title: The effect of weight on the efficacy and safety of C1 esterase inhibitor concentrate for the treatment of acute hereditary angioedema.
abstract: BACKGROUND
  Despite the worldwide obesity epidemic, there have been very few studies investigating the influence of body weight on treatment dosing and outcomes in patients with hereditary angioedema (HAE).
  
  
  OBJECTIVE
  The purpose of this analysis was to determine whether the standard weight-based dosing recommendation of C1 esterase inhibitor (C1-INH) concentrate (20 IU/kg) is adequate in HAE patients with a high body mass index (BMI).
  
  
  METHODS
  Data from patients treated for HAE attacks with 20 IU/kg of C1-INH concentrate were retrospectively analyzed from the open-label IMPACT2 study (International Multicenter Prospective Angioedema C1-INH Trial). Patients were categorized according to BMI as being normal body weight, overweight, or obese. Efficacy end points were time to onset of symptom relief and time to complete resolution of symptoms. The safety profile was evaluated according to adverse events occurring within 7 to 9 days of treatment.
  
  
  RESULTS
  Of 57 patients, 24 (42%) were of normal body weight, 20 (35%) were overweight, and 13 (23%) were obese. Median (95% CI) time to onset of symptom relief was 0.37 hour (0.29-0.57) in normal-weight patients, 0.48 hour (0.39-0.53) in overweight patients, and 0.58 hour (0.41-0.94) in obese patients. Median time (95% CI) to complete resolution of symptoms was 15.2 hours (9.3-23.2) in normal-weight patients, 22.6 hours (11.3-44.6) in overweight patients, and 11.0 hours (5.6-23.6) in obese patients (differences not significant). There were no relevant differences in the incidence of adverse events in normal-weight patients (54%), overweight patients (30%), and obese patients (54%).
  
  
  CONCLUSIONS
  Treatment of HAE attacks with weight-based doses of C1-INH concentrate provided reliable treatment response, regardless of body weight, in these patients with HAE.
authors.affiliation: University of Cincinnati Medical Center, Cincinnati, Ohio. Electronic address: bernstja@ucmail.uc.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: CSL Behring GmbH, Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Machnig
authors.affiliation: Accovion GmbH, Marburg, Germany.
authors.forename: Heinz-Otto
authors.initials: HO
authors.lastname: Keinecke
authors.affiliation: CSL Behring GmbH, Marburg, Germany.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Whelan
authors.affiliation: Penn State University College of Medicine, Hershey, Pennsylvania.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Craig
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000188:drug therapy*; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000008:administration & dosage* / Q000009:adverse effects; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity; D050177:Overweight; D012107:Research Design; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D050718:Complement C1 Inhibitor Protein
keywords: C1 esterase inhibitor; body mass index; dosing; hereditary angioedema; obesity; pharmacokinetics