title: Use of ecallantide in pediatric hereditary angioedema.
abstract: OBJECTIVE
  Hereditary angioedema (HAE) due to C1-inhibitor deficiency is a rare autosomal dominant disease that manifests as sudden unpredictable attacks of subcutaneous or submucosal edema affecting the skin, intestine, and upper airway. Ecallantide is a plasma kallikrein inhibitor indicated for treatment of HAE attacks in patients aged 16 years and older. This analysis examines safety and efficacy of ecallantide for treatment of HAE attacks in patients <18 years of age.
  
  
  METHODS
  Data for patients aged 9 to 17 years treated subcutaneously with 30 mg ecallantide or placebo were pooled from 4 clinical studies (2 double-blind, placebo-controlled and 2 open-label). Efficacy end points included 2 HAE-specific patient-reported outcome measures: mean symptom complex severity (MSCS) score and treatment outcome score (TOS). Times to initial improvement, sustained improvement, and complete or near-complete symptom resolution were calculated. Treatment-emergent adverse events were examined.
  
  
  RESULTS
  Overall, 29 pediatric patients were included; 25 of them received ecallantide for 62 total HAE attacks, and 10 received placebo for 10 total attacks. Ecallantide-treated attacks revealed clinically relevant reduction in symptom severity at 4 hours postdosing based on mean change in MSCS score (-1.4 ± 0.9 ecallantide versus -0.9 ± 0.6 placebo) and TOS (73.9 ± 35.50 ecallantide versus 45.0 ± 43.78 placebo). Patients treated with ecallantide showed rapid improvement in symptoms (median time to complete or near-complete symptom resolution: 181 minutes). No serious adverse events related to treatment were observed.
  
  
  CONCLUSIONS
  Ecallantide appears effective for HAE attacks in adolescents, with rapid symptom improvement. No unexpected safety issues were identified.
authors.affiliation: Division of Immunology, Boston Children’s Hospital, Boston, Massachusetts 02115, USA. andrew.macginnitie@childrens.harvard.edu
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: MacGinnitie
authors.forename: Mark
authors.initials: M
authors.lastname: Davis-Lorton
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Stolz
authors.forename: Raffi
authors.initials: R
authors.lastname: Tachdjian
mesh_terms: D000293:Adolescent; D000367:Age Factors; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D018849:Controlled Clinical Trials as Topic; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008297:Male; D008404:Massachusetts; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010455:Peptides; C511194:ecallantide; D007610:Kallikreins
keywords: C1-inhibitor; angioedema; ecallantide; hereditary angioedema; pediatric; plasma kallikrein