Olodaterol 2.5micrograms/dose solution for inhalation cartridge with device CFC free

BackgroundOnly few randomized controlled trials (RCTs) for head-to-head comparison have been conducted between various combinations of long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs). Our study was conducted to compare acute exacerbation and all-cause mortality among different LAMA/LABA regimens using Bayesian network meta-analysis (NMA).MethodsWe searched Medline, EMBASE, and the Cochrane library (search date: July 1, 2019). We included parallel-group RCTs comparing LAMA/LABA combinations with other inhaled drugs in the stable COPD for ≥ 48 weeks. Two different network geometries were used. The geometry of network (A) had nodes of individual drugs or their combination, while that of network (B) combined all other treatments except LAMA/LABA into each drug class. This study was prospectively registered in PROSPERO; CRD42019126753.ResultsWe included 16 RCTs involving a total of 39,065 patients with stable COPD. Six combinations of LAMA/LABA were identified: tiotropium/salmeterol, glycopyrrolate/indacaterol, umeclidinium/vilanterol, tiotropium/olodaterol, aclidinium/formoterol, and glycopyrrolate/formoterol. We found that umeclidinium/vilanterol was associated with a lower risk of total exacerbations than other LAMA/LABAs in the NMA using network (A) (level of evidence: low or moderate). However, the significant differences were not present in the NMA of network (B). There were no significant differences among the LAMA/LABA combinations in terms of the number of moderate to severe exacerbations, all-cause mortality, major adverse cardiovascular events, or pneumonia.ConclusionsThe present NMA including all available RCTs provided that there is no strong evidence suggesting different benefits among LAMA/LABAs in patients with stable COPD who have been followed up for 48 weeks or more.Trial registrationThis study was prospectively registered in PROSPERO; CRD42019126753.

Abstract licence: CC BY

Abstract Background: Combinations of long-acting bronchodilators with different mechanisms of action are recommended to improve prognosis and reduce risk of adverse events of chronic obstructive pulmonary disease (COPD). It is unclear whether the new combination therapy with long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) was superior to tiotropium alone. Methods: We measured the efficacy of the TIO/OLO combination vsTIO alone for COPD patients based on electronic databases up to February 2019. After rigorous quality review, data was extracted from eligible trials. All the main outcomes were pooled analysis using RevMan software. Results: A total of 6 randomized controlled trials (RCTs) were identified. The pooled results of our meta-analysis demonstrated that FEV1 [MD = 0.03, 95% CI (−0.01,0.07), P = .18], FVC [MD = -0.03, 95%CI (−0.06,0.00), P = .09] and FEV1%pred [MD = 0.35, 95%CI (−0.30, 0.99), P = .29] all showed no significant difference between the 2 groups. The overall incidence of adverse effects (AEs) [OR = 1.01,95%CI (0.93,1.09), P = .87] and serious AEs [OR = 1.04,95% CI (0.82, 1.32), P = .72] in the combination group was similar to that of the TIO alone group, without statistical significance. Conclusion: These studies reported that the TIO/OLO combination did not show superior effects than tiotropium alone for COPD. Additionally, both therapies were well tolerated.

Abstract licence: CC BY-NC 4.0

ObjectivesTo evaluate the effects of tiotropium/olodaterol (T/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized 129Xe MRI measures.Materials and methodsRetrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5 ± 7.7 years; 17 men); 30 completed the MRI extension at 1.5 T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman's rank and bootstrap 95% confidence intervals (95% CIs).ResultsPREFUL parameters improved after T/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (p 129Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (ρ = 0.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and ¹²⁹Xe-derived VDP, apparent diffusion coefficient, and compartment ratios.ConclusionPREFUL MRI sensitively captured immediate SD T/O-induced improvements in V/Q parameters and dose-dependent PWV responses after sustained bronchodilation.Key pointsQuestion Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium/olodaterol on ventilation-perfusion and vascular function in COPD patients? Findings Tiotropium/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing. Clinical relevance PREFUL MRI detected immediate and sustained functional improvements after tiotropium/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized ¹²⁹Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.

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BackgroundChronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in patients with chronic heart failure (CHF). A growing number of patients are suffering from both COPD and CHF, and these conditions worsen each other. Inhaled bronchodilator therapy with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) in combination is currently the mainstay of treatment for COPD. However, the effect of LAMA/LABA on HF with COPD remains unknown.Methods and resultsThe COPD-HF trial is a multicenter, double-arm, open-label, exploratory, investigator-initiated clinical study to investigate the effect of LAMA/LABA on HF in patients suffering from both COPD and CHF. The participants are randomly assigned (1 : 1) to the LAMA/LABA (tiotropium+olodaterol FDC (fixed-dose combination) 5/5 ug) group (once a day, 2 inhalations) or non-pharmacological treatments for COPD as a control group. The planned number of patients to be enrolled in this trial is 54 in total (27 in each group). The participants are followed up for 12 weeks with and without LAMA/LABA. The primary endpoint is the change in plasma B-type natriuretic peptide levels from the baseline to the end of this study (12 weeks).ConclusionsThe COPD-HF trial will investigate the efficacy of LAMA/LABA on HF in patients with COPD and CHF.

Abstract licence: CC BY-NC-ND

Neil S Roskell,1 Antonio Anzueto,2 Alan Hamilton,3 Bernd Disse,4 Karin Becker5 1Statistics, Bresmed Health Solutions Ltd, Sheffield, UK; 2School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA; 3Medical Department, Boehringer Ingelheim (Canada) Ltd, Burlington, ON, Canada; 4Medical Department, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany; 5Global Health Economics and Outcomes Research, Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany Purpose: In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted. Methods: A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, St George’s Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations. Results: Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol). Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters), the following mean differences (95% confidence interval) were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, –0.005 (–0.077 to 0.067), and indacaterol 150 mcg versus olodaterol 5 mcg, 0.020 (–0.036 to 0.077); trials with concomitant tiotropium: indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (–0.043 to 0.042). In sensitivity analyses of the full network, results for change from baseline in trough FEV1 favored indacaterol, but this dataset suffered from trial design heterogeneity. For the other endpoints investigated, no statistically significant differences were found when analyzed in the full network. Conclusion: When compared under similar trial conditions, olodaterol and indacaterol have similar efficacy in patients with COPD. This research highlights the importance of considering the concomitant COPD medication when evaluating treatment effects in COPD. Keywords: COPD, olodaterol, indacaterol, meta-analysis, systematic review, LABA

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