title: Outcomes after ecallantide treatment of laryngeal hereditary angioedema attacks.
abstract: BACKGROUND
  Hereditary angioedema (HAE) is a rare disorder associated with episodic attacks of well-demarcated angioedema. Attacks that affect the larynx can result in life-threatening airway obstruction.
  
  
  OBJECTIVE
  To examine efficacy and safety of ecallantide treatment for laryngeal HAE attacks.
  
  
  METHODS
  Data were combined from 4 clinical studies (EDEMA2, EDEMA3, EDEMA4, and DX-88/19) evaluating 30 mg of subcutaneous ecallantide for treatment of acute HAE attacks. Efficacy was assessed using 2 validated, HAE-specific, patient-reported outcome measures. The change in Mean Symptom Complex Severity (MSCS) score indicates change in symptom severity; a negative score indicates improvement. The calculated minimally important difference (MID) for change in severity is -0.30. The Treatment Outcome Score (TOS) measures treatment response. A positive score indicates improvement; the calculated MID is 30.
  
  
  RESULTS
  Overall, 98 patients received ecallantide for 220 laryngeal attacks. The mean ± SD change in MSCS score was -1.1 ± 0.73 and -1.6 ± 0.68 at 4 and 24 hours, respectively. The mean ± SD TOS was 73.5 ± 35.8 and 85.5 ± 27.8 at 4 and 24 hours, respectively. Median time to significant improvement was 185 minutes (95% confidence interval, 167-226). One attack required intubation. Four treatment-emergent serious adverse events were reported, including 2 HAE attacks that resulted in hospitalization and 2 anaphylactic reactions. One of these reactions required treatment with epinephrine, but both patients recovered fully. There were no deaths.
  
  
  CONCLUSIONS
  In this large attack series, ecallantide was effective for treatment of laryngeal HAE attacks. There is a risk of hypersensitivity, including anaphylaxis, consistent with product labeling. As such, ecallantide should be administered under the supervision of a health care professional.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before implementation of registration requirements); NCT00262080 for EDEMA3, NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19.
authors.affiliation: Brigham and Women's Hospital, Boston, MA 02467, USA. asheffer@partners.org
authors.forename: Albert L
authors.initials: AL
authors.lastname: Sheffer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: MacGinnitie
authors.forename: Marilyn
authors.initials: M
authors.lastname: Campion
authors.forename: Leslie E
authors.initials: LE
authors.lastname: Stolz
authors.forename: William E
authors.initials: WE
authors.lastname: Pullman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000707:Anaphylaxis / Q000188:drug therapy / Q000209:etiology; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004837:Epinephrine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007830:Larynx / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D012306:Risk; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010455:Peptides; C511194:ecallantide; D004837:Epinephrine