Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis
Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis
Blog Article
Afisi Segun Ismaila,1,2 Eline L Huisman,3 Yogesh Suresh Punekar,4 Andreas Karabis31Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA; 2Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada; 3Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands; 4Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UKBackground: 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]; boots 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.Conclusion: 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.Keywords: anticholinergics, templar muscarinic antagonist, bronchodilator, systematic review, meta-analysis.