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Published at www.nejm.org March 16, 2008 (10.1056/NEJMoa070812)

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ABSTRACT

Background The hypereosinophilic syndrome is a group of diseases characterized by persistent blood eosinophilia, defined as more than 1500 cells per microliter with end-organ involvement and no recognized secondary cause. Although most patients have a response to corticosteroids, side effects are common and can lead to considerable morbidity.

Methods We conducted an international, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of an anti–interleukin-5 monoclonal antibody, mepolizumab, in patients with the hypereosinophilic syndrome. Patients were negative for the FIP1L1–PDGFRA fusion gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a stable clinical status and a blood eosinophil count of less than 1000 per microliter. Patients received either intravenous mepolizumab or placebo while the prednisone dose was tapered. The primary end point was the reduction of the prednisone dose to 10 mg or less per day for 8 or more consecutive weeks.

Results The primary end point was reached in 84% of patients in the mepolizumab group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90; 95% confidence interval [CI], 1.59 to 5.26; P<0.001) with no increase in clinical activity of the hypereosinophilic syndrome. A blood eosinophil count of less than 600 per microliter for 8 or more consecutive weeks was achieved in 95% of patients receiving mepolizumab, as compared with 45% of patients receiving placebo (hazard ratio, 3.53; 95% CI, 1.94 to 6.45; P<0.001). Serious adverse events occurred in seven patients receiving mepolizumab (14 events, including one death; mean [±SD] duration of exposure, 6.7±1.9 months) and in five patients receiving placebo (7 events; mean duration of exposure, 4.3±2.6 months).

Conclusions Our study shows that treatment with mepolizumab, an agent designed to target eosinophils, can result in corticosteroid-sparing for patients negative for FIP1L1–PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov number, NCT00086658 [ClinicalTrials.gov] .)

Source Information

From the Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati (M.E.R.); the National Institute of Allergy and Infectious Diseases, Bethesda, MD (A.D.K.); Service de Médecine Interne, Hôpital Erasme, Université Libre de Bruxelles, and the Institute for Medical Immunology, Gosselies, Belgium (F.E.R.); Service de Médecine Interne, Hôpital Foch, Suresnes, France (J.E.K.); Beth Israel Deaconess Medical Center, Harvard Medical School, Boston (P.F.W.); the University of Bern, Bern, Switzerland (H.-U.S.); Virginia Commonwealth University, Richmond (L.B.S.); Children's Mercy Hospital, Kansas City, MO (L.J.R.); Technische Universität München, Munich, Germany (J.R.); Envision Pharma, Horsham, United Kingdom (E.F.G.); GlaxoSmithKline, King of Prussia, PA (A.E.H.); GlaxoSmithKline, Middlesex, United Kingdom (P.I.H.F., J.M.P.); and University of Utah School of Medicine, Salt Lake City (G.J.G.).

This article (10.1056/NEJMoa070812) was published at www.nejm.org on March 16, 2008. It will appear in the March 20 issue of the Journal.

Address reprint requests to Dr. Rothenberg at the Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave., Cincinnati, OH 45229, or at rothenberg{at}cchmc.org.

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