Sub-analysis of trial findings showed slower lung decline with higher budesonide in combo

In patients with moderate-to-severe COPD, adding an inhaled corticosteroid to dual and triple therapy reduced yearly decline in lung function compared to no steroid treatment in a sub-group analysis of data from the phase III ETHOS study.

Compared to dual treatment with a long-acting muscarinic antagonist (LAMA) plus a long-acting β2 agonist (LABA), combination therapies that included an inhaled corticosteroid (ICS) were associated with slower decline in lung function, measured by forced expiratory volume in 1 second (FEV1) and FEV1 area under the curve from 0-4 hours (AUC0-4) over the course of a year.

The sub-analysis of phase III findings from the landmark ETHOS trial were reported in a poster presentation this week at CHEST 2020 — the virtual meeting of the American College of Chest Physicians.

The phase III ETHOS trial, published last summer in the New England Journal of Medicine, showed a signal for mortality reduction among patients with moderate-to-severe COPD who were treated with the fixed-dose triple therapy — budesonide/ glycopyrrolate/formoterol fumarate (Breztri Aerosphere) — at higher (320 µg) budesonide doses.

Two doses of budesonide — 160 μg and 320 μg — were evaluated in the trial, which compared twice-daily doses of the triple therapy with dual treatment with the LAMA glycopyrrolate and the LABA formoterol or formoterol and budesonide.

At both budesonide doses, twice-daily treatment with the single inhaler triple therapy was associated with significantly lower rates of moderate-to-severe COPD exacerbations, compared with the dual treatments, reported Klaus Rabe, MD, of the Airway Research Center North in Grosshansdorf, Germany.

Treatment with either triple-therapy regimen was also associated with significantly improved patient-reported outcomes, compared with dual therapy, the AstraZeneca-funded trial showed.

But only the 320-μg budesonide triple-therapy group showed a signal of a lower risk for death from any cause. Patients treated with the higher-dose budesonide triple therapy had a 46% lower death risk than patients in the glycopyrrolate-formoterol dual-therapy group.

The original trial included 8,509 patients with moderate-to-severe COPD randomized in similar numbers to treatment with twice-daily inhaled, fixed-dose triple therapy (160-μg or 320-μg budesonide/18-μg glycopyrrolate/9.6-μg formoterol [BGF]), or dual therapy with 18-μg glycopyrrolate/9.6-μg formoterol (GFF) or 320-μg budesonide/9.6-μg formoterol (BFF).

The newly reported sub-analysis of the trial, which examined patient pulmonary function as the primary endpoint, included data on just over 3,000 ETHOS participants.

In an effort to reduce variability and synthesize information in the analysis, the rates of decline in pre-dose trough FEV1 and FEV1 AUC0-4 over 52 weeks were assessed in the pooled ICS-containing treatment arms (BGF metered dose inhaler [MDI] 320/18/9.6 μg; BGF MDI 160/18/9.6 μg; and BFF MDI 320/9.6 μg) versus GFF MDI 18/9.6 μg (non-ICS-containing treatment arm).

The pulmonary function test modified intent-to-treat population included a total of 3,088 patients (pooled ICS group, n=2,309; GFF MDI 18/9.6 μg, n=779; mean age 64.4 years; 52.8% male; 76.5% used inhaled corticosteroids at screening; baseline post bronchodilator FEV1 % predicted, 42.5–43.1% across individual treatment groups).

The adjusted rate (SE) of decline in pre-dose trough FEV1 over 52 weeks in the pooled ICS-containing treatment group was 37.7 mL/year (5.0) versus 54.0 mL/year (8.9) in GFF MDI 18/9.6 μg (treatment difference, –16.4 mL/year [95% CI –36.4 to 3.6]).

The adjusted rate (SE) of decline in FEV1 AUC0-4 over 52 weeks in the pooled ICS-containing treatment group was 56.1 mL/year (4.7) versus 63.6 mL/year (8.5) in GFF MDI 18/9.6 μg (treatment difference, –7.5 mL/year [95% CI –26.5, to 11.6]).

ETHOS researcher Gary Ferguson, MD, and colleagues concluded that despite the severity of disease in this population, their analysis identified a trend for lower rates of lung function decline in patients receiving an inhaled corticosteroid-containing treatment relative to the treatment that did not contain an inhaled corticosteroid.

“In patients with moderate-to-very severe COPD, the use of an inhaled corticosteroid in dual and triple therapy may reduce the yearly decline in lung function versus LAMA/LABA treatment,” they wrote.

  1. Adding an inhaled corticosteroid to dual and triple therapy appeared to reduce yearly decline in lung function compared to no steroid treatment in patients with moderate-to-severe COPD.

  2. Combination therapies that included an inhaled corticosteroid (ICS) were associated with slower decline in lung function, measured by forced expiratory volume in 1 second (FEV1) and FEV1 area under the curve from 0-4 hours (AUC0-4) over the course of a year.

Salynn Boyles, Contributing Writer, BreakingMED™

Ferguson reported receiving fees from AstraZeneca, including consulting, medical advisor, and speaking fees, as well as consulting, speaking, and other fees from GlaxoSmithKline.

Several ETHOS study researchers reported being employees of AstraZeneca or having other financial relationships with the company.

Cat ID: 154

Topic ID: 89,154,192,154,195,225,925,224