Triple therapy in the management of chronic obstructive pulmonary disease: systematic review and meta-analysis

• Published in: BMJ (Online) Vol. 363; p. k4388
• Main Authors: Zheng, Yayuan, Zhu, Jianhong, Liu, Yuyu, Lai, Weiguang, Lin, Chunyu, Qiu, Kaifen, Wu, Junyan, Yao, Weimin
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 06.11.2018; BMJ Publishing Group LTD; BMJ Publishing Group Ltd
• Subjects: Acetylcholine receptors (muscarinic); Adrenal Cortex Hormones - therapeutic use; Adrenergic beta-2 Receptor Agonists - therapeutic use; Bias; Bronchodilator Agents - therapeutic use; Chronic obstructive pulmonary disease; Clinical trials; Confidence intervals; Corticosteroids; Drug therapy; Drug Therapy, Combination; Evidence-based medicine; Forced Expiratory Volume; Humans; Lung diseases; Meta-analysis; Muscarinic Antagonists - therapeutic use; Obstructive lung disease; Patients; Pneumonia; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Quality of Life; Respiratory function; Systematic review
• ISSN: 0959-8138; 1756-1833; 1756-1833
• DOI: 10.1136/bmj.k4388

AbstractObjectiveTo compare the rate of moderate to severe exacerbations between triple therapy and dual therapy or monotherapy in patients with chronic obstructive pulmonary disease (COPD).DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesPubMed, Embase, Cochrane databases, and clinical trial registries searched from inception to April 2018.Eligibility criteriaRandomised 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 synthesisData 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).Results21 trials (19 publications) were included. Triple therapy consisted of a long acting muscarinic antagonist (LAMA), long acting β 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).ConclusionsUse 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 registrationProspero CRD42018077033.