title: Long-term safety of mepolizumab for the treatment of hypereosinophilic syndromes.
abstract: BACKGROUND
  Hypereosinophilic syndromes (HESs) are chronic disorders that require long-term therapy to suppress eosinophilia and clinical manifestations. Corticosteroids are usually effective, yet many patients become corticosteroid refractory or develop corticosteroid toxicity. Mepolizumab, a humanized monoclonal anti-IL-5 antibody, showed corticosteroid-sparing effects in a double-blind, placebo-controlled study of FIP1L1/PDGFRA-negative, corticosteroid-responsive subjects with HESs.
  
  
  OBJECTIVE
  We evaluated long-term safety and efficacy of mepolizumab (750 mg) in HES.
  
  
  METHODS
  MHE100901 is an open-label extension study. The primary end point was the frequency of adverse events (AEs). Optimal dosing frequency, corticosteroid-sparing effect of mepolizumab, and development of antimepolizumab antibodies were also explored.
  
  
  RESULTS
  Seventy-eight subjects received 1 to 66 mepolizumab infusions each (including mepolizumab infusions received in the placebo-controlled trial). Mean exposure was 251 weeks (range, 4-302 weeks). The most common dosing interval was 9 to 12 weeks. The incidence of AEs was 932 events per 100 subject-years in the first year, declining to 461 events per 100 subject-years after 48 months. Serious AEs, including 1 death, were reported by the investigator as possibly due to mepolizumab in 3 subjects. The median daily prednisone dose decreased from 20.0 to 0 mg in the first 24 weeks. The median average daily dose for all subjects over the course of the study was 1.8 mg. Sixty-two percent of subjects were prednisone free without other HES medications for ≥ 12 consecutive weeks. No neutralizing antibodies were detected. Twenty-four subjects withdrew before study completion for death (n = 4), lack of efficacy (n = 6), or other reasons.
  
  
  CONCLUSIONS
  Mepolizumab was well tolerated and effective as a long-term corticosteroid-sparing agent in PDGFRA-negative HES.
authors.affiliation: Department of Internal Medicine, Hôpital Erasme, Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Florence E
authors.initials: FE
authors.lastname: Roufosse
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Kahn
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Gleich
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schwartz
authors.forename: Anish D
authors.initials: AD
authors.lastname: Singh
authors.forename: Lanny J
authors.initials: LJ
authors.lastname: Rosenwasser
authors.forename: Judah A
authors.initials: JA
authors.lastname: Denburg
authors.forename: Johannes
authors.initials: J
authors.lastname: Ring
authors.forename: Marc E
authors.initials: ME
authors.lastname: Rothenberg
authors.forename: Javed
authors.initials: J
authors.lastname: Sheikh
authors.forename: Ann E
authors.initials: AE
authors.lastname: Haig
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Mallett
authors.forename: Deborah N
authors.initials: DN
authors.lastname: Templeton
authors.forename: Hector G
authors.initials: HG
authors.lastname: Ortega
authors.forename: Amy D
authors.initials: AD
authors.lastname: Klion
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004802:Eosinophilia / Q000188:drug therapy / Q000276:immunology; D005260:Female; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013995:Time; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D061067:Antibodies, Monoclonal, Humanized; C434107:mepolizumab