Comparative efficacy of aclidinium versus glycopyrronium and tiotropium, as maintenance treatment of moderate to severe COPD patients: a systematic review and network meta-analysis

Abstract

Andreas Karabis,1 Leandro Lindner,2 Michelle Mocarski,3 Eline Huisman,1 Andrew Greening4 1MAPI Consultancy, AX Houten, The Netherlands; 2Almirall SA, Barcelona, Spain; 3Health Economics and Outcomes Research, Forest Research Institute, Jersey City, NJ, USA; 4University of Edinburgh, Lothian University Hospitals' Division, Edinburgh, UK Background: Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA) indicated for maintenance bronchodilator treatment of chronic obstructive pulmonary disease (COPD). The efficacy of aclidinium was compared with tiotropium and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled trials (RCTs) in moderate-to-severe COPD patients. Methods: A systematic review was performed to identify RCTs evaluating aclidinium 400 µg twice daily (BID), glycopyrronium 50 µg once daily (OD), tiotropium 18 µg OD, or tiotropium 5 µg OD in adults with moderate-to-severe COPD. The outcomes of interest were: trough forced expiratory volume in 1 second (FEV1); St George's Respiratory Questionnaire (SGRQ) total score and proportion of patients achieving ≥4 unit change; Transition Dyspnea Index (TDI) focal score and proportion of patients achieving ≥1 point change. The results were synthesized by means of a Bayesian NMA. Results: Twenty-one studies (22,542 patients) were included: aclidinium 400 µg BID (three studies); tiotropium 5 µg OD (three studies); tiotropium 18 µg OD (13 studies); and glycopyrronium 50 µg OD (two studies). Regarding trough FEV1 at 24 weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 µg (difference in change from baseline [CFB]), (0.02 L [95% credible interval CrI −0.05, 0.09]); tiotropium 18 µg (0.02 L [95% CrI −0.05, 0.08]); and glycopyrronium (0.00 L [95% CrI −0.07, 0.07]). Aclidinium resulted in higher improvement in SGRQ score at 24 weeks, compared to tiotropium 5 µg (difference in CFB, −2.44 [95% CrI −4.82, −0.05]); and comparable results to tiotropium 18 µg (−1.80 [95% CrI −4.52, 0.14]) and glycopyrronium (−1.52 [95% CrI −4.08, 1.03]). Improvements in TDI score were comparable for all treatments. Conclusion: Maintenance treatment with aclidinium 400 µg BID is expected to produce similar improvements in lung function, health-related quality of life, and dyspnea compared to tiotropium 5 µg OD; tiotropium 18 µg OD; and glycopyrronium 50 µg OD. Keywords: COPD, aclidinium, tiotropium, glycopyrronium, systematic review, network meta-analysis