title: An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis.
abstract: OBJECTIVE
  The role of interleukin (IL)-5 in the pathogenesis of eosinophilic esophagitis (EoE) has been established in animal models; anti-IL-5 therapy has been reported to be effective in adults. We investigated whether IL-5 has a role in accumulation of esophageal eosinophils in children with EoE and whether therapy with mepolizumab, an antibody against IL-5, reduces the number of esophageal intraepithelial eosinophils in children with EoE.
  
  
  METHODS
  We performed an international, multicenter, double-blind, randomized, prospective study of 59 children with EoE, defined as baseline peak count of esophageal intraepithelial eosinophils of ≥ 20 in at least 1 high-power field (hpf). Patients received an infusion every 4 weeks (a total of 3 infusions) of 0.55, 2.5, or 10 mg/kg mepolizumab. No placebo group was used.
  
  
  RESULTS
  Baseline peak and mean esophageal intraepithelial eosinophil counts were (mean ± SE) 122.5 ± 8.78 and 39.1 ± 3.63 per hpf, respectively. Four weeks after the third infusion, peak eosinophil counts were <5 per hpf in 5 of 57 children (8.8%); we did not observe differences among groups given different doses of mepolizumab. Reduced peak and mean eosinophil counts, to <20 per hpf, were observed in 18 of 57 (31.6%) and 51 of 57 (89.5%) children, respectively. Peak and mean esophageal intraepithelial eosinophil counts decreased significantly to 40.2 ± 5.17 and 9.3 ± 1.25 per hpf, respectively (P < .0001). An analysis to evaluate predictors of response associated a higher mean baseline esophageal intraepithelial eosinophil count with a greater reduction in mean count (P < .0001).
  
  
  CONCLUSIONS
  IL-5 is involved in the pathogenesis of EoE in children. Mepolizumab, an antibody against IL-5, reduces esophageal eosinophilic inflammation in these patients.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. amal.assa'ad@cchmc.org
authors.forename: Amal H
authors.initials: AH
authors.lastname: Assa'ad
authors.forename: Sandeep K
authors.initials: SK
authors.lastname: Gupta
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Collins
authors.forename: Mike
authors.initials: M
authors.lastname: Thomson
authors.forename: Amy T
authors.initials: AT
authors.lastname: Heath
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Smith
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Perschy
authors.forename: Cynthia H
authors.initials: CH
authors.lastname: Jurgensen
authors.forename: Hector G
authors.initials: HG
authors.lastname: Ortega
authors.forename: Seema S
authors.initials: SS
authors.lastname: Aceves
mesh_terms: D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D057765:Eosinophilic Esophagitis / Q000188:drug therapy* / Q000473:pathology*; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D004947:Esophagus / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D015848:Interleukin-5 / Q000037:antagonists & inhibitors* / Q000276:immunology; D007391:International Cooperation; D008297:Male; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015848:Interleukin-5; C434107:mepolizumab