Tofersen 临床和患者报告结局及神经丝反应

肌肉神经。2024年9月；70(3):333-345。

doi: 10.1002/mus.28182。电子版发布日期：2024年6月20日。

SOD1相关ALS患者接受托弗森治疗期间的临床和患者报告结局及神经丝反应——一项为期18个月的多中心观察性研究

摘要

引言/目的：在SOD1突变引起的肌萎缩侧索硬化症(ALS) (SOD1-ALS)中，托弗森在美国获得了加速批准，并可通过美国以外的扩展获取计划(EAP)获得。这项多中心研究旨在探讨德国一项扩展获取计划(EAP)中托弗森治疗期间的临床和患者报告结局(PRO)以及血清神经丝轻链(sNfL)。

方法：分析了16例接受托弗森治疗至少6个月的SOD1-ALS患者。研究了ALS进展率（ALS-PR），以ALS功能评定量表修订版（ALSFRS-R）、慢肺活量（SVC）和sNfL的月变化量来衡量。PRO包括自我测量医疗结果量表（MYMOP2）、药物治疗满意度问卷（TSQM-9）和净推荐值（NPS）。

结果：托弗森平均治疗时间为11个月（6-18个月）。ALS-PR平均变化量为-0.2（范围0至-1.1），相对降低25%。7例患者ALSFRS-R升高。SVC保持稳定（平均88%，范围-15%至+28%）。除1例杂合D91A-SOD1突变携带者外，所有患者的sNfL均降低（sNfL平均变化量为-58%，范围-91%至+27%，p < .01）。 MYMOP2 表明症状严重程度有所改善（n = 10）或仍有部分缓解（n = 6）。TSQM-9 显示总体治疗满意度较高（平均值 83，标准差 16），尽管给药便利性一般（平均值 50，标准差 27）。NPS 显示托弗森的推荐率非常高（NPS +80）。

讨论：本 EAP 数据支持 SOD1-ALS 患者对托弗森的临床和 sNfL 反应。PRO 表明患者对托弗森治疗在临床实践中的良好感受。

Muscle Nerve . 2024 Sep;70(3):333-345.

 doi: 10.1002/mus.28182. Epub 2024 Jun 20.

Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS-A multicenter observational study over 18 months

 

bstract

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.

Methods: 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).

Results: 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).

Discussion: 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.