Abstract
BackgroundIncreasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers.MethodsA systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA). The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted.ResultsThe analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09). Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models. Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included. These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients.ConclusionResults of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality. Further research is warranted to strengthen this conclusion.Electronic supplementary materialThe online version of this article (doi:10.1186/s12890-015-0138-4) contains supplementary material, which is available to authorized users.
Highlights
Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients
Systematic review A systematic review was conducted to identify randomised, blinded trials of COPD patients treated with tiotropium, beclomethasone, budesonide, fluticasone propionate, triamcinolone, bambuterol, formoterol, salmeterol, salbutamol, indacaterol, theophylline, roflumilast, indacaterol maleate, ipratropium bromide, vilanterol trifenatate, fluticasone furoate or placebo
Dosages of the same therapy were combined for the purposes of the analysis (indacaterol (150 μg od, 300 μg od, 600 μg od), budesonide (200 μg bid, 400 μg bid, 1200 μg od for 6 months followed by 800 μg od for 30 months), fluticasone propionate (250 μg bid, 500 μg bid), salmeterol (50 μg bid, 100 μg bid), formoterol (6 μg bid, 12 μg bid, μg bid) and salmeterol fluticasone propionate combination (SFC) (50/ 250 μg bid, 50/ 500 μg bid))
Summary
Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers. Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity across the world, and the third leading cause of death globally [1, 2]. Network meta-analysis (NMA) provides a statistical approach to combining direct and indirect trial evidence to generate relative treatment effects between different drugs on outcomes of interest. In the absence of headto-head trials including all comparators, NMA has been recommended by reimbursement agencies in the UK and Germany [6, 7] and endorsed by influential bodies such as ISPOR [8]. NMA has been applied to COPD mortality data on two previous occasions [9, 10].
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