背景:遗传性血管性水肿(HAE),一种罕见的疾病,以疼痛和反复出现的非过敏性肿胀发作为特征,是由C1抑制剂(C1INH)蛋白的缺乏或功能障碍引起的。全面的HAE管理计划可能需要长期预防(LTP)以及按需治疗,以帮助“使患者的生活正常化”,以便他们可以充分从事工作,学校,家庭,和休闲活动。
目的:本叙述性综述的主要目的是概述针对HAE的LTP的最新指南建议,并讨论临床考虑因素和药物管理方案。专注于C1INH。
方法:作者回顾了目前关于LTP和C1NH作用的相关HAE文献。
结果:急性HAE发作采用按需药物治疗;然而,人们一致认为,LTP应被常规考虑用于降低风险和预防未来发作.2017年世界变态反应组织/欧洲变态反应和临床免疫学会指南建议对所有HAE患者进行常规LTP评估,2020年HAE协会(HAEA)指南强调使用LTP的决定不应基于严格的标准。而是应该基于个体患者的需求。这两个指南都推荐C1INH作为LTP的一线/首选治疗,包括成人在内的一系列患者类型。儿童/青少年,和怀孕/哺乳期患者。HAEA还建议使用激肽释放酶抑制剂,lanadelumab,作为LTP的一线选项。用于LTP的HAE途径特异性药物与显著的安全性问题无关。
结论:血浆来源的C1INH在欧洲已经使用了40多年,并影响HAE途径中的多个靶标。C1INH已用于按需治疗和LTP。血浆衍生的C1INH的皮下制剂被批准用于LTP,并产生的功能性C1INH活性水平始终高于保护免受HAE攻击所需的阈值。LTP的其他途径特异性选择包括血浆激肽释放酶抑制剂,lanadelumab-flyo和berotralstat,批准用于年龄≥12岁的成人和儿科患者。C1INH被批准用于年龄≥6岁的成人和儿科患者。
结论:评估LTP的需求在临床医生和患者之间的持续对话中至关重要。因为疾病相关因素和患者偏好都可能随着时间的推移而改变。在LTP的可用选项中,血浆来源的C1INH是HAE患者广泛推荐的LTP一线选择,包括孕妇/哺乳期妇女和儿科患者(≥6岁)。
BACKGROUND: Hereditary angioedema (HAE), a rare disease that is characterized by painful and recurring non-allergic swelling episodes, is caused by the deficiency or dysfunction of C1 inhibitor (C1INH) protein. A comprehensive HAE management plan may require long-term prophylaxis (LTP) in addition to on-demand treatment to help \"normalize\" patients\' lives so that they may fully engage in work, school, family, and leisure activities.
OBJECTIVE: The main objective of this narrative review is to provide an overview of updated
guideline recommendations specific to LTP of HAE and discuss clinical considerations and pharmacologic management options, with a focus on C1INH.
METHODS: The authors reviewed relevant HAE literature for current recommendations regarding LTP and the role of C1NH.
RESULTS: Acute HAE attacks are treated with on-demand medication; however, there is a
consensus that LTP should routinely be considered for risk reduction and prevention of future episodes. The 2017 World Allergy Organization/European Academy of Allergy and Clinical Immunology
guidelines recommend that all patients with HAE be evaluated for LTP routinely and the 2020 HAE Association (HAEA)
guidelines emphasize that the decision to use LTP should not be based on rigid criteria, but rather should be based on individual patient needs. Both
guidelines recommend C1INH as first-line/preferred therapy for LTP in a range of patient types including adults, children/adolescents, and pregnant/lactating patients. The HAEA also recommends the kallikrein inhibitor, lanadelumab, as a first-line option for LTP. HAE pathway-specific agents for LTP have not been associated with notable safety concerns.
CONCLUSIONS: Plasma-derived C1INH has been available for 40+ years in Europe and impacts multiple targets within the HAE pathway. C1INH has been used for on-demand treatment and LTP. A subcutaneous formulation of plasma-derived C1INH is approved for LTP and produces functional C1INH activity levels consistently above the threshold needed for protection from HAE attacks. Other pathway-specific options for LTP include the plasma kallikrein inhibitors, lanadelumab-flyo and berotralstat, approved for adults and pediatric patients aged ≥12 years. C1INH is approved for adults and pediatric patients aged ≥6 years.
CONCLUSIONS: Assessing the need for LTP is vital in the ongoing dialogue between clinicians and patients, as both disease-related factors and patient preferences may change over time. Among available options for LTP, plasma-derived C1INH is the broadly recommended first-line option for LTP in patients with HAE, including pregnant/lactating women and pediatric patients (≥6 years).