Hooi James K Y, Wong Jane C Y, Li Philip H
Division of Rheumatology & Clinical Immunology, Department of Medicine,University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Department of Medicine, University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Expert Opin Biol Ther. 2025 Jul;25(7):703-710. doi: 10.1080/14712598.2025.2512128. Epub 2025 May 26.
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of subcutaneous and/or submucosal swelling (angioedema). Current HAE-specific medications primarily focus on either inhibiting plasma bradykinin or kallikrein, or replacing C1-esterase inhibitor, but they are frequently limited in efficacy and accessibility. In contrast, Factor XII (FXII) inhibitors may provide a novel therapeutic approach by targeting the contact system at an upstream level, potentially addressing some of these limitations.
This review explores the role of FXII in HAE and assesses FXII inhibition as a promising prophylactic treatment strategy. By synthesizing findings from both preclinical and clinical studies and real-world observational studies, the review highlights the efficacy, safety, and practical benefits of FXII inhibitors, such as garadacimab.
FXII inhibition represents a promising new strategy for HAE management and may address current unmet needs in prophylactic therapies. The early experiences of garadacimab highlights FXII as a viable and druggable target, paving the way for broader applications in bradykinin-mediated disorders. Despite its potential, uncertainties remain regarding long-term safety, cost, and accessibility. Future research will help redefine the role of FXII inhibition in advancing personalized care and improving the quality of life for patients with HAE.
遗传性血管性水肿(HAE)是一种罕见的遗传性疾病,其特征为皮下和/或粘膜下反复肿胀发作(血管性水肿)。目前针对HAE的特异性药物主要集中在抑制血浆缓激肽或激肽释放酶,或替代C1酯酶抑制剂,但它们的疗效和可及性常常受到限制。相比之下,凝血因子XII(FXII)抑制剂可能通过在上游水平靶向接触系统提供一种新的治疗方法,有可能解决其中一些限制。
本综述探讨了FXII在HAE中的作用,并评估了FXII抑制作为一种有前景的预防性治疗策略。通过综合临床前和临床研究以及真实世界观察性研究的结果,本综述强调了FXII抑制剂(如加拉西单抗)的疗效、安全性和实际益处。
FXII抑制是HAE管理的一种有前景的新策略,可能解决预防性治疗中当前未满足的需求。加拉西单抗的早期经验突出了FXII作为一个可行且可成药的靶点,为在缓激肽介导的疾病中更广泛的应用铺平了道路。尽管有其潜力,但在长期安全性、成本和可及性方面仍存在不确定性。未来的研究将有助于重新定义FXII抑制在推进个性化医疗和改善HAE患者生活质量方面的作用。