Real-World Safety and Effectiveness of Icatibant in Patients With Hereditary Angioedema (HAE): Post-Marketing Surveillance in Japan.

Hereditary angioedema (HAE) is a rare, autosomal dominant, life-threatening disease characterized by recurrent attacks of swelling of the face, upper airway, gastrointestinal tract, limbs, and/or genitalia. Genetic mutations of the SERPING1 gene encoding the C1-inhibitor (C1-INH) plasma protein are associated with HAE-C1INH. HAE is also observed in patients with normal C1-INH (HAE-nC1INH). Icatibant is a selective bradykinin B2 receptor antagonist for treatment of acute attacks of HAE. Here we report safety and effectiveness data from a post-marketing, open-label, multicenter observational study of icatibant conducted in Japan (ClinicalTrials.gov ID: NCT04057131). Patients with HAE in Japan who initiated icatibant between November 2018 and June 2020 were enrolled; surveillance was completed in April 2023. In the Safety Analysis Set (n = 155), most patients were women (n = 116, 74.84%) and HAE types included HAE-C1INH-Type 1 (n = 83, 53.55%), HAE-C1INH-Type 2 (n = 9, 5.81%), unclassified HAE-C1INH (n = 16, 10.32%), and HAE-nC1INH (n = 22, 14.19%). Overall, 19 patients (12.26%) experienced adverse drug reactions (ADRs), most of which were mild in severity (n = 18, 11.61%). The most common ADRs were general disorders and administration site conditions (n = 18, 11.61%). No serious ADRs or ADRs of special interest other than hypersensitivity and injection site reaction were reported. In the Effectiveness Analysis Set (n = 100), 97 patients (97.00%) received 30 mg of icatibant. Among 417 HAE attacks, 234 were treated with icatibant alone and 48 with icatibant plus other. Among attacks treated with icatibant alone, median (interquartile range) time to first symptom relief was 60.0 (30.0-270.0) min, and median time to complete resolution of symptoms was 710.0 (148.5-1440.0) min. In conclusion, in this study of the real-world use of icatibant, no new safety concerns were reported. Icatibant was effective in providing early symptom relief for HAE attacks across a broad spectrum of patients, including patients with HAE-nC1INH, who were not included in previous clinical trials.