Efficacy and safety of ensifentrine, a novel phosphodiesterase 3 and 4 inhibitor, in chronic obstructive pulmonary disease: A systematic review and meta-analysis

Respir Investig. 2025 Jan;63(1):146-155. doi: 10.1016/j.resinv.2024.12.012. Epub 2024 Dec 18.

Abstract

Background: We evaluated the efficacy and safety of Ensifentrine in COPD via a systematic review and meta-analysis of randomized controlled trials (RCTs).

Methods: We performed a detailed literature search on Medline (via PubMed), Scopus, Google Scholar, and Cochrane on the basis of pre-specified eligibility criteria. We used Review Manager to calculate pooled mean differences (MD) and 95% Confidence Interval (CI) using a random effects model. The Cochrane's Risk of Bias 2 (RoB-2) tool was used to assess the risk of bias in the included RCTs.

Results: A total of 4 studies, consisting of 2020 patients, were included in the meta-analysis. The mean age ranged from 62.5 years to 65.5 years in the included studies. All the included studies were at low risk of bias. Ensifentrine 3 mg dose significantly improved the mean peak Forced Expiratory Volume-1 (FEV-1), morning trough FEV-1, TDI score, ERS score, and SGRQ-C score as compared to the placebo, yielding a pooled MD of 149.76 (95% CI, 127.9 to 171.6), 43.93 (95% CI, 23.82 to 64.05), 0.92 (95% CI, 0.64 to 1.21, -1.20 (95% CI, -1.99 to -0.40), and -1.92 (95% CI, -3.24 to -0.59), respectively.

Conclusion: Ensifentrine is associated with improvements in outcomes related to COPD symptoms such as peak FEV-1, morning trough FEV-1 and TDI in the patients suffering from this chronic disease. It is also associated with improved quality of life as seen by E-RS score and SGRQ-C score.

Keywords: COPD; Dual PDE3 and PDE4 inhibitors; Ensifentrine; Meta analysis; Phosphodiesterase inhibitors.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Aged
  • Forced Expiratory Volume
  • Humans
  • Isoquinolines / administration & dosage
  • Isoquinolines / adverse effects
  • Isoquinolines / therapeutic use
  • Middle Aged
  • Phosphodiesterase 3 Inhibitors / administration & dosage
  • Phosphodiesterase 3 Inhibitors / adverse effects
  • Phosphodiesterase 3 Inhibitors / therapeutic use
  • Phosphodiesterase 4 Inhibitors / administration & dosage
  • Phosphodiesterase 4 Inhibitors / adverse effects
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pyrimidinones
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • ensifentrine
  • Phosphodiesterase 3 Inhibitors
  • Phosphodiesterase 4 Inhibitors
  • Isoquinolines
  • Pyrimidinones