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Triple Therapy Combination Reduces COPD Exacerbations, Death Risk - Pulmonology Advisor

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Patients with moderate to very severe chronic obstructive pulmonary disease (COPD) who received triple fixed doses of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2 agonist (LABA) had fewer exacerbations compared with those taking 2 of the 3 medications, according to study results published in the New England Journal of Medicine.

In the ETHOS clinical trial, researchers compared the  annual rate of moderate or severe COPD exacerbations between groups of patients with moderate to very severe COPD following treatment for 1 year (ClinicalTrial.gov Identifier: NCT02465567) Patients were randomly assigned in a 1:1:1:1 ratio to receive either a high (group 1) or low (group 2) dose of triple therapy containing the glucocorticoid budesonide, the LAMA glycopyrrolate, and the LABA formoterol, or 1 of 2 dual therapies containing glycopyrrolate and formoterol (group 3) or budesonide and formoterol (group 4).

Of the 8588 patients with moderate to very severe COPD who were included, a total of 7187 completed the trial. The annual rates of moderate to severe exacerbations were 1.08 in the high-dose triple therapy group, 1.07 in the low-dose triple therapy group, 1.42 in the glycopyrrolate-formoterol group and 1.24 in the budesonide-formoterol group. The percentage of patients who reported ≥1 adverse event was similar across treatment groups (range, 61.7%-64.5%). The most frequently reported adverse events were nasopharyngitis, COPD, and upper respiratory tract infection.

“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,” the study authors concluded. “Furthermore, despite a mortality of 1.8% overall, when the triple-therapy regimens were compared with glycopyrrolate-formoterol, a lower risk of death from any cause was observed only in the 320-µg-budesonide triple-therapy group.”


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Disclosure: This clinical trial was supported by AstraZeneca. Please see the original reference for a full list of authors’ disclosures.

Reference

Rabe KF, Martinez FJ, Ferguson GT, et al; for the ETHOS Investigators. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD [published online June 24 2020]. N Engl J Med. doi:10.1056/NEJMoa1916046

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