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N Engl J Med. 2018 Jun 28;378(26):2475-2485. doi: 10.1056/NEJMoa1804093. Epub 2018 May 21.

Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma.

Author information

1
From LungenClinic Grosshansdorf, Grosshansdorf, and Christian Albrechts University Kiel, Kiel - both in Germany (K.F.R.); McMaster University and St. Joseph's Healthcare, Hamilton, ON, Canada (P.N.); Ghent University Hospital, Ghent, Belgium (G.B.); Fundación CIDEA (Centro de Investigación de Enfermedades Alérgicas y Respiratorias), Buenos Aires (J.F.M.); Washington University School of Medicine, St. Louis (M.C.); Peninsula Research Associates, Rolling Hills Estates, CA (L.S.); Sanofi, Bridgewater, NJ (H.Z., B.N.S., H.S., G.P., C.A., A.T.); Regeneron Pharmaceuticals, Tarrytown, NY (J.D.H., J.C., N.A., M.R., B.A., N.M.H.G., N.S., G.D.Y.); and Sanofi, Chilly Mazarin, France (A.K.).

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 .).

Comment in

PMID:
29782224
DOI:
10.1056/NEJMoa1804093
[Indexed for MEDLINE]
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