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

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; glycopyrronium; network meta-analysis; systematic review; tiotropium.

Figure 1

Flow diagram of study selection process. Note: Both a publication and CSR were available for the ATTAIN and ACCORD I study. Abbreviations: PICOS, population, intervention, comparators, outcomes, and study design; CSRs, clinical study reports; ACCORD, AClidinium in Chronic Obstructive Respiratory Disease COPD; ATTAIN, Aclidinium To Treat Airway obstruction IN COPD patients.

Figure 2

Network formed by interventions and their direct comparisons included in the analyses. Note: The GLOW2 trial compares glycopyrronium to tiotropium 18 μg and placebo and is therefore included three times in this figure. Abbreviations: GLOW, GLycopyrronium bromide in COPD airways clinical study; OD, once daily; BID, twice a day.

Figure 3

Forest plot of base case network meta-analysis results for aclidinium. Note: Difference in change from baseline (CFB), 95% credible intervals (95% Crl) and probability that aclidinium is better than the comparator at 12 weeks and 24 weeks. Abbreviations: AB400, aclidinium 400 μg twice daily; TI05, tiotropium 5 μg bromide once daily; TI018, tiotropium 18 μg bromide once daily; GLYC050, glycopyrronium 50 μg once daily; FEV, forced expiratory volume in 1 second; SGRQ, St George’s Respiratory Questionnaire; TDI, Transition Dyspnea Index.