title: Safety of C1-esterase inhibitor in acute and prophylactic therapy of hereditary angioedema: findings from the ongoing international Berinert patient registry.
abstract: BACKGROUND
  The plasma-derived, pasteurized C1-inhibitor (C1-INH) concentrate, Berinert has a 4-decade history of use in hereditary angioedema (HAE), with a substantial literature base that demonstrates safety and efficacy. Thromboembolic events have rarely been reported with C1-INH products, typically with off-label use or at supratherapeutic doses.
  
  
  OBJECTIVE
  Active surveillance of safety and clinical usage patterns of pasteurized C1-inhibitor concentrate and the more recent pasteurized, nanofiltered C1-INH, with a particular interest in thromboembolic events.
  
  
  METHODS
  A registry was initiated in April 2010 at 27 US and 4 EU sites to obtain both prospective and retrospective safety and usage data on subjects who were administered C1-INH (Berinert).
  
  
  RESULTS
  As of May 10, 2013, data were available for 135 subjects and 3196 infusions. By subject, 67.4% were using C1-INH as on-demand therapy and 23.0% as both on-demand therapy and prophylactic administration. Approximately half of the infusions (49.5%) were administered for prophylaxis and >90% were given by the patient or a caregiver in the home setting. A total of 299 adverse events were reported, for an overall rate of 0.09 events per infusion with only 6 considered related to C1-INH. Two thromboembolic events were reported, both in patients with prothrombotic risk factors.
  
  
  CONCLUSIONS
  This large pool of real-world clinical usage data in HAE further supports the extensive safety profile of 2 Berinert formulations when used on demand and/or for prophylaxis in both home and health care settings. No evidence was found to suggest that Berinert is an independent, causative risk factor for thromboembolic events.
authors.affiliation: Mount Sinai Hospital, New York, NY.
authors.forename: Paula
authors.initials: P
authors.lastname: Busse
authors.affiliation: HAE Centre Denmark, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark.
authors.forename: Anette
authors.initials: A
authors.lastname: Bygum
authors.affiliation: CSL Behring, King of Prussia, Pa.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Edelman
authors.affiliation: AARA Research Center, Dallas, Tex.
authors.forename: William
authors.initials: W
authors.lastname: Lumry
authors.affiliation: CSL Behring GmbH, Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Machnig
authors.affiliation: Hemophilia Center Rhine Main GmbH, Mörfelden-Walldorf, Germany.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Martinez-Saguer
authors.affiliation: CSL Behring, King of Prussia, Pa. Electronic address: mikhail.rojavin@cslbehring.com.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Rojavin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D054179:Angioedemas, Hereditary / Q000188:drug therapy* / Q000517:prevention & control*; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012042:Registries; D013923:Thromboembolism / Q000139:chemically induced; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein
keywords: Berinert; C1-INH; On demand; Prophylaxis; Registry; Safety; Self administration; Thromboembolic events