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

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 cours...

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Autores principales: Levy, Donald, Caballero, Teresa, Hussain, Iftikhar, Reshef, Avner, Anderson, John, Baker, James, Schwartz, Lawrence B., Cicardi, Marco, Prusty, Subhransu, Feuersenger, Henrike, Pragst, Ingo, Manning, Michael E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499895/
https://www.ncbi.nlm.nih.gov/pubmed/32953229
http://dx.doi.org/10.1089/ped.2020.1143
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author Levy, Donald
Caballero, Teresa
Hussain, Iftikhar
Reshef, Avner
Anderson, John
Baker, James
Schwartz, Lawrence B.
Cicardi, Marco
Prusty, Subhransu
Feuersenger, Henrike
Pragst, Ingo
Manning, Michael E.
author_facet Levy, Donald
Caballero, Teresa
Hussain, Iftikhar
Reshef, Avner
Anderson, John
Baker, James
Schwartz, Lawrence B.
Cicardi, Marco
Prusty, Subhransu
Feuersenger, Henrike
Pragst, Ingo
Manning, Michael E.
author_sort Levy, Donald
collection PubMed
description 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.
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spelling pubmed-74998952020-09-18 Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema Levy, Donald Caballero, Teresa Hussain, Iftikhar Reshef, Avner Anderson, John Baker, James Schwartz, Lawrence B. Cicardi, Marco Prusty, Subhransu Feuersenger, Henrike Pragst, Ingo Manning, Michael E. Pediatr Allergy Immunol Pulmonol Original Research 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. Mary Ann Liebert, Inc., publishers 2020-09-01 2020-09-16 /pmc/articles/PMC7499895/ /pubmed/32953229 http://dx.doi.org/10.1089/ped.2020.1143 Text en © Donald Levy et al., 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Levy, Donald
Caballero, Teresa
Hussain, Iftikhar
Reshef, Avner
Anderson, John
Baker, James
Schwartz, Lawrence B.
Cicardi, Marco
Prusty, Subhransu
Feuersenger, Henrike
Pragst, Ingo
Manning, Michael E.
Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title_full Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title_fullStr Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title_full_unstemmed Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title_short Long-Term Efficacy of Subcutaneous C1 Inhibitor in Pediatric Patients with Hereditary Angioedema
title_sort long-term efficacy of subcutaneous c1 inhibitor in pediatric patients with hereditary angioedema
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499895/
https://www.ncbi.nlm.nih.gov/pubmed/32953229
http://dx.doi.org/10.1089/ped.2020.1143
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