Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema

Abstract

Background: Hereditary angioedema (HAE) due to C1 inhibitor (C1INH) deficiency is characterized by recurrent attacks of edema of the skin and mucosal tissues. Symptoms usually present during childhood (mean age at first attack, 10 years). Earlier symptom onset may predict a more severe disease course. Subcutaneous (SC) C1INH is indicated for routine prophylaxis to prevent HAE attacks in adolescents and adults. We analyzed the long-term efficacy of C1INH (SC) in subjects £17 years old treated in an open-label extension (OLE) of the pivotal phase III Clinical Study for Optimal Management of Preventing Angioedema with Low-Volume Subcutaneous C1 Inhibitor Replacement Therapy (COMPACT) trial. Methods: Eligible subjects (age ‡6 years, with ‡4 attacks over 2 consecutive months before entry into the OLE or placebo-controlled COMPACT trial) were treated with C1INH (SC) 40 or 60 IU/kg twice weekly for 52-140 weeks. Subgroup analyses by age (£17 vs. >17 years) were performed for key efficacy endpoints. Results: Ten subjects were £17 years old [mean (range) age, 13.3 (8-16) years, 3 subjects <12 years old; exposure range, 51-133 weeks]. All 10 pediatric subjects experienced ‡50% reduction (mean, 93%) in number of attacks versus the prestudy period, with a 97% reduction in the median number of attacks/month (0.11). All subjects had <1 attack/4-week period and 4 had <1 attack/year (1 subject was attack free). No subject discontinued treatment due to a treatment-related adverse event. Conclusions: Data from pediatric subjects treated with C1INH (SC) for up to 2.55 years and adult subjects revealed similar efficacy. C1INH (SC) is effective and well tolerated as long-term prophylaxis in children, adolescents, and adults with HAE.

Hereditary angioedema: a disease seldom diagnosed by pediatricians

“… 1 , 37 In 2017, the pdC1-INH for subcutaneous use, Haegarda®, was approved by the FDA (US Food and Drug Administration) for long-term prophylaxis, at a dose of 60 U/kg every 2 weeks in adolescents. 40 A recent study showed the efficacy and safety of the medication also in children. 40 However, its use has not yet been approved in Brazil.…”

“… 40 A recent study showed the efficacy and safety of the medication also in children. 40 However, its use has not yet been approved in Brazil.…”

“…PdC1-INH (Haegarda®) and lanadelumab (Takhzyro®) have significantly changed long-term prophylaxis, since both are safe and the route of administration is subcutaneous. 39 , 40 However, additional studies are still needed to evaluate the effectiveness and safety in younger children. Clinical studies are being carried out with oral medications, which could further change the treatment scenario for these patients.…”

Preventive Treatment of Hereditary Angioedema: A Review of Phase III Clinical Trial Data for Subcutaneous C1 Inhibitor and Relevance for Patient Management

“…Levy et al 55 reported an analysis of safety and efficacy data from 10 pediatric patients (mean age, 13.3 years; range, 8-16 years) who participated in the COMPACT OLE. Five were treated with C1INH(SC) 40 IU/kg SC, and 5 were treated with C1INH(SC) 60 IU/kg SC.…”

A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema

“…4,8 While on rare occasions attacks may occur in the first year of life, there has been a single documented case of an HAE attack occurring in utero in a mother who had a facial attack while in active labor. 9,10 The mean age of the first HAE episode is 10 years, and approximately 40% of patients experience their first episode by age 5 years. 3,4,8 The onset of clinical symptoms at an early age is associated with a more severe disease course, including more HAE episodes per year and more hospitalizations for HAE-associated symptoms.…”