Clinical profile and treatment outcomes in patients with hereditary angioedema with normal C1 esterase inhibitor()

BACKGROUND: Hereditary angioedema (HAE) is often caused by low serum levels or functional deficiency in C1 inhibitor (C1-INH); however, in some cases, C1-INH serum level and function are measured as normal (HAE-nl-C1INH). Management of HAE-nl-C1INH is similar to management of HAE with C1-INH deficiency, including on-demand therapy for angioedema attacks and, potentially, prophylaxis. Recombinant human C1 esterase inhibitor (rhC1-INH) is indicated for treatment of acute HAE attacks. This study assessed the clinical profile and treatment outcomes in an HAE-nl-C1INH population with a history of rhC1-INH treatment. METHODS: Medical records containing patient-reported outcomes from ten US treatment centers were analyzed retrospectively for medical history, angioedema attack characteristics, attack treatments, and clinical outcomes. RESULTS: Twenty-three patients were included, with wide US geographic representation. Most patients (87.0%) were female; median age was 36.0 years (range, 19–67 years). Of 20 patients with available data, 4 had their first angioedema attack during childhood (aged <12 years), 3 during adolescence (aged 12–17 years), and 13 during adulthood (aged 18–29 years, n = 7; aged ≥30 years, n = 6). Median age at HAE-nl-C1INH diagnosis was 31.5 years (range, 9–59 years). Previous failed treatments included high-dose antihistamines (n = 20) and corticosteroids (n = 20). Use of US Food and Drug Administration (FDA)–approved HAE therapy positively impacted patient-reported assessments of angioedema attacks. Most patients were taking rhC1-INH or lanadelumab as prophylaxis and icatibant or rhC1-INH for acute management. Most patients reported improved disease control with these therapies, including reductions in angioedema attack frequency and severity. Although most patients were receiving prophylactic therapy, availability of treatment for breakthrough attacks was important. CONCLUSION: Findings from this retrospective study support use of FDA-approved HAE medications for prophylaxis and acute treatment of HAE attacks in patients with HAE-nl-C1INH. Individualized HAE treatment regimens were needed to optimize therapeutic outcomes.