title: Analysis of hereditary angioedema attacks requiring a second dose of ecallantide.
abstract: BACKGROUND
  Effective treatment of acute attacks is critical in managing hereditary angioedema (HAE). Ecallantide, a plasma kallikrein inhibitor, is approved for the treatment of HAE attacks. Occasionally, a second dose is needed when treating attacks of HAE.
  
  
  OBJECTIVE
  To evaluate the characteristics of HAE attacks requiring a second dose (dose B) of ecallantide.
  
  
  METHODS
  Data from all ecallantide clinical trials (EDEMA2, EDEMA4, and DX-88/19) that allowed an open-label dose B were included in this analysis. Patient and attack characteristics potentially predictive of dose B after ecallantide were analyzed by logistic regression. A multivariate model was built using a backward selection process, incorporating variables from the univariate model with P < .20 and removing factors with the highest P value until only significant (P < .05) factors remained.
  
  
  RESULTS
  The analysis included 732 ecallantide-treated HAE attacks in 179 patients. Dose B was required in 88 attacks (12.0%), most (80.5%) for incomplete response. By attack location, 31 of 325 abdominal attacks (9.5%), 17 of 158 laryngeal attacks (10.8%), and 40 of 242 peripheral attacks (16.5%) required dose B. On the basis of the univariate analysis, baseline severity (odds ratio = 1.33, P = .15) and peripheral attack (odds ratio = 1.80, P = .01) were identified as potential predictive factors; abdominal attacks had an inverse correlation (odds ratio = 0.64, P = .055). However, the multivariate analysis identified only peripheral attacks as statistically significantly correlated (P < .05) with dose B requirement.
  
  
  CONCLUSIONS
  A single, 30-mg dose of ecallantide was effective for most HAE attacks (88.0%). Patients with peripheral attacks of HAE were more likely to require a second dose of ecallantide after 4 hours.
  
  
  BACKGROUND
  clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before registration requirements were implemented), NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19.
authors.affiliation: Institute for Asthma and Allergy, Wheaton, MD 20902, USA. hl@allergyasthma.us
authors.forename: H Henry
authors.initials: HH
authors.lastname: Li
authors.forename: Marilyn
authors.initials: M
authors.lastname: Campion
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Soteres
authors.forename: Marc
authors.initials: M
authors.lastname: Riedl
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: MacGinnitie
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Shea
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D011237:Predictive Value of Tests; D011379:Prognosis; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010455:Peptides; C511194:ecallantide