2026-04-13T04:55:42Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/113862025-10-31T04:53:56Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Fox, Robert J
author
Cree, Bruce
author
de Seze, Jerome
author
Hartung, Hans-Peter
author
Jeffery, Douglas
author
Gold, Ralf
author
Montalban, Xavier
2024-04-29T10:45:24Z2024-04-29T10:45:24Z2024-05-14
Serum neurofilament light chain; Radiologic disease; Multiple sclerosisCadena ligera de neurofilamentos séricos; Enfermedad radiológica; Esclerosis múltipleCadena lleugera de neurofilaments sèrics; Malaltia radiològica; Esclerosi múltipleBackground and Objectives
Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).
Methods
In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28.
Results
Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2–3 (n = 18), 4–9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion.
Discussion
Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.The study was sponsored and funded by Biogen (Cambridge, MA).
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess
Esclerosi múltiple - Imatgeria per ressonància magnètica
Marcadors bioquímics
Filaments citoplasmàtics
DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
Other subheadings::Other subheadings::Other subheadings::/diagnostic imaging
CHEMICALS AND DRUGS::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Neurofilament Proteins
CHEMICALS AND DRUGS::Biological Factors::Biomarkers
ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple
Otros calificadores::Otros calificadores::Otros calificadores::/diagnóstico por imagen
COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::polímeros::biopolímeros::proteínas de filamentos intermedios::proteínas de neurofilamentos
COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores
Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion