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LABA/LAMA versus LABA/ICS fixed-dose combinations in the prevention of COPD exacerbations: a modeling analysis of literature aggregate data

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Abstract

Objectives

This study aimed to quantitatively compare the efficacy and safety of long-acting β2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) and LABA/inhaled corticosteroid (ICS) fixed-dose combinations (FDCs) in preventing moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations.

Methods

A literature search was performed using public databases. The time course characteristics of the probability of a moderate or severe exacerbation in stable COPD patients treated with LABA/LAMA and LABA/ICS FDCs were described by the parametric survival function. A random-effects model in a single-arm meta-analysis was used to analyze the incidence of serious adverse events (SAEs) and pneumonia.

Results

Twenty studies including 23,955 participants were included. The proportion of participants with a history of COPD exacerbation (%) in the previous year and the postbronchodilator forced expiratory volume in the first second (FEV1) (%predicted) were important factors affecting drug efficacy. After adjusting the above factors to median levels of 100% and 45.5%, respectively, the moderate or severe exacerbation rates at 52 weeks for olodaterol/tiotropium, formoterol/budesonide, indacaterol/glycopyrronium, formoterol/glycopyrronium, vilanterol/fluticasone, salmeterol/fluticasone, and vilanterol/umeclidinium were 38.3%, 41.0%, 42.6%, 47.0%, 47.5%, 47.9%, and 53.0%, respectively. In terms of safety, significant differences were observed among drugs containing different LABA/LAMA FDCs.

Conclusions

This study showed that not all LABA/LAMA FDCs were superior to LABA/ICS FDCs in safety and in preventing moderate or severe exacerbations in patients with stable COPD, providing important quantitative information for COPD-related guidelines.

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Data availability

Data specifications and applications are available from the corresponding author.

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Acknowledgements

The authors thank all staffs of the Center for Drug Clinical Evaluation, Shanghai University of Traditional Chinese Medicine.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (82174229), and Shanghai three-year Action Plan for Inheritance, Innovation and Development of traditional Chinese Medicine [ZY(2021–2023)-0401].

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Authors and Affiliations

  1. Center for Drug Clinical Evaluation Shanghai, University of Traditional Chinese Medicine, No. 1200 Cailun Road, Shanghai, China

    Yiwen Gong, Zichao Sui, Yinghua Lv, Qingshan Zheng & Lujin Li

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  1. Yiwen Gong
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  2. Zichao Sui
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Contributions

Yiwen Gong and Zichao Sui: conceptualization, data curation, formal analysis, investigation, writing—original draft, and writing—review and editing. Yiwen Gong and Zichao Sui contributed equally to this work. Yinghua Lv: data curation. Qingshan Zheng: conceptualization and funding acquisition. Lujin Li: conceptualization and methodology. Lujin Li is the corresponding author of this article, and Qingshan Zheng is the co-corresponding author.

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Correspondence to Lujin Li.

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Gong, Y., Sui, Z., Lv, Y. et al. LABA/LAMA versus LABA/ICS fixed-dose combinations in the prevention of COPD exacerbations: a modeling analysis of literature aggregate data. Eur J Clin Pharmacol 79, 1321–1332 (2023). https://doi.org/10.1007/s00228-023-03543-y

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