Clinical Effectiveness of Roflumilast in Patients With Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis.

Chronic obstructive pulmonary disease (COPD) is a major contributor to global morbidity and mortality, with acute exacerbations accelerating disease progression and substantially increasing healthcare utilization and costs. To evaluate the available evidence on roflumilast, an oral phosphodiesterase-4 inhibitor, we performed a systematic review and meta-analysis. We searched PubMed/MEDLINE, Embase, CENTRAL, Web of Science, Scopus, and ClinicalTrials.gov from 1 January 2011 to 15 July 2026 for studies evaluating roflumilast in adults with COPD. Ten studies met the inclusion criteria, comprising randomized controlled trials, a quasi-experimental trial, and an observational cohort study. Roflumilast was associated with statistically significant improvements in forced expiratory volume in one second (FEV1) compared with control (pooled mean difference: 0.06 L, 95% CI: 0.04-0.08; I² = 72%) and forced vital capacity (FVC) (mean difference: 0.07 L, 95% CI: 0.02-0.12; I² = 78%), although these improvements approximate or fall below the established minimal clinically important difference for FEV1 (100 mL), suggesting modest clinical benefit at the population level. No statistically significant reduction in exacerbation risk was observed (risk ratio: 1.31, 95% CI: 0.73-2.36; I² = 76%); however, given the substantial heterogeneity and wide confidence interval, this finding should not be interpreted as evidence of no effect, particularly as individual trial data suggest exacerbation benefit may be concentrated in patients with more severe disease or frequent prior exacerbations. No significant differences were found for quality of life as measured by the St. George's Respiratory Questionnaire (mean difference: -6.26, 95% CI: -21.70 to 9.18; I² = 78%) or all-cause mortality (risk ratio: 1.02, 95% CI: 0.54-1.91; I² = 0%). Roflumilast produces statistically significant but modest improvements in lung function in patients with COPD; its effects on exacerbations, quality of life, and mortality remain uncertain, given substantial heterogeneity across studies. These findings support current guideline recommendations restricting roflumilast use to specific patient phenotypes, and further large-scale trials in more homogeneous populations are warranted to clarify its role in COPD management.