title: Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks.
abstract: BACKGROUND
  C1 esterase inhibitor (C1-INH) concentrate is well established as effective therapy for hereditary angioedema (HAE). It is thought that treatment of an acute HAE attack with C1-INH as early as possible improves efficacy, but there are limited data from prospective studies supporting this recommendation.
  
  
  OBJECTIVE
  To assess the effect of time to treatment (<6 vs ≥6 hours after start of an attack) with 20 U/kg of C1-INH concentrate on efficacy.
  
  
  METHODS
  A post hoc analysis of time to treatment after start of an attack was performed for 2 studies with C1-INH concentrate: International Multicenter Prospective Angioedema C1-INH Trial (IMPACT) 1 (randomized, placebo-controlled) and IMPACT 2 (open-label, uncontrolled extension). Because of differences in study design, the data sets were analyzed separately. IMPACT 1 data were analyzed using Cox regression with hazard ratios (HRs). For IMPACT 2 data, linear regression was applied to evaluate whether earlier treatment leads to faster recovery. Descriptive statistics for treatment response were calculated for both studies.
  
  
  RESULTS
  In IMPACT 1, treatment with C1-INH within less than 6 hours after start of an attack resulted in considerably shorter times to onset of symptom relief (HR, 3.36) and complete resolution (HR, 4.30) vs placebo. The benefit of C1-INH compared with placebo was reduced when administered after 6 or more hours (HRs, 1.18 for times to onset of symptom relief and 1.61 for complete resolution). Analysis of IMPACT 2 data indicated slower complete resolution of symptoms with later start of treatment.
  
  
  CONCLUSIONS
  Early treatment with C1-INH (<6 hours) provides a better treatment response than late treatment (≥6 hours), supporting the international recommendation to treat HAE attacks as early as possible.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifiers: NCT00168103 and NCT00292981.
authors.affiliation: Penn State University College of Medicine, Hershey, Pennsylvania, USA. tcraig@hmc.psu.edu
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Rojavin
authors.forename: Thomas
authors.initials: T
authors.lastname: Machnig
authors.forename: Heinz-Otto
authors.initials: HO
authors.lastname: Keinecke
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage*; D051056:Complement Inactivating Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D061665:Time-to-Treatment; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein; D051056:Complement Inactivating Agents