Dieu Duc Chu, Pernice Helena F, Muratovic Harisa, Wetzel Paul J, Barzen Gina, Wieder Nicolas W, Werhahn Stefanie M, Heidecker Bettina, Spethmann Sebastian, Hahn Katrin
Amyloidosis Center Charité Berlin (ACCB), Charité University Medicine, Berlin, Germany.
Department of Neurology, Charité University Medicine, Berlin, Germany.
Neurol Res Pract. 2025 Sep 12;7(1):65. doi: 10.1186/s42466-025-00428-6.
Hereditary transthyretin amyloidosis is a rapidly progressive and lethal disease. Thanks to the increasing number of disease-modifying treatments, prognosis has improved significantly. However, new challenges regarding treatment response and when to change treatment remain unanswered. The objective of this study was to evaluate rationales for treatment switches from the past and to formulate learnings for future management.
In this retrospective single center study, we analyzed real-world data of 13 patients with hereditary transthyretin amyloidosis undergoing single or multiple treatment switches before January 2024. Data involved demographic characteristics as well as reasons for treatment switches in a descriptive and exploratory manner. Available amyloid specific therapies during the study period included tafamidis 20 mg, tafamidis 61 mg, patisiran, inotersen and vutrisiran.
Switches from tafamidis 20 mg were most frequently due to disease progression (83.3%). Patisiran transitions predominantly occurred following vutrisiran's approval, driven by preference for subcutaneous administration and extended dosing intervals (65.0%). Two cases of switches from inotersen were both associated with severe adverse effects.
In this study, reasons for treatment switches were manifold, encompassing disease progression, the occurrence of adverse events, patient preferences and/or the availability of newly approved drugs. Hence, multidimensional consideration of these reasons remains pivotal in guiding the subsequent choice of medication in particular and managing hereditary transthyretin amyloidosis in general.
遗传性转甲状腺素蛋白淀粉样变性是一种快速进展的致命疾病。由于疾病修饰治疗的数量不断增加，预后有了显著改善。然而，关于治疗反应以及何时改变治疗的新挑战仍未得到解答。本研究的目的是评估过去治疗转换的理由，并为未来的管理制定经验教训。
在这项回顾性单中心研究中，我们分析了2024年1月之前接受单次或多次治疗转换的13例遗传性转甲状腺素蛋白淀粉样变性患者的真实世界数据。数据以描述性和探索性方式涉及人口统计学特征以及治疗转换的原因。研究期间可用的淀粉样蛋白特异性疗法包括20毫克他氟米特、61毫克他氟米特、帕替沙兰、依诺特辛和缬草素。
从20毫克他氟米特转换治疗最常见的原因是疾病进展（83.3%）。帕替沙兰的转换主要发生在缬草素获批之后，原因是对皮下给药和延长给药间隔的偏好（65.0%）。两例从依诺特辛转换治疗的病例均与严重不良反应有关。
在本研究中，治疗转换的原因是多方面的，包括疾病进展、不良事件的发生、患者偏好和/或新批准药物的可用性。因此，对这些原因进行多维度考虑对于指导后续的药物选择以及总体上管理遗传性转甲状腺素蛋白淀粉样变性仍然至关重要。
