title: Assessment of rebound and relapse following ecallantide treatment for acute attacks of hereditary angioedema.
abstract: BACKGROUND
  Hereditary angioedema (HAE) is a rare genetic disease characterized by unpredictable and recurring attacks of angioedema. This study assessed potential attack rebound and relapse following treatment with ecallantide, a plasma kallikrein inhibitor approved for HAE attack treatment.
  
  
  METHODS
  Results were integrated from 2 double-blind, placebo-controlled studies of ecallantide treatment for HAE: EDEMA3-DB and EDEMA4. Symptoms were assessed by treatment outcome score (TOS), mean symptom complex severity (MSCS) score, and global response. Patients with improvement at 4 h post-dosing in all three measures followed by any sign of worsening at 24 h were considered to show potential rebound if worsening was beyond baseline or potential relapse if not beyond baseline. Likeliness of rebound or relapse was determined by the number of measures showing worsening and the magnitude of worsening. Patients receiving placebo who met the criteria for rebound/relapse were evaluated for descriptive comparison only.
  
  
  RESULTS
  Significantly more ecallantide-treated patients (42 of 70) compared to placebo (26 of 71) showed improvement in three measures at 4 h and were thus eligible for rebound/relapse (P = 0.006). Of the nine ecallantide-treated patients with signs of worsening at 24 h, none were likely rebound, one was assessed as possible rebound, one as likely relapse, and two as possible relapse. No patient with potential rebound/relapse experienced new symptoms after dosing. Medical intervention was required in one ecallantide-treated patient.
  
  
  CONCLUSIONS
  Ecallantide was efficacious for treating acute HAE attacks. Relapse was observed in a small proportion of patients, and there was little evidence of rebound.
authors: Division of Immunology/Allergy Section, University of Cincinnati, OH, USA. jonathan.bernstein@uc.edu
authors: J A
authors: JA
authors: Bernstein
authors: E P
authors: EP
authors: Shea
authors: J
authors: J
authors: Koester
authors: R
authors: R
authors: Iarrobino
authors: W E
authors: WE
authors: Pullman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000503:physiopathology* / Q000517:prevention & control; D002648:Child; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D007610:Kallikreins / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D055502:Secondary Prevention; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D010455:Peptides; C511194:ecallantide; D007610:Kallikreins