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Blood neurofilament light levels segregate treatment effects in multiple sclerosis

Artikel i vetenskaplig tidskrift
Författare Bénédicte Delcoigne
Ali Manouchehrinia
Christian Barro
Pascal Benkert
Zuzanna Michalak
Ludwig Kappos
David Leppert
Jon A. Tsai
Tatiana Plavina
Bernd C. Kieseier
Jan Lycke
Lars Alfredsson
Ingrid Kockum
Jens Kuhle
Tomas Olsson
Fredrik Piehl
Publicerad i Neurology
Volym 94
Sidor e1201-e1212
Publiceringsår 2020
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap
Sidor e1201-e1212
Språk en
Länkar doi.org/10.1212/WNL.000000000000909...
Ämneskategorier Neurologi, Neurovetenskaper

Sammanfattning

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. OBJECTIVE: To determine factors (including the role of specific disease modulatory treatments [DMTs]) associated with (1) baseline, (2) on-treatment, and (3) change (from treatment start to on-treatment assessment) in plasma neurofilament light chain (pNfL) concentrations in relapsing-remitting multiple sclerosis (RRMS). METHODS: Data including blood samples analyses and long-term clinical follow-up information for 1,261 Swedish patients with RRMS starting novel DMTs were analyzed using linear regressions to model pNfL and changes in pNfL concentrations as a function of clinical variables and DMTs (alemtuzumab, dimethyl fumarate, fingolimod, natalizumab, rituximab, and teriflunomide). RESULTS: The baseline pNfL concentration was positively associated with relapse rate, Expanded Disability Status Scale score, Age-Related MS Severity Score, and MS Impact Score (MSIS-29), and negatively associated with Symbol Digit Modalities Test performance and the number of previously used DMTs. All analyses, which used inverse propensity score weighting to correct for differences in baseline factors at DMT start, highlighted that both the reduction in pNfL concentration from baseline to on-treatment measurement and the on-treatment pNfL level differed across DMTs. Patients starting alemtuzumab displayed the highest reduction in pNfL concentration and lowest on-treatment pNfL concentrations, while those starting teriflunomide had the smallest decrease and highest on-treatment levels, but also starting from lower values. Both on-treatment pNfL and decrease in pNfL concentrations were highly dependent on baseline concentrations. CONCLUSION: Choice of DMT in RRMS is significantly associated with degree of reduction in pNfL, which supports a role for pNfL as a drug response marker.

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