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

Objective To investigate the efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease (COPD). Methods PubMed, EMBASE, CINAHL, Cochrane clinical trials database, ScienceDirect, Chinese biomedical literature database, Wanfang, Weipu database, and Chinese periodical database were searched for articles about Phase Ⅱ/Ⅲ clinical trials in patients with COPD treated with roflumilast, published from January 1995 to July 2014. The parameters of lung function, the aggravated risk of COPD, the health-related quality of life and the adverse effects were evaluated. The Jadad scale and the Cochrane collaboration's tool for assessing risk of bias were respectively used for evaluating the RCTs. Meta-analysis was performed using an inverse-variance model, providing weighted mean difference (WMD) and 95% confidence intervals (CI). Heterogeneity was determined by I2 statistic. Results A total of 7 eligible studies were identified, including 9 randomized controlled trials. The forced expiratory volume in one second (WMD=57.56, 95%CI: 48.03~67.10, Z=11.83; WMD=63.97, 95%CI: 54.01~73.92, Z=12.60, all P<0.05), forced vital capacity (WMD=86.8, 95%CI: 66.00~107.60, Z=8.18; WMD=89.63, 95%CI: 70.50~108.77, Z=9.18, all P<0.05) and forced expiratory flow between 25% and 75% of vital capacity (WMD=21.26, 95%CI: 11.50~31.03, Z=4.27; WMD=23.04, 95%CI: 14.17~31.91, Z=5.09, all P<0.05) before and after bronchodilator increased in the roflumilast group, respectively. The overall exacerbation rate (OR=-0.16, 95%CI: -0.24~-0.08, Z=3.74, P<0.05) and the moderate exacerbation rate (OR=-0.08, 95%CI: -0.15~-0.02, Z=2.43, P=0.02) were reduced, the time to first moderate-severe exacerbation were prolonged (WMD=9.65, 95%CI: 5.31~13.98, Z=4.30, P<0.05), transition dyspnea index significantly increased (WMD=0.3, 95%CI: 0.16~0.44, Z=4.24, P<0.05) in patients treated with roflumilast, while no statistical differences were noted in severe exacerbation rate (OR=0.00, 95%CI: -0.02~0.02, Z=0.40, P=0.69) and the time to second moderate-severe exacerbation (WMD=28.24, 95%CI: -2.13~58.62, Z=1.82, P=0.07). The adverse effects related to treatment are mainly involved in the digestive system and nervous system, mainly occurred during the first 4 weeks after treatment and existed self-limited up to down course. Conclusion As a novel anti-inflammatory drug, roflumilast is likely to treat the patients with stable COPD. Key words: Pulmonary disease, chronic obstructive; Roflumilast; Treatment outcome; Safety; Meta-analysis