title: Efficiency and safety of roflumilast combined with long-acting bronchodilators on moderate-to-severe stable chronic obstructive pulmonary disease patients: a meta-analysis.
abstract: BACKGROUND
  Roflumilast, a phosphodiesterase-4 inhibitor recommended by clinical guideline, is always being used in combination with at least one long-acting bronchodilator in patients with stable chronic obstructive pulmonary disease (COPD). However, there are few evidences about whether the combination of roflumilast and long-acting bronchodilators is safer and more effective in patients with moderate-to-very severe stable COPD. In our study, we investigate the effect and safety of roflumilast combined with long-acting bronchodilators on moderate-to-severe stable COPD patients.
  
  
  METHODS
  Several databases were adopted in February 5th 2016, so as to identify relevant randomized controlled trial (RCT). Studies indicated that the patients in the experimental group had to receive roflumilast and concomitant treatment with long-acting bronchodilators, and the patients in the control group had to receive placebo and concomitant treatment with long-acting bronchodilators. The primary outcome was COPD exacerbations and the secondary outcome was adverse events. The relative risks (RRs) and 95% confidence intervals (CIs) were calculated.
  
  
  RESULTS
  Total 5,746 patients were involved in all six trials. Roflumilast combined with long-acting bronchodilators could lead to significant reduction in exacerbations of COPD (RR, 0.77; 95% CI, 0.69 to 0.86; P<0.00001; I2=0%), and cause some adverse events such as: back pains, headache, diarrhea, nausea, weight loss, insomnia and decreased appetite. According to the subgroup analysis, the test for finding subgroup difference between roflumilast combined with long-acting bronchodilators and roflumilast combined with ICS and long-acting bronchodilators showed no significance in reducing exacerbations.
  
  
  CONCLUSIONS
  Roflumilast combined with long-acting bronchodilators is a better option for moderate-to-severe COPD patients than exclusive use of long-acting bronchodilators in reducing exacerbations. However, it can cause some side effects. Further study needs consider well enough of the benefits and adverse events caused by roflumilast combined with long-acting bronchodilators.
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Yitai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Respiratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
keywords: Meta-analysis; chronic obstructive pulmonary disease (COPD); exacerbations; long-acting bronchodilators