D2.319 - Advancing Diagnosis and Management of Hereditary Angioedema in Brazil: Insights from the first 704 patients of a Multicenter Registry

In Brazil, there is a delay in HAE diagnosis of 10–15 years and fatalities from asphyxia still occur. The project project aimed to develop a Multicenter Registry for HAE patients in Brazil by the treating physicians, and to enhance HAE diagnosis among patients and their families, focusing on genetic testing.

A Brazilian registry for HAE was established, with data included in the REDCap platform by treating physicians.

Out of 704 patients, 66.3% were female. Among 14 deceased patients included in the Registry, 50% died from angioedema attacks. Of 692 responses out of 704 total, 82.8% reported relatives with confirmed HAE diagnoses. The majority of patients(78%) were diagnosed with HAE due to C1-INH deficiency (HAE-C1INH), with 117 having a SERPING1 gene variant identified, while 22% had HAE with normal C1-INH (HAE-nC1INH), linked to variants in the F12 gene. Symptomatic cases were higher in HAE-C1INH(94.5%) than in HAE-FXII(81.3%,p<0.001). Onset of symptoms was earlier in HAE-C1INH (mean:11.4 years) as compared to HAE-FXII (19.1 years, p<0.01). Triggers included psychological stress (HAE-C1INH 60.5%; HAE-FXII 53.7%,p=0,18), physical trauma (50.3% vs. 35.8%,p=0.004), and anxiety(42.9% vs. 30.9%,p=0.01). Combined oral contraceptives triggered attacks in 43.9% of HAE-FXII versus 11.6% of HAE-C1INH female patients (p<0.01). Approximately 30% of patients reported no identifiable triggers, underscoring disease unpredictability. Regarding treatment, 93.9% of symptomatic patients had received on-demand therapies, with 53.4% accessing first-line medications (Icatibant or pdC1-INH). Long-term prophylaxis was reported by 519 patients, but only 6.7% used first-line options (Lanadelumab, subcutaneous/intravenous C1-INH, or Berotralstat). Most relied on second-line therapies, including attenuated androgens (68.9%), which often caused adverse effects.

Brazilian HAE patients share common aspects with global cases, such as higher prevalence in women (1.97:1) and predominance of HAE-C1INH. Improved genetic diagnosis likely accounted for the higher frequency (28.3%) of HAE-nC1INH cases. Despite advancements, access to first-line therapies for long-term prophylaxis of HAE attacks remains limited.