Abstract
Hereditary angioedema (HAE) is a rare genetic disorder characterized by potentially life-threatening episodes of swelling. Most HAE cases are caused by deficient (type I) or dysfunctional (type II) C1-esterase inhibitor (C1-INH) protein. However, some patients present with a subtype of HAE that is associated with normal plasma levels of functional C1-INH protein and complement component 4 (HAE-nC1INH). Treatment of HAE-nC1INH is driven by clinical experience as robust clinical trial data to inform treatment decisions are lacking in this population. This retrospective case series assessed clinical features and treatment outcomes in 15 patients with HAE-nC1INH who initiated long-term prophylaxis with oral berotralstat 150 mg once daily as part of their disease management pathway. Most patients were female (93%), with a median age of 49 years. All patients experienced abdominal swelling attacks. On average, patients tried a mean of 4 different treatments for their HAE, including berotralstat. Although most patients associated prophylactic and on-demand medications that target the bradykinin pathway with improvements in the frequency and/or severity of attacks, treatment outcomes varied considerably between patients, highlighting the importance of a personalized approach to disease management. In this case series, berotralstat was an effective prophylactic treatment option in most patients with HAE-nC1INH. Further studies are required to demonstrate the potential efficacy, safety, and impact on quality of life of currently approved HAE therapies in patients with HAE-nC1INH.