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

Abstract

BackgroundRandomized, 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).MethodsA 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.ResultsTwenty-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.ConclusionThe new LAMAs studied had at least comparable efficacy to tiotropium, the established class standard. Choice should depend on physician’s and patient’s preference.

Genomic Characterization of Posttraumatic Stress Disorder in a Large US Military Veteran Sample

“…Our findings also suggest consideration of several other drug classes as therapeutic candidates for PTSD. For example, acetylcholine receptor antagonists could be considered given the convergence of (1) the PheWAS association via TRAIP with Chronic Obstructive Pulmonary Disease (COPD; which can be treated with muscarinic receptor antagonists (Ismaila et al, 2015)), and (2) their association in cMAP with PLEKHM1. Angiotensin receptor antagonists, also identified as drug candidates through cMAP, have a strong preclinical rationale for use in PTSD (Marvar et al, 2014;Shekhar, 2014) and are, in fact, currently undergoing testing in a randomized placebo-controlled trial of losartan for PTSD (ClinicalTrials.gov Identifier: NCT02709018P).…”

Pharmacoeconomic Analysis of Tiotropium Bromide and Olodaterol Fixed Combination as Maintenance Therapy in Patients with Chronic Obstructive Pulmonary Disease in Russian Federation

“…Кроме того, в других метаанализах сравнивалась эффективность отдельных компонентов комбинированных схем терапии. Так в сетевом метаанализе, выполненном Ismaila и др., 2015, показана сопоставимая клиническая эффективность ДДАХ тиотропия и гликопиррония в стандартных дозировках, и по заключению исследователей, выбор конкретного препарата должен зависеть только от предпочтений врача и пациента [11]. Сетевой метаанализ Disse и др., 2014 г. показал сравнимую эффективность олодатерола и индакатерола в стандартных дозировках, в том числе при наличии сопутствующей терапии ДДАХ [12].…”

Therapeutic Role of Tiotropium in Chronic Obstructive Airways Diseases

“…As well as the individual clinical trials, a number of systematic reviews with meta-regression analysis of pooled data have summarised the efficacy of tiotropium in patients with COPD 19,[28][29][30][31][32][33][34] as well as its safety 35,36 . This review will not duplicate these reviews but will highlight the main findings.…”

“…In a meta-analysis of these studies, aclidinium resulted in a significantly greater improvement in pre-dose FEV 1 than placebo with a mean difference of 0. 30 . The GLOW5 trial, a 12-week blinded, double-dummy study comparing glycopyrronium with tiotropium, showed no difference between the two LAMAs in their effect on trough FEV 1 , TDI and SGRQ 48 .…”