Insights from the first 820 patients from the Brazilian Multicenter Registry of Hereditary Angioedema: the key role of genetic testing and targeted therapies.

Hereditary angioedema (HAE) is a rare autosomal dominant disorder with a prevalence of 1:50,000 individuals. Delayed diagnosis and deaths from asphyxia still occur. To identify knowledge and management gaps regarding clinical, genetic, and therapeutic aspects of HAE in Brazil, aiming to improve patient care and outcomes. A Brazilian multicenter HAE Registry was established, with patients' data included by treating physicians using the REDCap platform. Of the 820 HAE patients enrolled, 68.8% were female. Most (72.4%) presented HAE due to C1INH deficiency (HAE-C1INH), whereas 19.4% had HAE with normal C1INH caused by variants in the F12 gene (HAE-FXII). Onset of symptoms occurred earlier in HAE-C1INH as compared to HAE-FXII (mean 11.2 years versus 19.4 years, respectively), and time for diagnosis was shorter in patients younger than 18 years-old, as compared to those 18 years-old and older (mean 1.8 years versus 14.5 years, respectively). Regarding treatment, 52.8% received first-line on-demand therapies (Icatibant or plasma-derived C1INH). Only 4.8% used first-line options for long-term prophylaxis (LTP), such as lanadelumab or subcutaneous/intravenous pdC1INH. Attenuated androgens were used for LTP in 52% of patients, with adverse effects reported for 34.8%. Brazilian patients with HAE share common aspects with global patients, including predominance in women, and HAE-C1INH as the most common subtype. Available genetic testing allowed for identification of a notable proportion of HAE-FXII (19.4% of the patients). Despite recent advances, access to first-line therapies for long-term prophylaxis of HAE attacks remains limited.