Hereditary angioedema with normal C1 inhibitor: Clinical characteristics and treatment response with plasma-derived human C1 inhibitor boncentrate (Berinert) in a French cohort

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 Angioedeme [COBRA] registry of HAE patients with everyday use of Berinert<sup></sup>) 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<sup></sup>-treated attacks, the majority occurring in the laryngeal and abdominal regions. Efficacy assessment of Berinert<sup></sup> was available for 38 of 78 documented Berinert<sup></sup>-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<sup></sup> may be a safe and efficacious treatment option for the majority of HAE patients.

Available from: https://link.springer.com/article/10.1684/ejd.2016.2948