Department of Neurology, Friedrich-Baur-Institute, LMU Clinics Munich, Munich, Germany.
Department of Neurology, Center for Lysosomal and Metabolic Diseases, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Eur J Neurol. 2024 Sep;31(9):e16383. doi: 10.1111/ene.16383. Epub 2024 Jun 14.
Two novel enzyme replacement therapies (ERTs), studied in phase 3 trials in late-onset Pompe patients, reached marketing authorization by the European Medicines Agency in 2022 and 2023. The European Pompe Consortium (EPOC) updates and extends the scope of the 2017 recommendations for starting, switching and stopping ERT.
The European Pompe Consortium consists of 25 neuromuscular and metabolic experts from eight European countries. This update was performed after an in-person meeting, three rounds of discussion and voting to provide a consensus recommendation.
The patient should be symptomatic, that is, should have skeletal muscle weakness or respiratory muscle involvement. Muscle magnetic resonance imaging findings showing substantial fat replacement can support the decision to start in a patient-by-patient scenario. Limited evidence supports switching ERT if there is no indication that skeletal muscle and/or respiratory function have stabilized or improved during standard ERT of 12 months or after severe infusion-associated reactions. Switching of ERT should be discussed on a patient-by-patient shared-decision basis. If there are severe, unmanageable infusion-associated reactions and no stabilization in skeletal muscle function during the first 2 years after starting or switching treatment, stopping ERT should be considered. After stopping ERT for inefficacy, restarting ERT can be considered. Six-monthly European Pompe Consortium muscle function assessments are recommended.
The triple-S criteria on ERT start, switch and stop include muscle magnetic resonance imaging as a supportive finding and the potential option of home infusion therapy. Six-monthly long-term monitoring of muscle function is highly recommended to cover insights into the patient's trajectory under ERT.
两种新型酶替代疗法(ERT)在晚期庞贝病患者的 3 期临床试验中进行了研究,并于 2022 年和 2023 年获得了欧洲药品管理局的营销授权。欧洲庞贝病联合会(EPOC)更新并扩展了 2017 年开始、转换和停止 ERT 的建议范围。
欧洲庞贝病联合会由来自 8 个欧洲国家的 25 名神经肌肉和代谢专家组成。本次更新是在一次现场会议、三轮讨论和投票后完成的,旨在提供共识建议。
患者应该有症状,即应该有骨骼肌无力或呼吸肌受累。肌肉磁共振成像显示大量脂肪替代的发现可以支持在患者个体情况下开始治疗的决策。如果在标准 ERT 12 个月或严重输注相关反应后没有迹象表明骨骼肌和/或呼吸功能稳定或改善,有限的证据支持转换 ERT。ERT 的转换应基于患者个体的共享决策进行讨论。如果在开始或转换治疗后的前 2 年内出现严重、无法控制的输注相关反应且骨骼肌功能没有稳定,应考虑停止 ERT。如果因无效而停止 ERT,可以考虑重新开始 ERT。建议每 6 个月进行一次欧洲庞贝病联合会肌肉功能评估。
ERT 开始、转换和停止的三重-S 标准包括肌肉磁共振成像作为支持性发现和潜在的家庭输注治疗选择。强烈建议每 6 个月进行一次长期肌肉功能监测,以了解 ERT 下患者的轨迹。