Abdominal Presentation of Acute Attacks of Hereditary Angioedema and Efficacy of Recombinant C1 Inhibitor in Symptom Resolution: 339

Purpose: Hereditary angioedema (HAE) is a genetic disorder caused by a deficiency in C1 esterase inhibitor (C1INH) characterized by recurrent attacks of edema, frequently affecting the gastrointestinal (GI) tract. Abdominal attack symptoms of disabling pain, nausea, vomiting, and diarrhea are caused by a partial or complete bowel obstruction. Though self-limited, untreated attacks typically worsen over the course of 24 hours before resolving in two to three days. Undiagnosed patients frequently undergo unnecessary surgery. The aim of the current analysis was to evaluate the clinical presentation of abdominal HAE attacks and symptom resolution following treatment with recombinant human C1 esterase inhibitor (rhC1INH). Methods: HAE patients presenting with acute attacks were treated with rhC1INH (50 IU/kg up to 4200 IU) in an open-label design. Overall attack severity and severity of individual abdominal symptoms (abdominal pain, nausea) were assessed using 100 mm visual analog scales (VAS) as minimal (VAS <20 mm), moderate (VAS ≥20 mm to <50 mm) or severe (VAS ≥50 mm). Onset of symptom relief was defined as a reduction in the overall severity VAS by >20 mm. Assessments were performed for abdominal attacks as patient's primary attack location among the first five treated attacks for each patient. Results: A total of 24 patients presented for 51 attacks with abdominal symptoms as their primary attack location. Prior to treatment, abdominal pain was rated as severe for 96% of attacks and the majority of attacks (69%) were associated with severe nausea. The median (25th-75th percentiles) overall attack severity at Baseline was 88 (74-96) mm. The median (95% confidence interval) time to onset of symptom relief for all abdominal attacks was 62 (60, 77) minutes, with median times of 68, 60, 75, 84, and 44 minutes for abdominal attacks occurring as attacks 1, 2, 3, 4, and 5, respectively. By 4 hours following treatment, only one attack was associated with severe abdominal pain. The median (25th-75th percentiles) overall attack severity at 4 hours was 5 (1-20) mm. Overall, rhC1INH was well tolerated, with a favorable safety profile. Conclusion: HAE patients may present to gastroenterologists with abdominal angioedema attacks associated with severe GI symptoms. It is important for gastroenterologists to be aware of acute attacks of HAE for consideration in the differential diagnosis of recurrent severe abdominal pain. Treatment with rhC1INH was effective in improving symptoms of abdominal attacks, with a positive safety profile observed after both single and repeated treatments. Disclosure: H. Henry Li: Research support from Pharming for participation in the clinical trial Marc Riedl: Research support from Pharming for participation in the clinical trial Jonathan Bernstein: Research support from Pharming for participation in the clinical trial Yun Hardiman: Employee of Santarus, Inc Anurag Relan: Employee of Pharming.