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Observational Study
. 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

Thomas Meyer  1   2 , Peggy Schumann  1   2 , Patrick Weydt  3   4 , Susanne Petri  5 , Jochen H Weishaupt  6 , Ute Weyen  7 , Jan C Koch  8 , René Günther  9   10 , Martin Regensburger  11 , Matthias Boentert  12 , Maximilian Wiesenfarth  13 , Yasemin Koc  1 , Felix Kolzarek  2 , Dagmar Kettemann  1 , Jenny Norden  1 , Sarah Bernsen  1   2 , Zeynep Elmas  13 , Julian Conrad  6 , Ivan Valkadinov  6 , Maximilian Vidovic  9 , Johannes Dorst  13   14 , Albert C Ludolph  13   14 , Jasper Hesebeck-Brinckmann  6 , Susanne Spittel  2 , Christoph Münch  1   2 , André Maier  1 , Péter Körtvélyessy  1
Affiliations
Observational Study

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

Thomas Meyer et al. Muscle Nerve. 2024 Sep.

Abstract

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.

Keywords: amyotrophic lateral sclerosis (ALS); clinical course; neurofilament light chain (NfL); patient‐reported outcomes; tofersen.

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References

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