title: Efficacy and Safety of Aclidinium/Formoterol versus Tiotropium in COPD: Results of an Indirect Treatment Comparison.
abstract: BACKGROUND
  The objective of this study was to estimate the relative efficacy and safety of fixed-dose combination aclidinium/formoterol 400/12 μg twice daily compared to tiotropium 18 μg once daily in adult patients with moderate-to-severe chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  A systematic literature review performed in March 2014, using a predefined search strategy in MEDLINE, EMBASE and Cochrane Library, identified 17 randomized placebo-controlled trials, (tiotropium n = 15; aclidinium/formoterol n = 2). Outcomes of interest were: bronchodilation (peak and trough forced expiratory volume in 1 s (FEV1)), COPD symptoms [Transition Dyspnea Index (TDI) focal score and % of responders (>1 unit improvement)] and Health Related Quality of Life (HRQoL) [St. George's Respiratory Questionnaire (SGRQ) total score and % responders (>4 unit improvement)], % of patients with ≥1 exacerbations, adverse events (AE), serious adverse events (SAE), hospitalization and mortality, all at 24 weeks. In the absence of head-to-head trials between aclidinium/formoterol and tiotropium, a Bayesian indirect treatment comparison (ITC) was used with placebo as common control.
  
  
  RESULTS
  Regarding bronchodilation, aclidinium/formoterol was found to be more efficacious than tiotropium at peak FEV1, with mean difference in change from baseline (DCFB) 143 mL [95% credible interval (CrI): 112, 174] and at trough FEV1 [DCFB 26 mL (95% CrI -2, 55)]. Aclidinium/formoterol is expected to be more efficacious than tiotropium in improving dyspnea symptoms measured by TDI [DCFB 0.54 points (95% CrI 0.09, 0.99); odds ratio (OR) of responders 1.51 (95% CrI 1.11, 2.06)]. SGRQ results are comparable for aclidinium/formoterol versus tiotropium [DCFB -0.52 (95% CrI -2.21, 1.17); OR of responders 1.16 (95% CrI 0.47, 2.87)]. The ITC results suggest similar safety profiles regarding AEs, SAEs and hospitalization.
  
  
  CONCLUSIONS
  Based on the ITC, aclidinium/formoterol is expected to be more efficacious than tiotropium in terms of lung function and symptom control while providing comparable HRQoL results and safety profile.
  
  
  BACKGROUND
  AstraZeneca.
authors.affiliation: Real World Strategy and Analytics, Mapi Group, Houten, The Netherlands.
authors.forename: Goran
authors.initials: G
authors.lastname: Medic
authors.affiliation: AstraZeneca, Barcelona, Spain.
authors.forename: Leandro
authors.initials: L
authors.lastname: Lindner
authors.affiliation: Real World Strategy and Analytics, Mapi Group, Houten, The Netherlands. mvanderweijden@mapigroup.com.
authors.forename: Miriam
authors.initials: M
authors.lastname: van der Weijden
authors.affiliation: Real World Strategy and Analytics, Mapi Group, Houten, The Netherlands.
authors.forename: Andreas
authors.initials: A
authors.lastname: Karabis
mesh_terms: D001499:Bayes Theorem; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D004417:Dyspnea / Q000503:physiopathology; D005541:Forced Expiratory Volume; D000068759:Formoterol Fumarate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D016017:Odds Ratio; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D012720:Severity of Illness Index; D000069447:Tiotropium Bromide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014326:Tropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001993:Bronchodilator Agents; D004338:Drug Combinations; D014326:Tropanes; C542859:aclidinium bromide; D000068759:Formoterol Fumarate; D000069447:Tiotropium Bromide
keywords: Aclidinium; Formoterol; Indirect treatment comparison; Literature review; Tiotropium