Patients with moderate COPD also benefit from triple therapy

The benefits of a triple fixed-dose inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting beta₂ agonist combination extend to patients with moderate as well as severe chronic obstructive pulmonary disease (COPD).

That’s according to investigators in the ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial (NCT02465567).

In a subanalysis of data on patients with moderate COPD who were enrolled in the comparison trial, the single-inhaler combination of the inhaled corticosteroid (ICS) budesonide, the long-acting muscarinic antagonist (LAMA) glycopyrrolate, and the long-acting beta₂ agonist (LABA) formoterol fumarate (BGF) showed benefits in terms of COPD exacerbations, lung function, symptoms, and quality-of-life compared with either of two dual therapy combinations (glycopyrrolate or budesonide with formoterol [GFF/BFF]).

“A moderate benefit:risk ratio was demonstrated in patients with moderate COPD, consistent with the results of the overall ETHOS population, indicating the results of the ETHOS study were not driven by patients with severe or very severe COPD,” wrote Gary T. Ferguson, MD, from the Pulmonary Research Institute of Southeast Michigan in Farmington Hills, and colleagues. Their poster was presented during the American Thoracic Society’s virtual international conference. (Abstract A2244).

As reported at ATS 2020, in the overall ETHOS population of 8,509 patients with moderate to very severe COPD the annual rate of moderate or severe COPD exacerbations was 1.08 and 1.07 for the triple combinations with 320-mcg and 160-mcg doses of budesonide, respectively, compared with 1.42 for glycopyrrolate-formoterol, and 1.24 for budesonide-formoterol.

Both triple combinations were significantly superior to the dual therapies for controlling exacerbations, Klaus F. Rabe, MD, PhD, of LungenClinic Grosshansdorf and Christian-Albrechts University Kiel (Germany), and colleagues found.

Subanalysis details

At the 2021 iteration of ATS, ETHOS investigator Dr. Ferguson and colleagues reported results for 613 patients with moderate COPD assigned to BGF 320 mcg, 604 assigned to BGF 160 mcg, 596 assigned to GFF, and 614 randomized to BFF.

Baseline demographic and clinical characteristics were similar among the groups, including age, sex, smoking status, mean COPD Assessment Test (CAT) score, mean blood eosinophil count, ICS use at screening, exacerbations in the previous year, mean postbronchodilator forced expiratory volume in 1 second (FEV₁) percentage of predicted, and mean postbronchodilator percentage reversibility.

A modified intention-to-treat (ITT) analysis showed that the rate of moderate or severe exacerbations over 52 weeks with BGF 320 mcg was 21% lower than with GFF (P = .0123), but only 4% lower than with BFF, a difference that was not statistically significant.

The BGF 160-mg dose was associated with a 30% reduction in exacerbations vs. GFF (P = .0002), and with a nonsignificant reduction of 15% compared with BFF.

­There was a numerical but not statistically significant improvement from baseline at week 24 in morning pre-dose trough FEV₁ between the BGF 320-mcg dose and GFF (difference 47 mL), and a significant improvement (90 mL) with BGF compared with BFF (P = .0006). The BGF 160-mcg dose was associated with a larger improvement (89 mL) compared with BFF (P = .0004) but not with GFF.

The FEV₁ area under the curve (AUC) of receiver operating characteristics from 0 to 4 hours was superior with BGF at both doses compared with both GFF and BFF.

Patients who used BGF 320 mcg also used significantly less rescue medication over 24 weeks compared with patients who used GFF (P < .0001) or BFF (P = .0001). There were no significant differences in rescue medication use between the BGF 160-mg dose and either of the dual therapy combinations.

Time to clinically important deterioration – defined as a greater than ­100 mL decrease in trough FEV₁, or a ­4 units increase in St. George’s Respiratory Questionnaire total score, or a treatment-emergent moderate/severe COPD exacerbation occurring up to week 52 – was significantly longer with the 320-mcg but not 160-mcg BGF dose compared with GFF (P = .0295) or BFF (P = .0172).