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Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD.
- Source :
-
The New England journal of medicine [N Engl J Med] 2020 Jul 02; Vol. 383 (1), pp. 35-48. Date of Electronic Publication: 2020 Jun 24. - Publication Year :
- 2020
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Abstract
- Background: Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β <subscript>2</subscript> -agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.<br />Methods: In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.<br />Results: The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg-budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg-budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate-formoterol group (2120 patients), and 1.24 in the budesonide-formoterol group (2131 patients). The rate was significantly lower with 320-μg-budesonide triple therapy than with glycopyrrolate-formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide-formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P = 0.003). Similarly, the rate was significantly lower with 160-μg-budesonide triple therapy than with glycopyrrolate-formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide-formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P = 0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate-formoterol group.<br />Conclusions: Triple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate-formoterol or budesonide-formoterol. (Funded by AstraZeneca, ETHOS ClinicalTrials.gov number, NCT02465567.).<br /> (Copyright © 2020 Massachusetts Medical Society.)
- Subjects :
- Administration, Inhalation
Adrenergic beta-2 Receptor Agonists adverse effects
Adult
Aged
Aged, 80 and over
Budesonide adverse effects
Double-Blind Method
Drug Combinations
Female
Forced Expiratory Volume drug effects
Formoterol Fumarate adverse effects
Glucocorticoids adverse effects
Glycopyrrolate adverse effects
Humans
Intention to Treat Analysis
Kaplan-Meier Estimate
Male
Middle Aged
Muscarinic Antagonists adverse effects
Pulmonary Disease, Chronic Obstructive mortality
Adrenergic beta-2 Receptor Agonists administration & dosage
Budesonide administration & dosage
Formoterol Fumarate administration & dosage
Glucocorticoids administration & dosage
Glycopyrrolate administration & dosage
Muscarinic Antagonists administration & dosage
Pulmonary Disease, Chronic Obstructive drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 383
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32579807
- Full Text :
- https://doi.org/10.1056/NEJMoa1916046