Treatment of patients with the hypereosinophilic syndrome with mepolizumab

Rothenberg, Marc E; Klion, Amy D; Roufosse, Florence E; Kahn, Jean Emmanuel; Weller, Peter F; Simon, Hans-Uwe; Schwartz, Lawrence B; Rosenwasser, Lanny J; Ring, Johannes; Griffin, Elaine F; Haig, Ann E; Frewer, Paul I H; Parkin, Jacqueline M; Gleich, Gerald J (2008). Treatment of patients with the hypereosinophilic syndrome with mepolizumab. New England journal of medicine NEJM, 358(12), pp. 1215-28. Waltham, Mass.: Massachusetts Medical Society MMS 10.1056/NEJMoa070812

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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].).

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
UniBE Contributor:	Simon, Hans-Uwe
ISSN:	0028-4793
ISBN:	18344568
Publisher:	Massachusetts Medical Society MMS
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:03
Last Modified:	05 Dec 2022 14:19
Publisher DOI:	10.1056/NEJMoa070812
PubMed ID:	18344568
Web of Science ID:	000254094400003
URI:	https://boris.unibe.ch/id/eprint/27540 (FactScience: 108768)