Abstract Rationale Chronic obstructive pulmonary disease (COPD) is a common lung condition that often contributes to repeated hospitalizations and significant mortality. Roflumilast is an oral phosphodiesterase-4 inhibitor that is used to reduce exacerbations in patients with severe COPD and chronic bronchitis. However, newer medications such as ensifentrine, a dual PDE3/4 inhibitor with both bronchodilatory and anti-inflammatory properties, may offer therapeutic advantages. To our knowledge, this is the first retrospective cohort study using a large, multicenter database directly comparing outcomes in patients with COPD treated with ensifentrine versus roflumilast. Methods Using the TriNetX platform screening across 65 U.S. healthcare organizations, patients with at least 2 COPD exacerbations within the last 3 years (2022-2025) were identified and stratified by new ensifentrine or roflumilast prescriptions. Patients in the ensifentrine cohort were excluded if they had ever received roflumilast, and vice versa. Propensity-score matching (PSM) was used to balance age, sex, ethnicity, nicotine dependence, oxygen dependence, prednisone use, hospital utilization, and other comorbidities. The primary outcome was the incidence of acute COPD exacerbation within 3 and 6 months following medication initiation. Secondary outcomes included mechanical ventilation, all-cause mortality, acute respiratory failure, emergency room visits, hospital admission, pneumonia, major cardiovascular events, diarrhea, and depression/anxiety. Results A total of 13,516 patients were identified in the roflumilast group and 697 patients in the ensifentrine group. After matching, 697 patients in each cohort were evaluated for outcomes. There was no significant difference in acute COPD exacerbations at 3 months, while at 6 months patients receiving ensifentrine had a significantly lower risk of exacerbation (RR: 0.78, 95% CI 0.68-0.90). Also at 3 months, patients prescribed ensifentrine had a lower rate of hospitalization (RR: 0.76, 95% CI 0.62-0.94). At 6 months, the patients prescribed ensifentrine demonstrated lower risk of emergency department visits (RR: 0.76, 95% CI 0.64-0.92), hospital admissions (RR: 0.73, 95% CI 0.61-0.87), pneumonia (RR: 0.65, 95% CI 0.51-0.84), diarrhea (RR: 0.42, 95% CI 0.25-0.71), and depression/anxiety (RR: 0.81, 95% CI 0.67-0.98). No significant differences were observed in acute respiratory failure, mechanical ventilation, mortality, or cardiovascular events. Conclusion Ensifentrine demonstrated lower rates of COPD exacerbations, hospitalization, pneumonia, and other secondary outcomes compared to roflumilast. This is the first study directly evaluating outcomes between ensifentrine and roflumilast, supporting the need for future prospective studies to help guide clinicians on decision making around the numerous COPD adjunctive treatment options. This abstract is funded by: None
Shaik et al. (Fri,) studied this question.
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