title: Escalating doses of C1 esterase inhibitor (CINRYZE) for prophylaxis in patients with hereditary angioedema.
abstract: BACKGROUND
  Nanofiltered C1 inhibitor (human) is approved in the United States for routine prophylaxis of angioedema attacks in patients with hereditary angioedema, a rare disease caused by a deficiency of functional C1 inhibitor.
  
  
  OBJECTIVE
  To assess the safety of escalating doses of nanofiltered C1 inhibitor (human) in patients who were not adequately controlled on the indicated dose (1000 U every 3 or 4 days).
  
  
  METHODS
  Eligible patients had >1 attack/month over the 3 months before the trial. Doses were escalated to 1500 U every 3 or 4 days for 12 weeks, at which point, the patients were evaluated. If treatment was successful (≤1 attack/mo) or at the investigator's discretion, the patients entered a 3-month follow-up period. The patients with an average of >1 attack/month were eligible for further escalation to 2000 U and then 2500 U.
  
  
  RESULTS
  Twenty patients started at 1500 U; 13 were escalated to 2000 U, and 12 were escalated to 2500 U. Eighteen patients reported adverse events. Two patients reported 4 serious adverse events (cerebral cystic hygroma, laryngeal angioedema attack, anemia, and bile duct stone) that were considered by investigators to be unrelated to treatment. Notably, there were no systemic thrombotic events or discontinuations due to adverse events. Fourteen patients were treated successfully (70%), continued to the follow-up period at the investigator's discretion, or experienced a reduction in attacks of >1.0/month.
  
  
  CONCLUSIONS
  Dose escalation of nanofiltered C1 inhibitor (human) up to 2500 U was well tolerated and reduced attack frequency in the majority of patients.
authors.affiliation: Division of Immunology, Allergy, and Rheumatology, and Department of Internal Medicine, University of Cincinnati, Cincinnati, Ohio. Electronic address: Jonathan.Bernstein@uc.edu.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
authors.affiliation: Allergy, Asthma and Immunology Associates, Ltd, Scottsdale, Ariz.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Manning
authors.affiliation: Institute for Asthma and Allergy, Chevy Chase, Md.
authors.forename: Henry
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute for Asthma and Allergy, Wheaton, Md.
authors.forename: Martha V
authors.initials: MV
authors.lastname: White
authors.affiliation: Allergy Asthma & Dermatology Associates, Lake Oswego, Ore.
authors.forename: James
authors.initials: J
authors.lastname: Baker
authors.affiliation: AARA Research Center, Dallas, Tex.
authors.forename: William R
authors.initials: WR
authors.lastname: Lumry
authors.affiliation: Division of Rheumatology and Immunology, Winthrop University Hospital, Mineola, NY.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Davis-Lorton
authors.affiliation: Allergy and Asthma Research Group, Eugene, Ore.
authors.forename: Kraig W
authors.initials: KW
authors.lastname: Jacobson
authors.affiliation: Marycliff Allergy Specialists, Spokane, Wash.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Gower
authors.affiliation: Clinical Research for Broom and Schranz and Biostatistics for Fitts, ViroPharma Incorporated, Exton, Pa.
authors.forename: Colin
authors.initials: C
authors.lastname: Broom
authors.affiliation: Clinical Research for Broom and Schranz and Biostatistics for Fitts, ViroPharma Incorporated, Exton, Pa.
authors.forename: David
authors.initials: D
authors.lastname: Fitts
authors.affiliation: Clinical Research for Broom and Schranz and Biostatistics for Fitts, ViroPharma Incorporated, Exton, Pa.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schranz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D003174:Complement C1 Inactivator Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D050718:Complement C1 Inhibitor Protein; D003173:Complement C1s / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D003173:Complement C1s
keywords: Angioedema; C1 Esterase inhibitor; C1 INH; C1 INH-nf; C1 esterase inhibitor; Dose escalation; HAE; Hereditary angioedema; Nanofiltered C1 INH (human); Prophylaxis; Thrombotic events; Treatment