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. 2024 Nov;30(13):1683-1688.
doi: 10.1177/13524585241293940. Epub 2024 Nov 4.

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients

Alyssa A Toorop  1 , Mark Hj Wessels  1 , Lynn Boonkamp  2 , Liza My Gelissen  1 , E Hoitsma  3 , Esther Mpe Zeinstra  4 , Luuk C van Rooij  5 , Caspar Ep van Munster  6 , Anke Vennegoor  7 , Jop P Mostert  8 , Beatrijs Ha Wokke  9 , Nynke F Kalkers  10 , Erwin Lj Hoogervorst  11 , Jeroen Jj van Eijk  12 , Christiaan M Roosendaal  13 , Jolijn J Kragt  14 , Marijke Eurelings  15 , Jessie van Genugten  16 , Jessica Nielsen  17 , Lgf Sinnige  18 , Mark E Kloosterziel  19 , Edo Pj Arnoldus  20 , Gert W van Dijk  21 , Willem H Bouvy  22 , Eva Mm Strijbis  1 , Bob W van Oosten  1 , Brigit A de Jong  1 , Bernard Mj Uitdehaag  1 , Theo Rispens  23   24 , Joep Killestein  1 , Zoé LE van Kempen  1 , Charlotte E Teunissen  2
Affiliations

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients

Alyssa A Toorop et al. Mult Scler. 2024 Nov.

Abstract

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

Results: A total of 364 participants were included. In total, 55.5% presented with WoS and 44.5% without WoS during natalizumab treatment. Longitudinal analyses showed no association between sNfL and sGFAP levels and WoS at any timepoint. Biomarker levels at baseline did not predict first-time WoS occurrence.

Conclusion: Acute and chronic neuronal and axonal damage are most likely not the underlying cause of WoS.

Keywords: Multiple sclerosis; biomarkers; natalizumab; treatment response.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: A.A.T. has nothing to disclose. M.H.J.W. has nothing to disclose. L.B. has nothing to disclose. L.M.Y.G. has nothing to disclose. E.H. has accepted (speaker and congress) fees from Merck Serono, Biogen Idec, Roche and Sanofi Genzyme. E.M.P.E.Z. reports advisory boards/consultancy fees for Merck, Novartis, Genzyme and Roche. L.C.v.R. has nothing to disclose. C.E.P.v.M. has nothing to disclose. A.V. has nothing to disclose. J.P.M. has nothing to disclose. B.H.A.W. has nothing to disclose. N.F.K. has nothing to disclose. E.L.J.H. has nothing to disclose. J.J.J.v.E. reports honoraria for advisory boards and/or speakers fee from Merck Serono, Biogen Idec, Sanofi Genzyme, Roche and Novartis. C.M.R. has nothing to disclose. J.J.K. has nothing to disclose. M.E. has nothing to disclose. J.N. has nothing to disclose. J.v.G. has nothing to disclose. L.G.F.S. has nothing to disclose. M.E.K. has nothing to disclose. E.P.J.A. has nothing to disclose. G.W.v.D. has nothing to disclose. W.H.B. has nothing to disclose. E.M.M.S. has nothing to disclose. B.W.v.O. has nothing to disclose. B.A.d.J. has nothing to disclose. B.M.J.U. reports research support and/or consultancy fees from Genzyme, Biogen Idec, Novartis, Teva Pharmaceutical Industries, Merck Serono, Roche and Immunic Therapeutics. T.R. received funding for research from Genmab and consultancy fees from Novartis. J.K. received research grants for multicentre investigator-initiated trials DOT-MS trial, ClinicalTrials.gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds) (ClinicalTrials.gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche Ltd, Biogen, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche Ltd, Biogen, Immunic, Teva, Merck, Novartis and Sanofi/Genzyme (all payments to institution) and adjudication committee of MS clinical trial of Immunic (payments to institution only). Z.L.E.v.K. has nothing to disclose. C.E.T. reports funding from National MS Society (Progressive MS alliance) and Innovative Medicines Initiatives 3TR (Horizon 2020, grant no. 831434); has a research contract with Celgene; serves on editorial boards of Medidact Neurologie/Springer, Neurology: Neuroimmunology & Neuroinflammation and is editor of a Neuromethods book Springer.

Figures

Figure 1.
Figure 1.
sNfL and sGFAP levels over time. (a) and (b) The x-axis displays continuous time points (weeks from baseline). The y-axis displays sNfL levels in pg/mL (a) and sGFAP levels in pg/mL (b). Baseline represents the start of extended interval dosing for each dose. Samples for the current study were retrieved at the start of the study, year 1 and last follow-up. The figures illustrate no significant difference in sNfL and sGFAP levels over time between participants with WoS and without WoS. (c)–(f) The x-axis displays timepoints (baseline, year 1 and year 2). The y-axis displays the absolute difference in sNfL ((c) and (e)) and sGFAP ((d) and (f)) levels compared to baseline. The figures illustrate no significant change in biomarker levels between participants with first-time WoS occurrence during follow-up and those without. WoS: wearing-off symptom; sNfL: serum neurofilament light; sGFAP: serum glial fibrillary acidic protein.
See this image and copyright information in PMC

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