Different inhaled corticosteroid doses in triple therapy for chronic obstructive pulmonary disease: systematic review and Bayesian network meta-analysis

Abstract

A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52–0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51–0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37–0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36–0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.

Comparative effectiveness and safety of triple therapy and non-triple therapy interventions for COPD: an overview of systematic reviews

“…However, research shows that medium-dose ICS-containing plays an important role in reducing the risk of mortality, whereas high-dose ICS-containing has more advantages in reducing the risk of total exacerbation. 51 , 52 …”

Differences in the effectiveness of single, dual, and triple inhaled corticosteroid therapy for reducing future risk of severe asthma exacerbation: A systematic review and network meta-analysis

“…A network meta-analysis (NMA) is a statistical method that can be used to compare various therapies by combining direct and indirect evidence across a network of studies [ 18 , 19 ]. The benefits of different inhaled ICS therapies in reducing severe asthma exacerbations have been described in recent years through numerous systematic evaluations that incorporated NMA methodologies [ [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] ]. However, trials evaluating various therapies have adopted different strategies to account for clinical heterogeneity.…”