The US HAEA Scientific Registry: Hereditary Angioedema Demographics, Disease Severity, and Comorbidities.

BACKGROUND: Hereditary Angioedema (HAE) and idiopathic non-histaminergic angioedema (INHA) are ultra-rare diseases whose natural histories and comorbidities are incompletely understood.

OBJECTIVE: To develop a national patient-centric registry to address these deficiencies in our knowledge and improve our ability to assess the real-world impact of therapeutic interventions.

METHODS: Data from members of the US HAE Association were collected into an online registry between 2009 and April 7, 2021. Cohorts were categorized by reported physician diagnosis. Patient reported data were collected using a series of questionnaires. Demographic, natural history, and family history outcomes of the HAE due to C1-inhibitor deficiency (HAE-C1INH) participants were compared to the combined HAE with normal C1-inhibitor (HAE-nl-C1INH) plus INHA group. The prevalence of comorbid conditions in HAE-C1INH group were compared to the general United States population.

RESULTS: 485 HAE-C1INH, 26 HAE-nl-C1INH and 70 INHA participants were included in the analysis. Delay to diagnosis was shorter in HAE-C1INH (5 vs 11 years), but both showed decreasing delays over time. Differences in attack frequency and location were seen between the groups. Morbidity surrogates including Emergency Department visits, hospitalizations, unnecessary abdominal surgeries and intubations were strikingly high as was mortality with 36.9% of HAE-C1INH and 15.4% of HAE-nl-C1INH participants reporting family members who died from a HAE attack. Females with HAE-C1INH showed a significant increase in the prevalence of depression, sleep disorders, kidney disease, anemia, and hepatitis. Cardiovascular comorbidities were significantly reduced in the HAE-C1INH group.

CONCLUSION: The US HAEA Scientific Registry provides a mechanism to enhance our knowledge of HAE and INHA.