Safety and efficacy of C1 esterase inhibitor for acute attacks in children with hereditary angioedema

Background: Human plasma-derived nanofiltered C1 esterase inhibitor (C1 INH-nf) is used to treat acute angioedema attacks in patients with hereditary angioedema (HAE), but data regarding use in children are sparse. Methods: Patients 2 to <12 years of age, body weight ≥10 kg, with a diagnosis of HAE type I or II, were recruited for a multicenter open-label trial. Patients were recruited into 2 weight categories (10-25 kg, >25 kg). Each weight category included 2 dosing levels: C1 INH-nf (500 units [U], 1000 U) and C1 INH-nf (1000 U, 1500 U), respectively. Patients experiencing an angioedema attack were given a single intravenous dose. Primary efficacy end-point was the onset of unequivocal relief of the defining symptom within 4 h following initiation of C1 INH-nf treatment. Results: Nine children were treated: 3 (10-25 kg) received 500 U; 3 (>25 kg) received 1000 U; and 3 (>25 kg) received 1500 U. The lower weight/higher dose category (10-25 kg, 1000 U) was not successfully enrolled. All patients completed the study. Most angioedema attacks (n = 5) were abdominal. All patients met the primary end-point; median time to unequivocal symptom relief was 0.5 (range: 0.25-2.5) h. Doses of C1 INH-nf ranged from 20.8 to 51.9 U/kg. Conclusions: Treatment of a single angioedema attack with C1 INH-nf doses of 500 U (in patients 10-25 kg), 1000 U, and 1500 U (in patients >25 kg) were well tolerated. Doses of C1 INH-nf <1000 U may be appropriate in some pediatric patients.