title: Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis.
abstract: BACKGROUND
  Randomized, controlled trials comparing long-acting muscarinic antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA) assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium 62.5 µg OD).
  
  
  METHODS
  A systematic literature review identified randomized, controlled trials of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework examined change from baseline in trough forced expiratory volume in 1 second (FEV1), transitional dyspnea index focal score, St George's Respiratory Questionnaire score, and rescue medication use.
  
  
  RESULTS
  Twenty-four studies (n=21,311) compared LAMAs with placebo/each other. Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively, demonstrated favorable results versus placebo, for change from baseline (95% credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL [77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL [104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL [123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St George's Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to -2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]); 24-week transitional dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00 [0.49-1.51]); and 24-week rescue medication use (data not available; -0.41 puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0.74 to -0.30]; -0.30 puffs/day [-0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline (95% credible interval) were -12.8 mL (-39.39 to 13.93), aclidinium versus tiotropium; 3.08 mL (-7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL (-11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (-11.60 to 43.15), glycopyrronium versus aclidinium; 35.40 mL (-5.06 to 76.07), umeclidinium versus aclidinium; and 19.50 mL (-15.30 to 54.38), umeclidinium versus glycopyrronium. Limitations included inhaler-related factors and safety; longer-term outcomes were not considered.
  
  
  CONCLUSIONS
  The new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard. Choice should depend on physician's and patient's preference.
authors.affiliation: Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA ; Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
authors.forename: Afisi Segun
authors.initials: AS
authors.lastname: Ismaila
authors.affiliation: Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands.
authors.forename: Eline L
authors.initials: EL
authors.lastname: Huisman
authors.affiliation: Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK.
authors.forename: Yogesh Suresh
authors.initials: YS
authors.lastname: Punekar
authors.affiliation: Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands.
authors.forename: Andreas
authors.initials: A
authors.lastname: Karabis
mesh_terms: D000368:Aged; D001499:Bayes Theorem; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume; D006024:Glycopyrrolate / Q000008:administration & dosage; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D011812:Quinuclidines / Q000008:administration & dosage; D016032:Randomized Controlled Trials as Topic; D020127:Recovery of Function; D013147:Spirometry; D011795:Surveys and Questionnaires; D013997:Time Factors; D000069447:Tiotropium Bromide / Q000008:administration & dosage; D016896:Treatment Outcome; D014326:Tropanes / Q000008:administration & dosage
chemical_list: D001993:Bronchodilator Agents; C573971:GSK573719; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D014326:Tropanes; C542859:aclidinium bromide; D006024:Glycopyrrolate; D000069447:Tiotropium Bromide
keywords: anticholinergics; bronchodilator; meta-analysis; muscarinic antagonist; systematic review