Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD: a systematic review and network meta-analysis

• Published in: International journal of chronic obstructive pulmonary disease Vol. 10; no. Issue 1; pp. 2495 - 2517
• Main Authors: Ismaila, Afisi Segun, Huisman, Eline L, Punekar, Yogesh Suresh, Karabis, Andreas
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01-01-2015; Dove Medical Press Ltd; Dove Medical Press
• Subjects: Aged; Bayes Theorem; Bias; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - adverse effects; Care and treatment; Clinical trials; Dosage and administration; Drug Administration Schedule; Dyspnea; Female; Forced Expiratory Volume; Generalized linear models; Glycopyrrolate - administration & dosage; Humans; Literature reviews; Lung - drug effects; Lung - physiopathology; Lung diseases, Obstructive; Male; Meta-analysis; Middle Aged; Muscarinic antagonists; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - adverse effects; Original Research; Patients; Pulmonary Disease, Chronic Obstructive - diagnosis; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Quinuclidines - administration & dosage; Randomized Controlled Trials as Topic; Recovery of Function; Safety and security measures; Spirometry; Surveys and Questionnaires; Systematic review; Time Factors; Tiotropium; Tiotropium Bromide - administration & dosage; Treatment Outcome; Tropanes - administration & dosage; meta-analysis; systematic review; muscarinic antagonist; anticholinergics; bronchodilator
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S92412

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).
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.
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]; 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.
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.