Efficacy of ICS versus Non-ICS Combination Therapy in COPD: A Meta-Analysis of Randomised Controlled Trials

Abstract

Background: Several large randomized clinical trials (RCTs) have assessed the efficacy and safety of inhaled corticosteroid (ICS) combination regimens versus non-ICS therapy in patients with chronic obstructive pulmonary disease (COPD) at increased risk of exacerbation risk with mixed results.

Methods: We performed a systematic literature review and meta-analysis of RCTs comparing the effect of ICS-containing combination therapy and non-ICS regimen in patients with COPD.

Results: A total of 54 RCTs (N = 57,333) reported treatment effects on various outcomes and were eligible for inclusion. Overall, the number of patients experiencing moderate/severe exacerbations was significantly lower for ICS-containing combination therapy versus non-ICS therapy (RR: 0.86 [95% CI: 0.80-0.93]). The annual rate of exacerbations was also significantly reduced by 22% (0.78 [0.72-0.86]) with ICS-containing versus non-ICS therapy. The annual rate of exacerbations requiring hospitalisation was reduced by 31% versus non-ICS therapy (0.69 [0.54-0.88]); similar reduction was observed for exacerbations requiring oral steroids (0.69 [0.66-0.73]). Overall, the effect on trough FEV1 was comparable between ICS-containing and non-ICS therapies (follow-up: 6-52 weeks); however, a significant improvement in lung function (trough FEV1) was observed for ICS/LABA versus LABA (MD: +0.04 L [0.03-0.05]) and ICS/LABA/LAMA versus LAMA (MD: +0.09 L [0.05-0.13]) regimens. In addition, a significant improvement in QoL was observed with ICS-containing versus non-ICS therapy (MD in SGRQ score: -0.90 [-1.50, -0.31]).

Conclusion: This meta-analysis demonstrated that a wide range of patients with COPD could benefit from dual and triple ICS-containing therapy.

Keywords: chronic obstructive pulmonary disease; dual therapy; exacerbation; inhaled corticosteroid; meta-analysis; triple therapy.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocols (PRISMA-P) flow diagram for the identification of studies included in the meta-analysis concerning the impact of benefit from dual and triple ICS-containing therapy versus non-ICS therapy in chronic obstructive pulmonary disease (COPD). Three publications found by hand search were included in the meta-analysis.

Figure 2

Effects of treatment on the change in trough FEV₁ (pre-dose) by therapeutic regimen.

Figure 3

Effects of treatment on the number of patients experiencing COPD exacerbations by therapeutic regimen.

Figure 4

Effects of treatment on the annual rate of COPD exacerbations by therapeutic regimen.