Comparative efficacy of combination bronchodilator therapies in COPD: a network meta-analysis

Abstract

Background: Several new fixed-dose combination bronchodilators have been recently launched, and assessing their efficacy relative to each other, and with open dual combinations is desirable. This network meta-analysis (NMA) assessed the efficacy of umeclidinium and vilanterol (UMEC/VI) with that of available dual bronchodilators in single/separate inhalers.

Methods: A systematic literature review identified randomized controlled trials of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years), assessing the efficacy of combination bronchodilators in single or separate inhalers. Comparative assessment was conducted on change from baseline in trough forced expiratory volume in 1 second (FEV1), St George's Respiratory Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores, and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian framework.

Results: A systematic literature review identified 77 articles of 26 trials comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA showed that at 24 weeks, efficacy of UMEC/VI was not significantly different compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: -14.2, 42.3]), SGRQ total score (0.18 [-1.28, 1.63]), TDI focal score (-0.30 [-0.73, 0.13]), and rescue medication use (0.02 [-0.27, 0.32]); compared with salmeterol plus TIO on trough FEV1 (67.4 mL [-25.3, 159.4]), SGRQ total score (-0.11 [-1.84, 1.61]), and TDI focal score (0.58 [-0.33, 1.50]); and compared with formoterol plus TIO 18 μg on SGRQ total score (-0.68 [-1.77, 0.39]). Results at week 12 were consistent with week 24 outcomes. Due to lack of availability of evidence, no comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.

Conclusion: UMEC/VI has comparable efficacy to other dual-bronchodilator combinations on available efficacy endpoints.

Keywords: LABA/LAMA; QVA149; UMEC/VI; fomoterol; glycopyrronium; indacaterol; tiotropium; umeclidinium.

Figure 1

Summary of study-flow (A) registries (B) study selection. Abbreviations: CDSR, Cochrane Database of Systematic Review; CSR, clinical study report; DARE, Database of Abstracts of Reviews of Effects; EMBASE, Excerpta Medica dataBASE; EU-CTR, European Union Clinical Trials Register; HTA, Health Technology Assessment Database; GSK, GlaxoSmithKline; MEDLINE, Medical Literature Analysis and Retrieval System Online; NMA, network meta-analysis; PROSPERO, international prospective register of systematic review; WHO ICTRP, World Health Organization International Clinical Trials Registry Platform.

Figure 2

Overall network of studies in the NMA analysis of UMEC/VI versus LABA/LAMA combination therapies evaluated at 24 weeks for (A) trough FEV₁, (B) SGRQ total score, (C) TDI focal score, and (D) rescue medication use. Notes: Studies in bold represent those that report only mean values without reporting SE, SD, and 95% CI. Studies DB2113360 and DB2113374 from Decramer et al. Study DB2113373 from Donohue et al. Study ZEP117115 from Maleki-Yazdi et al. Abbreviations: CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FOR, formoterol; LABA, long-acting β2-agonist; LAMA, long-acting muscarinic antagonist; NMA, network meta-analysis; PBO, placebo; QVA149, indacaterol/glycopyrronium; SAL, salmeterol; SD, standard deviation; SE, standard error; SGRQ, St George’s Respiratory Questionnaire; TDI, transitional dyspnoea index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

Figure 3

Forest plot for (A) mean trough FEV₁, (B) mean SGRQ total scores, (C) mean TDI focal scores, and (D) mean rescue medication use of UMEC 55 μg/VI 22 μg versus comparators at 24 weeks. Notes: Dotted lines included in panels (A–C) indicate the MCIDs versus placebo if these have been defined: these have been included in the graph for reference purpose only. The values shown on the right of each figure represent mean (95% CI). Abbreviations: CFB, change from baseline; FEV₁, forced expiratory volume in 1 second; FOR, formoterol; MCID, minimal clinically important difference; PBO, placebo; QVA149, indacaterol/glycopyrronium; SAL, salmeterol; SGRQ, St George’s Respiratory Questionnaire; TDI, transitional dyspnea index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.