Treatment of patients with the hypereosinophilic syndrome with mepolizumab.
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].).
Rothenberg
Marc E
ME
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229, USA. rothenberg@cchmc.org
Klion
Amy D
AD
Roufosse
Florence E
FE
Kahn
Jean Emmanuel
JE
Weller
Peter F
PF
Simon
Hans-Uwe
HU
Schwartz
Lawrence B
LB
Rosenwasser
Lanny J
LJ
Ring
Johannes
J
Griffin
Elaine F
EF
Haig
Ann E
AE
Frewer
Paul I H
PI
Parkin
Jacqueline M
JM
Gleich
Gerald J
GJ
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000235:genetics; D015848:Interleukin-5 / Q000276:immunology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D017211:Treatment Failure; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005938:Glucocorticoids; D015848:Interleukin-5; D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C434107:mepolizumab; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D011241:Prednisone