Center for ALS and other Motor Neuron Disorders, Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Ambulanzpartner Soziotechnologie APST GmbH, Berlin, Germany.
Muscle Nerve. 2024 Sep;70(3):333-345. doi: 10.1002/mus.28182. Epub 2024 Jun 20.
INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1-ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient-reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany.
Sixteen SOD1-ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS-PR), as measured by the monthly change of the ALS functional rating scale-revised (ALSFRS-R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and Net Promoter Score (NPS).
Mean tofersen treatment was 11 months (6-18 months). ALS-PR showed a mean change of -0.2 (range 0 to -1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS-R. SVC was stable (mean 88%, range -15% to +28%). sNfL decreased in all patients except one heterozygous D91A-SOD1 mutation carrier (mean change of sNfL -58%, range -91 to +27%, p < .01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM-9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80).
Data from this EAP supported the clinical and sNfL response to tofersen in SOD1-ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.
简介/目的：在由 SOD1 突变引起的肌萎缩侧索硬化症（ALS）中，托法替布在 美国获得了加速批准，并可通过在美国以外的扩大准入计划（EAP）获得。这项多中心研究调查了托法替布治疗期间 EAP 中德国 16 名接受托法替布治疗至少 6 个月的 SOD1-ALS 患者的临床和患者报告结局（PRO）以及血清神经丝轻链（sNfL）。
分析了 16 名接受托法替布治疗至少 6 个月的 SOD1-ALS 患者。通过每月变化 ALS 功能评定量表修订版（ALSFRS-R）、肺活量（SVC）和 sNfL 来研究 ALS 进展率（ALS-PR）。PRO 包括自我评估医疗结局测量量表（MYMOP2）、药物治疗满意度问卷（TSQM-9）和净推荐值（NPS）。
托法替布的平均治疗时间为 11 个月（6-18 个月）。ALS-PR 平均变化为-0.2（范围 0 至-1.1），相对减少 25%。7 名患者的 ALSFRS-R 增加。SVC 稳定（平均 88%，范围-15%至+28%）。除一名杂合 D91A-SOD1 突变携带者外，所有患者的 sNfL 均下降（sNfL 平均下降 58%，范围-91%至+27%，p<.01）。MYMOP2 表明症状严重程度改善（n=10）或部分缓解感知（n=6）。TSQM-9 显示出很高的整体治疗满意度（平均 83，SD 16），尽管药物管理的便利性适中（平均 50，SD 27）。NPS 显示托法替布的推荐率非常高（NPS+80）。
这项 EAP 的数据支持 SOD1-ALS 中托法替布的临床和 sNfL 反应。PRO 表明患者对托法替布治疗的临床实践有较好的感知。
