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

Abstract

ObjectivesTo 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.MethodsSystematic 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.Results212 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.ConclusionFurther 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 numberCRD42018088013.

Efficacy and Safety of Budesonide/Glycopyrronium/Formoterol Fumarate versus Other Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis

“…In lieu of head-to-head evidence, network meta-analyses (NMA) comparing the efficacy of triple therapy as a class with LAMA/LABA dual therapy or bronchodilator monotherapy have previously been presented [ 9 – 11 ]. Additionally, pairwise meta-analyses have compared triple therapies with ICS/LABA [ 12 , 13 ] or LAMA/LABA therapies [ 13 ].…”

Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution

“…74,76,84 At this time, there are evidences derived about the effect of ICS-base treatments on mortality in COPD patients. 101,102 Along this line, note that a pooled post hoc analysis of the published clinical studies involving BDP/FF/G fixed combination was performed, demonstrating a reduction in fatal events in patients treated with ICScontaining medications, with a trend of statistical significance (hazard ratio = 0.72, 95% CI 0.50-1.02, p = 0.066), that becomes significant if we consider reduction in fatal events for non-respiratory reasons (hazard ratio = 0.65, 95% CI 0.43-0.97, p = 0.037). 103,104 In conclusion, a fixed combination of three drugs in a single inhaler can improve long-term adherence to the therapy, reducing the risk of exacerbations and hospital resources utilization.…”