Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Background: Roflumilast, a phosphodiesterase 4 inhibitor, has been shown to improve lung function and reduce exacerbation rates, but is associated with adverse events (AEs). The purpose of this study was to systematically review the clinical effectiveness and safety of roflumilast.

Methods: A systematic search was made of MEDLINE, Cochrane trials database, DARE and CINAHL. Randomized, controlled trials of more than 12 weeks' duration comparing roflumilast with placebo were reviewed. Studies were pooled to yield relative risk (RR), incident rate difference or weighted mean differences with 95% confidence intervals (CIs).

Results: Eight trials (8698 patients) met the inclusion criteria. Roflumilast significantly reduced moderate to severe exacerbations (RR 0.85; 95% CI 0.80-0.91) compared with placebo, but not severe exacerbations (RR 0.83; 95% CI 0.68-1.01) or mortality (RR 0.90; 95% CI 0.63-1.28). Roflumilast significantly improved lung function relative to placebo, but not quality of life measures. AEs (RR 1.11; 95% CI 1.03-1.19) and discontinuations of treatment due to AEs (RR 1.63; 95% CI 1.45-1.84) were significantly more frequent with roflumilast than placebo. In the chronic obstructive pulmonary disease (COPD) Safety Pool (12,054 patients), the overall incidence of serious AEs did not differ between groups. However, atrial fibrillation (0.4% versus 0.2%; p = 0.02) and suicidality (0.08% versus 0%) were more frequent with roflumilast than placebo.

Conclusions: The efficacy of roflumilast appears modest compared with other available therapies for COPD. Further studies are needed to investigate the risk-benefit ratio and long-term safety of roflumilast before its wider use.