Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma

N Eng J Med. May 21, 2018

DOI: 10.1056/NEJMoa1804093

Klaus F. Rabe, M.D., Ph.D., Parameswaran Nair, M.D., Ph.D., Guy Brusselle, M.D., Ph.D., Jorge F. Maspero, M.D., Mario Castro, M.D., Lawrence Sher, M.D., Hongjie Zhu, Ph.D., Jennifer D. Hamilton, Ph.D., Brian N. Swanson, Ph.D., Asif Khan, M.B., B.S., M.P.H., Jingdong Chao, Ph.D., Heribert Staudinger, M.D., Ph.D., et al.

Abstract

BACKGROUND

Dupilumab is a fully human anti–interleukin-4 receptor α monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown.

METHODS

We randomly assigned 210 patients with oral glucocorticoid–treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV1) before bronchodilator use were also assessed.

RESULTS

The percentage change in the glucocorticoid dose was −70.1% in the dupilumab group, as compared with −41.9% in the placebo group (P<0.001); 80% versus 50% of the patients had a dose reduction of at least 50%, 69% versus 33% had a dose reduction to less than 5 mg per day, and 48% versus 25% completely discontinued oral glucocorticoid use. Despite reductions in the glucocorticoid dose, in the overall population, dupilumab treatment resulted in a severe exacerbation rate that was 59% (95% confidence interval [CI], 37 to 74) lower than that in the placebo group and resulted in an FEV1 that was 0.22 liters (95% CI, 0.09 to 0.34) higher. Injection-site reactions were more common with dupilumab than with placebo (9% vs. 4%). Transient blood eosinophilia was observed in more patients in the dupilumab group than in the placebo group (14% vs. 1%).

CONCLUSIONS

In patients with glucocorticoid-dependent severe asthma, dupilumab treatment reduced oral glucocorticoid use while decreasing the rate of severe exacerbations and increasing the FEV1. Transient eosinophilia was observed in approximately 1 in 7 dupilumab-treated patients. (Funded by Sanofi and Regeneron Pharmaceuticals; LIBERTY ASTHMA VENTURE ClinicalTrials.gov number, NCT02528214.)

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Editor: Juan C. Ivancevich, MD

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