title: Hereditary angioedema with normal C1 inhibitor: clinical characteristics and treatment response with plasma-derived human C1 inhibitor concentrate (Berinert®) in a French cohort.
abstract: Hereditary angioedema (HAE) is a rare genetic disorder characterised by episodes of swelling without urticaria. Berinert® (CSL Behring) is a plasma-derived human C1 inhibitor (C1-INH) concentrate, approved for the treatment of HAE with C1-INH deficiency (C1-INH-HAE), however, it is often used off-label in Europe to treat HAE with normal C1-INH. To report the clinical characteristics of patients with HAE with normal C1-INH (with F12 gene mutation; FXII-HAE) or of unknown origin (U-HAE), and their response to Berinert®. Data from 2007 to 2016 (obtained retrospectively from the French Cohort BeRinert Angiœdème [COBRA] registry of HAE patients with everyday use of Berinert®) were analysed; no control group was included. Diagnostic criteria for FXII-HAE and U-HAE included a normal C1-INH antigenic level and function and refractoriness to high-dose antihistamines. For FXII-HAE, diagnosis also included F12 gene mutation, and U-HAE a positive family history for the disease. To date, 28 patients with FXII-HAE or U-HAE were identified (mean age: 27 years; first angioedema attack at 19.8 years; 85.7% female) with 78 documented Berinert®-treated attacks, the majority occurring in the laryngeal and abdominal regions. Efficacy assessment of Berinert®was available for 38 of 78 documented Berinert®-treated attacks; 22 improved within 60 minutes of treatment initiation, nine within 60-180 minutes, four after 180 minutes, and three showed no improvement. No severe or serious adverse effects were reported. Data to date suggest that Berinert®may be a safe and efficacious treatment option for the majority of HAE patients.
authors.affiliation: Univ. Grenoble Alpes, Joint unit 1036 INSERM-CEA-CNRS, CREAK, Department of Internal Medicine, PPMGC, CHU Grenoble, Grenoble, France, National Reference Centre for Angioedema, CREAK, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
authors.affiliation: Univ. Grenoble Alpes, Joint unit 1036 INSERM-CEA-CNRS, CREAK, Department of Internal Medicine, PPMGC, CHU Grenoble, Grenoble, France, National Reference Centre for Angioedema, CREAK, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boccon-Gibod
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Endocrine Gynaecology, Paris Descartes University, University Hospital Centre, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Gompel
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Floccard
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Department of Dermatology, CHU Angers, Angers, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Department of Internal Medicine, CH Niort, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Blanchard-Delaunay
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Université Lille Nord de France, Department of Internal Medicine, National Reference Centre for Autoimmune and Systemic Rare Diseases, Hospital Claude-Huriez, CHRU Lille, France.
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.affiliation: National Reference Centre for Angioedema, CREAK, France, Department of Internal Medicine, Saint Antoine University Hospital, AP-HP, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fain
mesh_terms: D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D050718:Complement C1 Inhibitor Protein / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D005174:Factor XII / Q000235:genetics; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D050718:Complement C1 Inhibitor Protein; D005174:Factor XII
keywords: Berinert®; C1 inhibitor; drug safety; hereditary angioedema; off label; pharmaco-epidemiological; registry