Efficacy and Safety of Single Inhaler Triple Therapy Versus Separate Triple Therapy in Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis

Purpose: This study aimed to compare the efficacy and safety of single inhaler triple therapy and separate triple therapy in the treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD). Methods: PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases were searched, and the search date was set from database inception until February 15, 2022. Randomized controlled trials of single inhaler triple therapy versus separate triple therapy, from which the results related to efficacy and safety profiles were extracted, and the methodologic quality and risk of bias were evaluated. Findings: Five published articles (6 clinical trials) were screened from 3437 articles with a total of 4075 patients receiving single inhaler triple therapy and 3533 patients receiving separate triple therapy. Compared with separate triple therapy, single inhaler triple therapy significantly increased the change in forced expiratory volume in 1 second from baseline (mean difference = 0.02 L; 95% CI, 0.00-0.05L; P < 0.01), and there was a statistical difference between the 2 groups. No significant difference was found between the single inhaler triple therapy and separate triple therapy groups in terms of moderate to severe exacerbation rate (relative risk [RR] = 0.97; 95% CI, 0.85-1.10; P = 0.63), the change in St. George's Respiratory Questionnaire from baseline (mean difference = 0.34; 95% CI, −0.88 to 1.57; P = 0.58), proportion of St. George's Respiratory Questionnaire responders (RR = 0.99; 95% CI, 0.92-1.06; P = 0.77), adverse events (RR= 1.07; 95% CI, 0.90-1.27; P = 0.42), serious adverse events (RR = 1.02; 95% CI, 0.88-1.18; P = 0.81), mortality (RR = 1.10; 95% CI, 0.65-1.86; P = 0.72), risk of pneumonia (RR = 0.86; 95% CI, 0.62-1.18; P = 0.34), and risk of cardiovascular events (RR = 1.22; 95% CI, 0.91-1.65; P = 0.18). Implications: Compared with separate triple therapy, single inhaler triple therapy appears to improve lung function in patients with moderate to severe COPD, especially in terms of forced expiratory volume in 1 second advantages. Single inhaler triple therapy may be a feasible and simplified option for patients with moderate to severe COPD; however, this conclusion needs to be further confirmed by future randomized controlled trials. (Clin Ther. 2022;XX:XXX–XXX) © 2022 Elsevier HS Journals, Inc.