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N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.

Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.

Author information

1
From the Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (E.H.B.); the Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Asthma Institute at the University of Pittsburgh Medical Center-University of Pittsburgh School of Medicine, Pittsburgh (S.E.W.); the Lung Institute of Western Australia, Nedlands, and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley - both in Australia (P.J.T.); Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC (C.M.P., S.W.Y., H.G.O.); and Clinical Statistics, GlaxoSmithKline, Stockley Park (O.N.K.), and the Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford (I.D.P.) - both in the United Kingdom.

Abstract

BACKGROUND:

Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.

METHODS:

In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, we compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of reduction in the glucocorticoid dose (90 to 100% reduction, 75 to less than 90% reduction, 50 to less than 75% reduction, more than 0 to less than 50% reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control during weeks 20 to 24, or withdrawal from treatment). Other outcomes included the rate of asthma exacerbations, asthma control, and safety.

RESULTS:

The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group (95% confidence interval, 1.25 to 4.56; P=0.008). The median percentage reduction from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as compared with no reduction in the placebo group (P=0.007). Despite receiving a reduced glucocorticoid dose, patients in the mepolizumab group, as compared with those in the placebo group, had a relative reduction of 32% in the annualized rate of exacerbations (1.44 vs. 2.12, P=0.04) and a reduction of 0.52 points with respect to asthma symptoms (P=0.004), as measured on the Asthma Control Questionnaire 5 (in which the minimal clinically important difference is 0.5 points). The safety profile of mepolizumab was similar to that of placebo.

CONCLUSIONS:

In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. (Funded by GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.).

PMID:
25199060
DOI:
10.1056/NEJMoa1403291
[Indexed for MEDLINE]
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