title: The efficacy and safety of triple inhaled treatment in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis using Bayesian methods.
abstract: OBJECTIVE
  Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting β-agonists are frequently prescribed together, the efficacy of "triple therapy" has not been scientifically demonstrated. We conducted a systematic review and meta-analysis using Bayesian methods to compare triple therapy and TIO monotherapy.
  
  
  METHODS
  We searched the MEDLINE, EMBASE, and Cochrane Library databases for randomized controlled trials comparing the efficacy and safety of triple therapy and TIO monotherapy in patients with chronic obstructive pulmonary disease (COPD). We conducted a meta-analysis to compare the effectiveness and safety of triple therapy and TIO monotherapy using Bayesian random effects models.
  
  
  RESULTS
  Seven trials were included, and the risk of bias in the majority of the studies was acceptable. There were no statistically significant differences in the incidence of death and acute exacerbation of disease in the triple therapy and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible interval [CrI], 45.29-82.73), and patients receiving triple therapy showed more improvement in St George Respiratory Questionnaire scores (MD, -3.11 points; 95% CrI, -6.00 to -0.80) than patients receiving TIO monotherapy. However, both of these differences were lower than the minimal clinically important difference (MCID). No excessive adverse effects were reported in triple therapy group.
  
  
  CONCLUSIONS
  Triple therapy with TIO and ICSs/long-acting β-agonists was only slightly more efficacious than TIO monotherapy in treating patients with COPD. Further investigations into the efficacy of new inhaled drugs are needed.
authors.affiliation: Department of Internal Medicine, Healthcare Research Institute, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Kwak
authors.affiliation: Department of Statistics, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Information Statistics, Andong National University, Andong, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: Department of Preventive Medicine, College of Medicine, Korea University, Seoul, Republic of Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D001499:Bayes Theorem; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D004338:Drug Combinations; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D016017:Odds Ratio; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D020127:Recovery of Function; D011795:Surveys and Questionnaires; D000069447:Tiotropium Bromide / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D018680:Cholinergic Antagonists; D004338:Drug Combinations; D000069447:Tiotropium Bromide
keywords: chronic obstructive pulmonary disease (COPD); inhaled corticosteroids (ICSs); inhaled long-acting muscarinic antagonists (LAMAs); inhaled long-acting β2-agonists (LABAs)