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儿童和青少年遗传性血管性水肿(HAE):新的治疗选择

Hereditary angioedema (HAE) in children and adolescents: New treatment options.

作者信息

Fasshauer Maria, Wedi Bettina

机构信息

Klinikum St. Georg Leipzig, Clinic for Pediatrics and Adolescent Medicine, ImmunDefektCentrum Leipzig (IDCL), Leipzig, and.

Hannover Medical School (MHH), Department of Dermatology, Allergology and Venereology, Interdisciplinary Allergy Center of the MHH, Treatment Center for Hereditary Angioedema of the MHH, Hannover, Germany.

出版信息

Allergol Select. 2024 Oct 30;8:336-345. doi: 10.5414/ALX02532E. eCollection 2024.

DOI:10.5414/ALX02532E
PMID:39502954
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11536504/
Abstract

Modern management of hereditary angioedema (HAE) due to reduced C1 inhibitor (C1-INH) function or concentration (HAE-C1-INH) focuses on individualized therapeutic strategies to address the specific needs of children and adolescents as well as the severity of the disease. Psychosocial factors such as the burden of disease and therapy on quality of life and participation play an important role. New medications have already significantly improved the prognosis and health related quality of life in HAE patients, but not all of these therapies have yet been approved for children. Further treatment options that inhibit bradykinin effects are currently being investigated. They target factor XIIa, prekallikrein, plasma kallikrein, or the bradykinin B2 receptor. Modern research focuses on oral options or long-acting parenteral therapy approaches to further optimize care and, in particular, the needs of children. There are also initial developments in the field of gene therapy, which could represent a causal treatment option for HAE in the future. This article focuses on the presentation and treatment of HAE type I (reduced C1-INH concentration) and HAE type II (impaired C1-INH function) in children and adolescents. Acquired AE and HAE with normal C1-INH are rare in the pediatric age group and are not discussed in detail here.

摘要

由于C1抑制物(C1-INH)功能或浓度降低所致遗传性血管性水肿(HAE-C1-INH)的现代管理侧重于个体化治疗策略,以满足儿童和青少年的特殊需求以及疾病的严重程度。诸如疾病负担以及治疗对生活质量和参与度的影响等社会心理因素起着重要作用。新药物已显著改善了HAE患者的预后和健康相关生活质量,但并非所有这些疗法都已获批用于儿童。目前正在研究抑制缓激肽作用的其他治疗选择。它们的靶点是因子XIIa、前激肽释放酶、血浆激肽释放酶或缓激肽B2受体。现代研究聚焦于口服药物或长效肠外治疗方法,以进一步优化治疗,尤其是满足儿童的需求。基因治疗领域也有初步进展,这可能在未来成为HAE的一种病因性治疗选择。本文重点介绍儿童和青少年I型HAE(C1-INH浓度降低)和II型HAE(C1-INH功能受损)的表现及治疗。获得性血管性水肿和C1-INH正常的HAE在儿童年龄组中罕见,本文对此不作详细讨论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/7b62cb95eff1/allergologieselect-8-336-04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/ccc2c88aeea7/allergologieselect-8-336-01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/962a6c8040e7/allergologieselect-8-336-02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/bc96cfb6fb57/allergologieselect-8-336-03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/7b62cb95eff1/allergologieselect-8-336-04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/ccc2c88aeea7/allergologieselect-8-336-01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/962a6c8040e7/allergologieselect-8-336-02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/bc96cfb6fb57/allergologieselect-8-336-03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb0f/11536504/7b62cb95eff1/allergologieselect-8-336-04.jpg

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N Engl J Med. 2024 Jul 4;391(1):32-43. doi: 10.1056/NEJMoa2314192. Epub 2024 May 31.
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Efficacy and Safety of Donidalorsen for Hereditary Angioedema.Donidalorsen 治疗遗传性血管性水肿的疗效和安全性。
N Engl J Med. 2024 Jul 4;391(1):21-31. doi: 10.1056/NEJMoa2402478. Epub 2024 May 31.
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CRISPR-Cas9 In Vivo Gene Editing of for Hereditary Angioedema.CRISPR-Cas9 体内基因编辑治疗遗传性血管性水肿。
N Engl J Med. 2024 Feb 1;390(5):432-441. doi: 10.1056/NEJMoa2309149.
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Epidemiology and treatment of children with hereditary angioedema in Germany: A retrospective database study.德国遗传性血管性水肿患儿的流行病学与治疗:一项回顾性数据库研究。
Clin Transl Allergy. 2023 Nov;13(11):e12313. doi: 10.1002/clt2.12313.
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Lanadelumab in Patients 2 to Less Than 12 Years Old With Hereditary Angioedema: Results From the Phase 3 SPRING Study.Lanadelumab用于2至未满12岁遗传性血管性水肿患者:3期SPRING研究结果
J Allergy Clin Immunol Pract. 2024 Jan;12(1):201-211.e6. doi: 10.1016/j.jaip.2023.09.009. Epub 2023 Sep 18.
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STAR-0215 is a Novel, Long-Acting Monoclonal Antibody Inhibitor of Plasma Kallikrein for the Potential Treatment of Hereditary Angioedema.STAR-0215是一种新型长效单克隆抗体血浆激肽释放酶抑制剂,用于遗传性血管性水肿的潜在治疗。
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Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.加拉西班单抗治疗遗传性血管性水肿预防的疗效和安全性(VANGUARD):一项全球、多中心、随机、双盲、安慰剂对照的 3 期临床试验。
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