Clinical effectiveness and safety of dupilumab in patients with chronic obstructive pulmonary disease: A 7-year population-based cohort study - 15/11/24

Doi : 10.1016/j.jaci.2024.09.019

Chuan-Yen Sun, MD ^a,^b,^c, Yohannes Tesfaigzi, PhD ^d, Gin-Yi Lee, MD ^e, Yi-Hsuan Chen, ScM ^f, Scott T. Weiss, MD, MS ^g,^h,^{^{∗
These authors contributed equally to this work as senior authors.}}, Kevin Sheng-Kai Ma, DDS, FRSPH, FRSM ^a,^⁎^{^{∗
These authors contributed equally to this work as senior authors.}}
^a Center for Global Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa
^b Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, China
^c School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, China
^d Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
^e Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
^f Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, Md
^g Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass
^h Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Mass

^∗Corresponding author: Kevin Sheng-Kai Ma, DDS, FRSPH, FRSM, Center for Global Health, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104.Center for Global HealthPerelman School of MedicineUniversity of Pennsylvania3400 Civic Center BlvdPhiladelphiaPA19104

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Friday 15 November 2024

Abstract

Background

Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up.

Objective

This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD.

Methods

The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β₂-agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article's Online Repository at www.jacionline.org.

Results

A total of 1521 dupilumab initiators and 1521 propensity score–matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI =0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β₂-agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93).

Conclusions

In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities.

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Key words : COPD, anti–IL-4 receptor, anti–IL-13 receptor, acute exacerbations

Abbreviations used : AE, COPD, HR, MUC5AC, TSLP