Efficacy, Safety of Dupilumab in Corticosteroid-Dependent Severe Asthma
This article is part of MPR's coverage of the American Thoracic Society's International Conference, taking place in San Diego, California. Our staff will report on medical research related to asthma and other respiratory conditions, conducted by experts in the field. Check back regularly for more news from ATS 2018.
SAN DIEGO — Subcutaneous dupilumab 300mg significantly reduced the use of oral corticosteroids while simultaneously improving forced expiratory volume in 1 second (FEV1) and reducing severe exacerbations when given every 2 weeks to participants with corticosteroid-dependent severe asthma, according to research presented at the annual American Thoracic Society International Conference, held May 18-23, 2018, in San Diego, California.
The interleukin-4 receptor alpha antagonist, dupilumab, is a monoclonal antibody approved for treating inadequately controlled moderate-to-severe atopic dermatitis in a number of countries, including Japan and the United States. Considering the significant risks associated with long-term corticosteroid use, the LIBERTY ASTHMA VENTURE phase 3, randomized, placebo-controlled, double-blind study (ClinicalTrials.gov Identifier: NCT02528214) sought to evaluate the safety and efficacy of dupilumab for 210 participants with corticosteroid-dependent severe asthma.
Study participants were aged 12 years or older and had to be on a steroid dose (5-35mg/d of prednisone/prednisolone equivalent for 6 months) during the 4 weeks before screening. They received a subcutaneous 600mg loading dose of dupilumab on day 1 of the study (or placebo), followed by 300mg subcutaneous dupilumab (or placebo) every 2 weeks for 24 weeks. Oral corticosteroid dose was down-titrated from week 4 to week 20 (after the completion of an 8- to 10-week optimization period), and then maintained for the remaining 4 weeks of the study.
The primary efficacy outcome was the percentage reduction in oral corticosteroid dose from baseline to week 24.
At week 24, participants treated with dupilumab had reduced their corticosteroid dose by 70.1% vs 41.9% in placebo, with 80% achieving a ≥50% reduction in corticosteroid dose vs 50% of placebo (odds ratio, 3.98), and 48% no longer needing corticosteroids vs 25% of placebo. Dupilumab improved FEV1 by 0.22 L and reduced severe exacerbations by 59.3% (1.6 [placebo] vs 0.65 [dupilumab]). The most common adverse events in the dupilumab-treated group were bronchitis (6.8% vs 5.6% placebo), eosinophilia (6.8% vs 0.9% placebo), eosinophil count increase (6.8% vs 0% placebo), and sinusitis (6.8% vs 3.7% placebo). Rates of conjunctivitis were similar between both groups (1.0% vs 0.9%).
Lead author Klaus F. Rabe, MD, PhD, concluded that subcutaneous dupilumab 300mg every 2 weeks “significantly reduced [oral corticosteroid] use while reducing severe exacerbations and improving FEV1 in patients with corticosteroid-dependent severe asthma regardless of baseline blood eosinophils, and was generally well tolerated.”
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Rabe KF, Nair PK, Brusselle GG, et al. Dupilumab in patients with corticosteroid-dependent severe asthma: efficacy and safety results from the randomized, double-blind, placebo-controlled phase 3 LIBERTY ASTHMA VENTURE study. Presented at: 2018 American Thoracic Society International Conference; May 18-23, 2018; San Diego, CA. Abstract 7712.