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Comparative Study
. 2024 Jan-Dec:18:17534666241292242.
doi: 10.1177/17534666241292242.

Comparative effectiveness and safety of escalating to triple therapy versus switching to dual bronchodilators after discontinuing LABA/ICS in patients with COPD: a retrospective cohort study

Li-Wei Wu  1 , Tzu-Chieh Lin  2 , Tzu-Han Lin  2 , Ying-Jay Liou  3   4 , Chen-Liang Tsai  5 , Kuang-Yao Yang  6   7 , Meng-Ting Wang  8
Affiliations
Comparative Study

Comparative effectiveness and safety of escalating to triple therapy versus switching to dual bronchodilators after discontinuing LABA/ICS in patients with COPD: a retrospective cohort study

Li-Wei Wu et al. Ther Adv Respir Dis. 2024 Jan-Dec.

Abstract

Background: The latest guidelines discourage the use of long-acting beta2-agonists/inhaled corticosteroids (LABA/ICS) for chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the optimal subsequent treatment after discontinuing LABA/ICS.

Objectives: To compare the effectiveness and safety of switching from LABA/ICS to triple therapy (LABA/long-acting muscarinic antagonists (LAMA)/ICS) or to dual bronchodilators (LABA/LAMA) in COPD patients.

Design: This was a new-user, active-comparator, and propensity score-matched cohort study analyzing the Taiwanese nationwide healthcare insurance claims.

Methods: We recruited COPD patients switching from LABA/ICS to triple therapy or to dual bronchodilators from 2015 to 2019. The primary effectiveness outcome was the annual rate of exacerbations, and safety outcomes included severe pneumonia and all-cause mortality. Stratification by prior exacerbations was conducted.

Results: After matching, each group comprised 1892 patients, 55% of whom experienced no exacerbations in the prior year. Treatment with LABA/LAMA/ICS versus LABA/LAMA showed comparable annual rate of moderate-to-severe exacerbations (incidence rate ratio, 1.04; 95% confidence interval (CI), 0.91-1.19). However, switching to LABA/LAMA/ICS was associated with increased risks of severe pneumonia (hazard ratio (HR), 1.65; 95% CI, 1.30-2.09) and all-cause death (HR, 1.39; 95% CI, 1.09-1.78). In patients with⩾2 prior exacerbations, LABA/LAMA/ICS versus LABA/LAMA was related to a 21% reduced rate of exacerbations but with a twofold increased pneumonia risk and a 49% elevated risk of all-cause mortality.

Conclusion: Switching from LABA/ICS to triple therapy versus dual bronchodilators in COPD patients was associated with similar rates of annual exacerbations but was related to elevated risks of severe pneumonia and all-cause mortality. Among frequent exacerbators, triple therapy was associated with lower rates of exacerbation but was accompanied by increased risks of pneumonia and mortality compared to LABA/LAMA. Careful consideration of the examined safety events is necessary when switching from LABA/ICS to triple therapy in COPD management.

Keywords: COPD; comparative effectiveness and safety; dual therapy; observational study; triple therapy.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flowchart showing the selection of the base and study cohorts. COPD, chronic obstructive pulmonary disease; GOLD, Global Initiative for Chronic Obstructive Lung Disease; ICS, inhaled corticosteroids; LABA, inhaled long-acting β2 agonists; LAMA, inhaled long-acting muscarinic antagonists.
Figure 2.
Figure 2.
Forest plots showing the (a) sensitivity analyses and (b) subgroup analyses of the annual rate of exacerbation. aHRs with 95% CIs were estimated to study the outcomes of competing risk models, GERD, and high-dimensional PS matching. bp < 0.05. CI, confidence interval; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; GERD, gastroesophageal reflux disease; HR, hazard ratio; IRR, incidence rate ratio; PS, propensity score.
Figure 3.
Figure 3.
Bar charts illustrating (a) the annual rate of COPD moderate-to-severe exacerbations and (b) incidence rate of first hospitalization for pneumonia stratified by prior exacerbation(s). ap < .05. bp < .001. CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; ICS, inhaled corticosteroids; IRR, incidence rate ratio; LABA, inhaled long-acting β2 agonists; LAMA, inhaled long-acting muscarinic antagonists.
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