Comparative effectiveness and safety of different types of LABA/LAMA versus LABA/ICS fixed-dose combinations in COPD: a propensity score-inverse probability of treatment weighting cohort study

Link to article at PubMed

Chest. 2021 May 20:S0012-3692(21)00952-1. doi: 10.1016/j.chest.2021.05.025. Online ahead of print.


BACKGROUND: Despite multiple available fixed-dose combinations (FDCs) of inhaled long-acting β2-agonists (LABAs)/long-acting muscarinic antagonists (LAMAs) and LABA/inhaled corticosteroids (ICSs) in chronic obstructive pulmonary disease (COPD), uncertainty remains in their comparative effects.

RESEARCH QUESTION: Can comparative effectiveness and safety of LABA/LAMA and LABA/ICS FDCs vary by different individual components of the dual combinations in COPD?

STUDY DESIGN AND METHODS: We conducted a new user, propensity score-inverse probability of treatment weighting cohort study to compare effectiveness and safety of two frequently used LABA/LAMA FDCs (indacaterol/glycopyrronium and vilanterol/umeclidinium) versus three commonly prescribed LABA/ICS FDCs (salmeterol/fluticasone, formoterol/budesonide, and formoterol/beclomethasone), utilizing the Taiwanese nationwide healthcare claims from 2014 to 2017. The primary effectiveness outcome was the annual moderate-to-severe exacerbation rate, and safety outcomes included risks of severe pneumonia and cardiovascular disease requiring hospitalization. Weighted generalized linear mixed models and Cox proportional hazard models were employed to assess the effectiveness and safety outcomes, respectively.

RESULTS: Patients with COPD initiating indacaterol/glycopyrronium and vilanterol/umeclidinium had an 11% (incidence rate ratio [IRR] 0.89; 95% CI, 0.80-0.98) and 20% (IRR 0.80; 95% CI, 0.71-0.90) reduced annual rate of moderate-to-severe exacerbations, respectively, than those initiating salmeterol/fluticasone, but had a similar rate as those initiating formoterol/budesonide or formoterol/beclomethasone. Both LABA/LAMA FDCs compared to salmeterol/fluticasone and vilanterol/umeclidinium versus formoterol/beclomethasone, were associated with a 27% (hazard ratio [HR] 0.73; 95% CI, 0.59-0.90) to 42% (HR 0.58; 95% CI, 0.48-0.70) reduced pneumonia risk. Cardiovascular risk was comparable in five groups. An intra-class difference existed in rates of moderate-to-severe COPD exacerbation and risks of pneumonia among LABA/ICS FDCs but not between LABA/LAMA FDCs.

INTERPRETATION: Both LABA/LAMAs versus salmeterol/fluticasone are associated with a lower exacerbation rate and pneumonia risk, but exhibit similar effectiveness and safety outcomes compared with formoterol/beclomethasone or formoterol/budesonide, suggesting that comparative effects may differ by individual components of the dual therapies in COPD.

PMID:34023320 | DOI:10.1016/j.chest.2021.05.025

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