Patient-reported disease burden and health care utilization of HAE-nl-C1INH: insights from a real-world survey

Hereditary angioedema (HAE), a rare genetic disorder, is classified into 3 types: Type 1 (low C1 esterase inhibitor [C1-INH]), Type 2 (dysfunctional C1-INH), and HAE-nl-C1INH (normal C1-INH levels). This study aimed to compare characteristics among individuals with HAE Type 1/2 and HAE-nl-C1INH. A cross-sectional online survey was conducted (June 2020-September 2021) among adults with HAE to capture various patient-specific data and health care utilization. Statistical analyses included Fisher exact test, t test, and odds ratios (OR) with 95% confidence intervals (CI). Eighty-nine participants were included (HAE Type 1/2, n = 44; HAE-nl-C1INH, n = 45). No significant differences in demographics, treatment characteristics, and HAE triggers were observed between groups. Participants with HAE-nl-C1INH were less likely to be diagnosed before 18 years of age (4% vs. 32%; OR, 0.10; 95% CI, 0.02-0.50) and had higher odds of experiencing frequent HAE attacks (47% vs. 14%; OR, 5.5; 95% CI, 2.0-15.7) than those with HAE Type 1/2. Participants with HAE-nl-C1INH also had increased odds of orofacial-laryngeal swelling (31% vs. 16%; OR, 2.3; 95% CI, 1.1-4.7), more frequent doctor visits (> 1 visit/month: 31% vs. 11%; OR, 3.5; 95% CI, 1.1-10.8), and more concomitant conditions (93% vs. 77%; OR, 3.8; 95% CI, 1.6-9.2). The total health-related quality of life score was significantly worse in participants with HAE-nl-C1INH (53.6 vs. 38.2; p = 0.0001). Participants with HAE-nl-C1INH experience a significantly greater disease burden than those with HAE Type 1/2, emphasizing the need for improved diagnosis, targeted treatment strategies, and a deeper understanding of the prevalence and pathophysiology of HAE-nl-C1INH.