title: Recombinant Human C1-Esterase Inhibitor to Treat Acute Hereditary Angioedema Attacks in Adolescents.
abstract: BACKGROUND
  Recombinant human C1-esterase inhibitor (rhC1-INH) is efficacious and well tolerated for managing hereditary angioedema (HAE) attacks in adults. However, there are insufficient data on its efficacy and safety in adolescents.
  
  
  OBJECTIVE
  To evaluate the efficacy and safety profiles of rhC1-INH for acute HAE attacks in adolescents.
  
  
  METHODS
  Adolescents (aged 12-18 y) with HAE enrolled in 2 randomized controlled trials and 2 open-label extension trials were included and received intravenous rhC1-INH for acute attacks. Times to the beginning of sustained symptom relief (visual analog scale change from baseline ≥20 mm) and minimal symptoms (visual analog scale score of <20 mm across locations) were assessed. Safety parameters included hypersensitivity reactions, anti-rhC1-INH antibodies, and host-related impurities.
  
  
  RESULTS
  Sixteen adolescents (50 attacks, aged 14-18 y) received rhC1-INH. Attacks were managed with single-dose rhC1-INH 50 U/kg (46.0%) and single-dose rhC1-INH 2100 U (16%), and 32.0% were treated with additional doses after receiving an initial rhC1-INH 2100 U dose (total dose, 4200-6300 U). Most attacks (88.0%) occurred at a single location; 59.1% (26 of 44) were abdominal. Across the first 5 attacks, median times to the beginning of symptom relief ranged from 19.0 to 78.5 minutes; median times to minimal symptoms ranged from 120 to 190 minutes. Pharmacokinetics showed that rhC1-INH restored functional plasma C1-esterase inhibitor levels to the normal (>70%) range for almost all evaluable patients. No severe or drug-related adverse events or hypersensitivity reactions occurred. No treatment-emergent antibodies to rhC1-INH or host-related impurities were observed.
  
  
  CONCLUSIONS
  rhC1-INH is efficacious and well tolerated among adolescents with HAE.
authors.affiliation: Baker Allergy Asthma Dermatology Research Center, LLC, Portland, Ore. Electronic address: jameswbaker@aadrc.com.
authors.forename: James W
authors.initials: JW
authors.lastname: Baker
authors.affiliation: Allergy and Immunology Unit, Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avner
authors.initials: A
authors.lastname: Reshef
authors.affiliation: Department of Allergology and Immunology, University of Medicine and Pharmacy, Mures County Hospital, Tirgu Mures, Romania.
authors.forename: Dumitru
authors.initials: D
authors.lastname: Moldovan
authors.affiliation: Salix Pharmaceuticals, Raleigh, NC.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Harper
authors.affiliation: Pharming Technologies BV, Leiden, the Netherlands.
authors.forename: Anurag
authors.initials: A
authors.lastname: Relan
authors.affiliation: Department of Medicine, Division of Rheumatology, Allergy, & Immunology, University of California San Diego, San Diego, Calif.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Riedl
mesh_terms: D000293:Adolescent; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D050718:Complement C1 Inhibitor Protein / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D016896:Treatment Outcome
chemical_list: D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human
keywords: Adolescent; C1-esterase; Efficacy; Hereditary angioedema; Pharmacokinetics; Ruconest; Safety