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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

ABSTRACT: OBJECTIVES:To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses. METHODS:Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ?20 weeks of treatment; short-term: <20 weeks), lung function (?12 weeks), health-related quality of life, mortality and adverse events. Qualitative comparisons of efficacies between RCTs and observational studies. RESULTS:212 RCTs and 19 observational studies were included. Compared with combined long-acting beta-adrenoceptor agonists and long-acting muscarinic antagonists (LABA+LAMA), triple therapy (LABA+LAMA+inhaled corticosteroid) was significantly more effective at reducing exacerbations (long-term 0.85 (95% CI: 0.78 to 0.94; short-term 0.67 (95% CI: 0.49 to 0.92)) and mortality (0.72 (95% CI: 0.59 to 0.89)) but was also associated with increased pneumonia (1.35 (95% CI: 1.10 to 1.67)). No differences in lung function (0.02 (95% CI: -0.10 to 0.14)), health-related quality of life (-1.12 (95% CI: -3.83 to 1.59)) or other adverse events (1.02 (95% CI: 0.96 to 1.08)) were found. Most of the observational evidence trended in the same direction as pooled RCT data. CONCLUSION:Further evidence, especially pragmatic trials, are needed to fully understand the characteristics of patient subgroups who may benefit from triple therapy and for those whom the extra risk of adverse events, such as pneumonia, may outweigh any benefits. PROSPERO REGISTRATION NUMBER:CRD42018088013.

SUBMITTER: Axson EL

PROVIDER: S-EPMC7526304 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

Axson Eleanor L EL Lewis Adam A Potts James J Pang Marie M Dickinson Scott S Vioix Helene H Quint Jennifer K JK

BMJ open 20200929 9

<h4>Objectives</h4>To integrate evidence from randomised controlled trials (RCTs) and observational studies on the efficacy of inhaled treatments for chronic obstructive pulmonary disease using network meta-analyses.<h4>Methods</h4>Systematic searches MEDLINE and Embase based on predetermined criteria. Network meta-analyses of RCTs investigated efficacy on exacerbations (long-term: ≥20 weeks of treatment; short-term: <20 weeks), lung function (≥12 weeks), health-related quality of life, mortalit ...[more]

PMID: 32994234

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Project description:BACKGROUND:Although exacerbation and mortality are the most important clinical outcomes of stable chronic obstructive pulmonary disease (COPD), the drug classes that are the most efficacious in reducing exacerbation and mortality among all possible inhaled drugs have not been determined. METHODS AND FINDINGS:We performed a systematic review (SR) and Bayesian network meta-analysis (NMA). We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the European Union Clinical Trials Register, and the official websites of pharmaceutical companies (from inception to July 9, 2019). The eligibility criteria were as follows: (1) parallel-design randomized controlled trials (RCTs); (2) adults with stable COPD; (3) comparisons among long-acting muscarinic antagonists (LAMAs), long-acting beta-agonists (LABAs), inhaled corticosteroids (ICSs), combined treatment (ICS/LAMA/LABA, LAMA/LABA, or ICS/LABA), or a placebo; and (4) study duration ? 12 weeks. This study was prospectively registered in International Prospective Register of Systematic Reviews (PROSPERO; CRD42017069087). In total, 219 trials involving 228,710 patients were included. Compared with placebo, all drug classes significantly reduced the total exacerbations and moderate to severe exacerbations. ICS/LAMA/LABA was the most efficacious treatment for reducing the exacerbation risk (odds ratio [OR] = 0.57; 95% credible interval [CrI] 0.50-0.64; posterior probability of OR > 1 [P(OR > 1)] < 0.001). In addition, in contrast to the other drug classes, ICS/LAMA/LABA and ICS/LABA were associated with a significantly higher probability of reducing mortality than placebo (OR = 0.74, 95% CrI 0.59-0.93, P[OR > 1] = 0.004; and OR = 0.86, 95% CrI 0.76-0.98, P[OR > 1] = 0.015, respectively). The results minimally changed, even in various sensitivity and covariate-adjusted meta-regression analyses. ICS/LAMA/LABA tended to lower the risk of cardiovascular mortality but did not show significant results. ICS/LAMA/LABA increased the probability of pneumonia (OR for triple therapy = 1.56; 95% CrI 1.19-2.03; P[OR > 1] = 1.000). The main limitation is that there were few RCTs including only less symptomatic patients or patients at a low risk. CONCLUSIONS:These findings suggest that triple therapy can potentially be the best option for stable COPD patients in terms of reducing exacerbation and all-cause mortality.

Project description:OBJECTIVE:To compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD). DESIGN:Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES:PubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018. ELIGIBILITY CRITERIA:Randomised controlled trials comparing triple therapy with dual therapy or monotherapy in patients with COPD were eligible. Efficacy and safety outcomes of interest were also available. DATA EXTRACTION AND SYNTHESIS:Data were collected independently. Meta-analyses were conducted to calculate rate ratios, hazard ratios, risk ratios, and mean differences with 95% confidence intervals. Quality of evidence was summarised in accordance with GRADE methodology (grading of recommendations assessment, development, and evaluation). RESULTS:21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting ? agonist (LABA), and inhaled corticosteroid (ICS). Triple therapy was associated with a significantly reduced rate of moderate or severe exacerbations compared with LAMA monotherapy (rate ratio 0.71, 95% confidence interval 0.60 to 0.85), LAMA and LABA (0.78, 0.70 to 0.88), and ICS and LABA (0.77, 0.66 to 0.91). Trough forced expiratory volume in 1 second (FEV1) and quality of life were favourable with triple therapy. The overall safety profile of triple therapy is reassuring, but pneumonia was significantly higher with triple therapy than with dual therapy of LAMA and LABA (relative risk 1.53, 95% confidence interval 1.25 to 1.87). CONCLUSIONS:Use of triple therapy resulted in a lower rate of moderate or severe exacerbations of COPD, better lung function, and better health related quality of life than dual therapy or monotherapy in patients with advanced COPD. STUDY REGISTRATION:Prospero CRD42018077033.

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

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Inhaled therapies for chronic obstructive pulmonary disease: a systematic review and meta-analysis.

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