Dupilumab Associated with Reduced Oral Corticosteroids in Severe Asthma, Regardless of Baseline OCS Dose

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Dupilumab may reduce exacerbations and improve lung function while reducing oral corticosteroid (OCS) use in patients with OCS-dependent severe asthma regardless of baseline OCS dose, according to new research.

The findings were presented at the annual meeting of the American College of Chest Physicians (CHEST 2021), held in Orlando, Florida, and virtually between October 17-20, 2021.

The study was a post hoc analysis of the phase 3 VENTURE clinical trial, which showed that compared with placebo, dupilumab 300 mg given every 2 weeks reduced OCS maintenance dose and severe asthma exacerbation rate and improved pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) independent of baseline eosinophils in patients aged ≥12 years with OCS-dependent severe asthma.

Authors of the post hoc analysis, led by Mario Castro, MD, from the University of Kansas School of Medicine, evaluated clinical outcomes in patients grouped by baseline optimized OCS, analyzing the following endpoints:

1. OCS dose
2. Proportion of patients no longer requiring OCS at week 24
3. Adjusted annualized severe exacerbation rate
4. Least squares (LS) mean change from baseline in pre- and post-BD FEV1 at week 24

Among patients who received an OCS dose of <10 mg per day at baseline, those in the dupilumab (n=46) and placebo (n=36) arms received a mean baseline OCS dose of 6.1 mg/day and 6.2 mg/day, respectively. Participants with a baseline OCS dose of ≥10 mg/day received mean OCS dosesof 14.5 mg/day in the dupilumab (n=57) group and 14.6 mg/day in the placebo (n=71) group at baseline.

OCS reduction

Investigators found that compared with placebo, treatment with dupilumab was associated with a decrease in the daily OCS dose from baseline to week 24 in participants that received OCS doseof <10 mg/day (LS mean difference, 2.1 mg; 95% confidence interval [CI], 0.8–3.3; P<.01) and in those receiving ≥10 mg/day (LS mean difference, 3.3 mg; 95% CI, 1.0–5.5; P<.01), according to the study abstract.

In participants with a baseline OCS dose <10 mg/day, 72% of dupilumab-treated patients no longer required OCS at week 24, compared with 42% of placebo-treated patients (odds ratio [OR], 3.8; 95% CI, 1.4-10; P<.01). Similarly, a higher proportion of dupilumab-treated patients with a baseline OCS dose of ≥10 mg/day stopped OCS at week 24 compared with placebo (37% vs 23%; OR, 2.3; 95% CI, 1.0-5.4; P<.05). Researchers noted that not all patients with a baseline daily OCS dose of ≥10 mg were eligible for down-titration to 0 mg/day per the study’s protocol.

Exacerbation rate down, lung function up

Dupilumab significantly reduced the annualized rate of severe asthma exacerbations by 71% among patients with a baseline daily OCS dose of <10 mg (P<.01) and 48% in those with a baseline daily OCS dose of ≥10 mg (P<.05), according to the abstract.

At week 24, treatment dupilumab compared to placebo was associated with improved pre-BD FEV1 in patients with a daily baseline OCS dose ≥10 mg compared with placebo (LS mean difference, 0.26 L; 95% CI, 0.09-0.43; P<.01). Researchers also found dupilumab-associated improvements in pre-BD FEV1 among patients with a baseline daily OCS dose of <10 mg (LS mean difference, 0.2 L; -0.04 to -0.33; P>.05).

Compared with placebo, dupilumab was associated with significant improvements in post-BD FEV1 at week 24 in patients with baseline OCS <10 mg/day (LS mean difference, 0.20 L; 95% CI, 0.05–0.35; P<.05) and ≥10 mg/day (LS mean difference, 0.18 L; 95% CI, 0.02–0.34; P<.05).

“Dupilumab significantly reduced OCS dose, improved the odds of no longer requiring OCS, and improved clinical outcomes regardless of BL OCS dose in pts [patients] with OCS-dependent severe asthma,” concluded authors.

Reference: Ribas CD, Maspero J, Castro M, et al. Dupilumab reduced oral corticosteroid use and improved clinical outcomes regardless of baseline OCS dose in patients with uncontrolled, severe asthma in the Liberty Asthma VENTURE study. CHEST. 2021:160;A1893-1897.