Potential treatment benefits and safety of roflumilast in COPD: a systematic review and meta-analysis

Abstract

Background: Current evidence suggests that roflumilast is efficacious in treating COPD, especially in preventing the acute exacerbation of COPD.

Objectives: This study was designed to evaluate the clinical effects and safety of roflumilast in the treatment of stable COPD using randomized clinical trial (RCT) data.

Methods: A MEDLINE, EMBASE, and Cochrane Controlled Trials Register search was carried out. RCTs reporting the treatment effects of roflumilast in COPD were identified. Relevant data were extracted and a meta-analysis was performed.

Results: A total of nine articles and 13 RCT studies were identified. Overall, 29.1% of the subjects in the roflumilast group showed evidence of exacerbation. The corresponding figure was 32.2% in the placebo group. According to pooled analysis, the use of roflumilast reduced COPD exacerbations in comparison to placebo (odds ratio [OR] =0.82, 95% confidence interval [CI] =0.75-0.9). The quality of life and spirometry were improved. For patients receiving baseline pre-bronchodilators, their average forced expiratory volume in the first second showed evidence of change when they took roflumilast (64.88 mL; 95% CI =54.09-75.66). Those who took placebo showed no evidence of change. Similar result was observed in patients receiving baseline (54.49 mL; 95% CI =44.04-64.94). As for the safety of roflumilast treatment, the overall cumulative incidence of adverse drug reaction was 54.2% in the roflumilast group and 48.2% in the placebo group (OR =1.36, 95% CI =1.13-1.65). The adverse effects included diarrhea, headache, nausea, weight loss, and insomnia.

Conclusion: The efficacy of roflumilast in the prevention of acute exacerbation of COPD is obvious. Roflumilast is proved to be able to improve spirometry of COPD patients. The adverse drug reaction did not increase significantly in the roflumilast group compared with the control group. COPD patients can benefit from roflumilast therapy. However, our results are limited by the cohort design of the selected studies and the degree of heterogeneity among them; hence, more randomized trials are needed to further support this conclusion.

Keywords: COPD; adverse drug reaction; efficacy; meta-analysis; roflumilast; spirometry.

Figure 1

Flowchart for identification of studies included in the meta-analysis. Abbreviation: RCT, randomized clinical trial.

Figure 2

Pooled OR for COPD-related exacerbations (with 95% CI) of eligible studies comparing roflumilast with placebo. Note: Items in brackets in the Study column are code names within the trial. Abbreviations: OR, odds ratio; CI, confidence interval; M–H, Mantel–Haenszel; H, high; L, low.

Figure 3

Pooled mean change of FEV₁ from baseline prebronchodilator (with 95% CI) of eligible studies comparing roflumilast with placebo. Note: Items in brackets in the Study column are code names within the trial. Abbreviations: FEV₁, forced expiratory volume in the first second; CI, confidence interval; Std, standard; IV, instrumental variable; H, high; L, low; SD, standard deviation.

Figure 4

Pooled mean change of FEV₁ from baseline postbronchodilator (with 95% CI) of eligible studies comparing roflumilast with placebo. Note: Items in brackets in the Study column are code names within the trial. Abbreviations: FEV₁, forced expiratory volume in the first second; CI, confidence interval; IV, instrumental variable; H, high; L, low; SD, standard deviation.

Figure 5

Pooled OR for adverse event (with 95% CI) of eligible studies comparing roflumilast with placebo. Note: Items in brackets in the Study column are code names within the trial. Abbreviations: OR, odds ratio; CI, confidence interval; M–H, Mantel–Haenszel; H, high; L, low.