A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema.

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology 2019 Aug

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Patients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health-related quality of life (HRQoL) outcomes of C1 inhibitor (C1-INH) prophylaxis (intravenously administered) in patients aged 6-11 years were investigated. Eligible patients were enrolled in a randomized, single-blind, crossover, phase 3 trial. After a 12-week baseline observation period (BOP), patients received 500 or 1000 U C1-INH, twice weekly, for 12 weeks before crossing over to the alternate dose for 12 weeks. The primary efficacy end-point was the monthly normalized number of angioedema attacks (NNA). HRQoL was assessed using the EuroQoL 5-dimensional descriptive system youth version and visual analog scale (EQ-VAS). Twelve randomized patients had a median (range) age of 10.0 (7-11) years. Mean (SD) percentage reduction in monthly NNA from BOP was 71.1% (27.1%) with 500 U and 84.5% (20.0%) with 1000 U C1-INH. Mean (SD) within-patient difference (-0.4 [0.58]) for monthly NNA with both doses was significant (P = 0.035 [90% CI, -0.706 to -0.102]). Cumulative attack severity, cumulative daily severity, and number of acute attacks treated were reduced. No serious adverse events or discontinuations occurred. Mean EQ-VAS change from BOP to week 9 of treatment (500 U C1-INH, 10.4; 1000 U C1-INH, 21.6) was greater than the minimal important difference, indicating a meaningful HRQoL change. C1-INH prophylaxis was effective, safe, and well tolerated in children aged 6-11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1-INH. ClinicalTrials.gov identifier NCT02052141. © 2019 The Authors. Pediatric Allergy and Immunology Published by John Wiley & Sons Ltd.

Citation

Emel Aygören-Pürsün, Daniel F Soteres, Sandra A Nieto-Martinez, Jim Christensen, Kraig W Jacobson, Dumitru Moldovan, Arthur Van Leerberghe, Yongqiang Tang, Peng Lu, Moshe Vardi, Jennifer Schranz, Inmaculada Martinez-Saguer. A randomized trial of human C1 inhibitor prophylaxis in children with hereditary angioedema. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2019 Aug;30(5):553-561