185, Jordan.
Faculty of Medicine, University of Jordan, Amman, Jordan.
Ther Adv Respir Dis. 2025 Jan-Dec;19:17534666251347775. doi: 10.1177/17534666251347775. Epub 2025 Jun 20.
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease marked by airway inflammation and obstruction. Ensifentrine is a novel inhaled PDE3 and PDE4 inhibitor with both bronchodilator and anti-inflammatory effects.
Comprehensively review the available evidence on ensifentrine and its potential role in COPD management.
Systematic review and meta-analysis with trial sequential analysis of randomized clinical trials.
We systematically searched PubMed, Scopus, ScienceDirect, Cochrane Library, and Medline for clinical trials published between 2018 and August 2024 that evaluated the safety and efficacy of ensifentrine in patients with COPD. We assessed study quality using the RoB 2 tool and conducted the meta-analysis with the "meta" package in R (version 4.3.2), using the mean difference with a 95% confidence interval to evaluate changes in outcomes.
Five studies met the predefined inclusion criteria with 2519 participants. At week 12, the pooled analysis indicated that forced expiratory volume in 1 s (FEV) and trough FEV were significantly increased in the ensifentrine group (mean difference (MD): 91.32; 95% CI: 69.63 to 113.01) and (MD: 40.90; 95% CI: 19.65 to 62.15), respectively. At week 24, the pooled analysis indicated that the evaluating respiratory symptoms total score was significantly decreased in the ensifentrine group (MD: -0.81; 95% CI: -1.36 to -0.27), transition dyspnea index score was significantly increased in the ensifentrine group (MD: 0.96; 95% CI: 0.62 to 1.29), no significant difference was observed in rescue medication use (MD: -0.30; 95% CI: -0.60 to 0.00), and no significant difference was observed in St. George's Respiratory Questionnaire total score (MD: -1.46; 95% CI: -3.22 to 0.30). Based on subgroup analysis, higher doses were associated with more favorable results.
In conclusion, owing to its dual effects, ensifentrine has a significant impact on improving pulmonary function and quality of life with minimal side effects. Promising results are expected if implied by synergizing with other drugs, however, more studies are needed to study the long-term effect on disease progression.
The study protocol was published via PROSPERO: International Prospective Register of Systematic Reviews (#CRD42024570799).
慢性阻塞性肺疾病（COPD）是一种以气道炎症和阻塞为特征的进行性肺部疾病。恩昔芬净是一种新型吸入性磷酸二酯酶3（PDE3）和磷酸二酯酶4（PDE4）抑制剂，具有支气管扩张和抗炎作用。
全面综述关于恩昔芬净及其在COPD管理中潜在作用的现有证据。
对随机临床试验进行系统评价和荟萃分析，并进行试验序贯分析。
我们系统检索了PubMed、Scopus、ScienceDirect、Cochrane图书馆和Medline，以查找2018年至2024年8月期间发表的评估恩昔芬净在COPD患者中安全性和有效性的临床试验。我们使用RoB 2工具评估研究质量，并使用R（版本4.3.2）中的“meta”包进行荟萃分析，使用平均差值和95%置信区间来评估结局的变化。
五项研究符合预定义的纳入标准，共有2519名参与者。在第12周，汇总分析表明，恩昔芬净组的1秒用力呼气量（FEV₁）和谷值FEV₁显著增加（平均差值（MD）：91.32；95%置信区间：69.63至113.01）和（MD：40.90；95%置信区间：19.65至62.15）。在第24周，汇总分析表明，恩昔芬净组的评估呼吸症状总分显著降低（MD：-0.81；95%置信区间：-1.36至-0.27），过渡性呼吸困难指数评分显著增加（MD：0.96；95%置信区间：0.62至1.29），在使用急救药物方面未观察到显著差异（MD：-0.30；95%置信区间：-0.60至0.00），在圣乔治呼吸问卷总分方面也未观察到显著差异（MD：-1.46；95%置信区间：-3.22至0.30）。基于亚组分析，较高剂量与更有利的结果相关。
总之，由于其双重作用，恩昔芬净对改善肺功能和生活质量具有显著影响，且副作用最小。如果与其他药物协同使用，有望取得更好的效果，然而，需要更多研究来探讨其对疾病进展的长期影响。
该研究方案已通过PROSPERO：国际系统评价前瞻性注册库（#CRD42024570799）发表。
