Triple versus dual inhaler therapy in moderate‐to‐severe COPD: A systematic review and meta‐analysis of randomized controlled trials

Abstract

Introduction Treatment of chronic obstructive pulmonary disease (COPD) is evolving specially with triple inhaler therapy. Objectives To perform a meta‐analysis to ascertain the safety and efficacy of triple inhaler therapy consisting of an inhaled‐glucocorticoid (ICS), long‐acting muscarinic antagonist (LAMA) and long‐acting beta2‐agonist (LABA) when compared with dual therapy (ICS‐LABA or LAMA‐LABA). Methods We performed an electronic database search to include randomized controlled trials (RCTs) comparing between triple and dual inhalers. Pooled rate‐ratio (RR) or odds‐ratio (OR) for dichotomous data and weighted mean difference (MD) for continuous data were calculated with their corresponding 95% confidence interval (CI). Results Our study included 12 RCTs totaling 19,322 patients, mean age of 65 ± 8.2 years and 68.2% were male. Pooled analysis demonstrated a significant reduction in moderate‐to‐severe COPD exacerbations with triple therapy (RR 0.75; 95% CI 0.69‐0.83; P < 0.01). Additionally, triple therapy caused significant increase in trough FEV1 (MD 0.09 L; 95% CI 0.07‐0.12; P < 0.01), significant reduction in the mean St. George's Respiratory Questionnaire (SGRQ) score (MD −1.67; 95% CI −2.02‐ −1.31; P < 0.01), and more patients experienced ≥ 4 points reduction of SGRQ score (OR 1.27; 95% CI 1.19‐1.35; P < 0.01). Triple therapy was associated with an increased risk of pneumonia when compared to LABA/LAMA (OR 1.25; 95% 1.03‐1.97; P = 0.03) but there were no significant differences in other adverse events between triple and dual inhalers. Conclusions Among patients with moderate‐to‐severe COPD, triple inhaler therapy was associated with a reduction of moderate‐to‐severe COPD exacerbations, improved lung function and improved quality of life when compared to dual inhaler therapy but with an increased pneumonia risk.

Triple Therapy Versus Dual Bronchodilation and Inhaled Corticosteroids/Long-Acting β-Agonists in COPD: Accumulating Evidence from Network Meta-Analyses

“…In a more recent meta-analysis that excluded pilot or cohort studies, studies that evaluated de-escalation from triple to dual therapy, casecontrol studies, retrospective studies and subgroup analyses, 12 RCTs with 19,322 patients were included in the final evaluation [23]. Also this study showed a significant reduction in moderate-to-severe AECOPDs with triple therapy (rate ratio, 0.75), an increase in trough FEV 1 (0.09 l), significant reduction in the mean SGRQ score (-1.67) with more patients experiencing C 4-point reduction of the SGRQ score and an increased risk of pneumonia compared with LABA/LAMA (odds ratio, 1.25).…”

Efficacy of Budesonide/Glycopyrronium/Formoterol Fumarate Metered Dose Inhaler (BGF MDI) Versus Other Inhaled Corticosteroid/Long-Acting Muscarinic Antagonist/Long-Acting β2-Agonist (ICS/LAMA/LABA) Triple Combinations in COPD: A Systematic Literature Review and Network Meta-analysis

“…In the absence of head-to-head data, network meta-analysis (NMA) can be used to compare multiple interventions by combining direct and indirect evidence, adjusting with the use of common comparators [11]. NMA techniques have been applied to compare the efficacy of triple therapy as a class with LAMA/LABA dual therapy or bronchodilator monotherapy [12], and two pairwise meta-analyses have provided comparisons of triple therapies with ICS/LABA [13,14] or LAMA/LABA [14].…”

“…A threelevel hierarchical Bayesian NMA model was used to determine the exacerbation rate per patient per year as well as the following outcomes at week 24: changes from baseline in predose trough forced expiratory volume in 1 s (FEV 1 ), post-dose peak FEV 1 , and St. George's Respiratory Questionnaire (SGRQ) total score; proportion of SGRQ responders; and Transition Dyspnea Index focal score. Change from baseline in rescue medication use over weeks [12][13][14][15][16][17][18][19][20][21][22][23][24] was also analyzed. Meta-regression and sensitivity analyses were used to assess heterogeneity across studies.…”

Health-Related Quality of Life Assessment Using Single-Inhaler Dual Versus Triple Therapy in Chronic Obstructive Pulmonary Disease Patients

“…First, these trials were longer in duration, have used different doses of drugs, have used different drug combinations of ICS, LABA, and LAMA were majorly conducted as randomized controlled trials, etc. [28].…”