title: Characterization of anaphylaxis after ecallantide treatment of hereditary angioedema attacks.
abstract: BACKGROUND
  Ecallantide is a human plasma kallikrein inhibitor indicated for treatment of acute attacks of hereditary angioedema for patients 12 years of age and older. Ecallantide is produced in Pichia pastoris yeast cells by recombinant DNA technology. Use of ecallantide has been associated with a risk of hypersensitivity reactions, including anaphylaxis.
  
  
  OBJECTIVE
  The objective of this detailed retrospective data review was to characterize anaphylaxis cases within the ecallantide clinical trials database.
  
  
  METHODS
  Potential cases of hypersensitivity reactions in the ecallantide clinical development program were identified by examining reported adverse events. The National Institute of Allergy and Infectious Disease criteria were used to identify those events that were consistent with anaphylaxis; these cases were then reviewed in detail. Results from investigational antibody testing also were examined.
  
  
  RESULTS
  Among patients who received subcutaneous ecallantide (n = 230 patients; 1045 doses of 30 mg ecallantide), 8 patients (3.5%) had reactions that met the National Institute of Allergy and Infectious Disease criteria for anaphylaxis; none occurred on first exposure to the drug. All 8 reactions had symptom onset within 1 hour of exposure and cutaneous manifestations commonly observed in type I hypersensitivity reactions. All the reactions responded to standard management of type I hypersensitivity reactions and resolved without fatal outcomes. IgE antibody testing to ecallantide or P pastoris was not consistently positive in patients who experienced apparent type I hypersensitivity reactions.
  
  
  CONCLUSIONS
  Anaphylaxis episodes after subcutaneous ecallantide exposure have clinical features suggestive of type I hypersensitivity reactions. However, anti-ecallantide or anti-P pastoris IgE antibody status was not found to be reliably associated with anaphylaxis.
authors.affiliation: Pennsylvania State University, Department of Medicine and Pediatrics, Hershey, Pa. Electronic address: tcraig@psu.edu.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.affiliation: Institute for Asthma and Allergy, Chevy Chase, Md.
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.affiliation: US Hereditary Angioedema Association, Angioedema Center, Allergy and Immunology, University of California, San Diego, San Diego, Calif.
authors.forename: Marc
authors.initials: M
authors.lastname: Riedl
authors.affiliation: Division of Immunology/Allergy, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: Allergy and Asthma Specialists, Dallas, Tex.
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.affiliation: Division of Immunology, Boston Children's Hospital, Boston, Mass.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: MacGinnitie
authors.affiliation: Dyax Corp., Burlington, Mass.
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Stolz
authors.affiliation: Dyax Corp., Burlington, Mass.
authors.forename: Joseph
authors.initials: J
authors.lastname: Biedenkapp
authors.affiliation: Dyax Corp., Burlington, Mass.
authors.forename: Yung
authors.initials: Y
authors.lastname: Chyung
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000276:immunology; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D002648:Child; D004342:Drug Hypersensitivity / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000276:immunology; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012882:Skin Tests; D055815:Young Adult
chemical_list: D007136:Immunoglobulins; D010455:Peptides; C511194:ecallantide; D007610:Kallikreins
keywords: Allergy; Anaphylaxis; Ecallantide; HAE; Hereditary angioedema; Hypersensitivity