Increasing Neurofilament and Glial Fibrillary Acidic Protein After Treatment Discontinuation Predicts Multiple Sclerosis Disease Activity.

Humans Female Middle Aged Male Multiple Sclerosis / diagnostic imaging Intermediate Filaments / metabolism Glial Fibrillary Acidic Protein / metabolism Biomarkers Magnetic Resonance Imaging

Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
11 2023
Historique:
received: 20 06 2023
accepted: 17 08 2023
medline: 16 10 2023
pubmed: 14 10 2023
entrez: 9 10 2023
Statut: epublish

Résumé

Stable patients with multiple sclerosis (MS) may discontinue treatment, but the risk of disease activity is unknown. Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are biomarkers of subclinical disease activity and may help risk stratification. In this study, sNfL and sGFAP levels in stable patients were evaluated before and after treatment discontinuation to determine association with disease activity. This observational study included patients enrolled in the Comprehensive Longitudinal Investigation in MS at the Brigham and Women's Hospital who discontinued treatment after >2 years disease activity-free. Two serum samples within 2 years, before and after treatment stop, were sent for sNfL and sGFAP measurements by single-molecule array. Biannual neurologic examinations and yearly MRI scans determined disease activity by 3 time-to-event outcomes: 6-month confirmed disability worsening (CDW), clinical attacks, and MRI activity (new T2 or contrast-enhancing lesions). Associations between each outcome and log-transformed sNfL and sGFAP levels pretreatment stop and posttreatment stop and the percent change were estimated using multivariable Cox regression analysis adjusting for age, disability, disease duration, and duration from attack before treatment stop. Seventy-eight patients (92% female) discontinued treatment at a median (interquartile range) age of 48.5 years (39.0-55.7) and disease duration of 12.3 years (7.5-18.8) and were followed up for 6.3 years (4.2-8.5). CDW occurred in 27 patients (35%), new attacks in 19 (24%), and new MRI activity in 26 (33%). Higher posttreatment stop sNfL level was associated with CDW (adjusted hazard ratio (aHR) 2.80, 95% CI 1.36-5.76, Stable patients who discontinue treatment may be risk stratified by sNfL and sGFAP levels measured before and after discontinuing treatment. Further studies are needed to validate findings and determine whether resuming treatment in patients with increasing biomarker levels reduces risk of subsequent disease activity.

Sections du résumé

BACKGROUND AND OBJECTIVES
Stable patients with multiple sclerosis (MS) may discontinue treatment, but the risk of disease activity is unknown. Serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) are biomarkers of subclinical disease activity and may help risk stratification. In this study, sNfL and sGFAP levels in stable patients were evaluated before and after treatment discontinuation to determine association with disease activity.
METHODS
This observational study included patients enrolled in the Comprehensive Longitudinal Investigation in MS at the Brigham and Women's Hospital who discontinued treatment after >2 years disease activity-free. Two serum samples within 2 years, before and after treatment stop, were sent for sNfL and sGFAP measurements by single-molecule array. Biannual neurologic examinations and yearly MRI scans determined disease activity by 3 time-to-event outcomes: 6-month confirmed disability worsening (CDW), clinical attacks, and MRI activity (new T2 or contrast-enhancing lesions). Associations between each outcome and log-transformed sNfL and sGFAP levels pretreatment stop and posttreatment stop and the percent change were estimated using multivariable Cox regression analysis adjusting for age, disability, disease duration, and duration from attack before treatment stop.
RESULTS
Seventy-eight patients (92% female) discontinued treatment at a median (interquartile range) age of 48.5 years (39.0-55.7) and disease duration of 12.3 years (7.5-18.8) and were followed up for 6.3 years (4.2-8.5). CDW occurred in 27 patients (35%), new attacks in 19 (24%), and new MRI activity in 26 (33%). Higher posttreatment stop sNfL level was associated with CDW (adjusted hazard ratio (aHR) 2.80, 95% CI 1.36-5.76,
DISCUSSION
Stable patients who discontinue treatment may be risk stratified by sNfL and sGFAP levels measured before and after discontinuing treatment. Further studies are needed to validate findings and determine whether resuming treatment in patients with increasing biomarker levels reduces risk of subsequent disease activity.

Identifiants

DOI: 10.1212/NXI.0000000000200167 PMID: 37813595 PMC: PMC10574823
pubmed: 37813595
pii: 10/6/e200167
doi: 10.1212/NXI.0000000000200167
pmc: PMC10574823
pii:
doi:

Substances chimiques

Glial Fibrillary Acidic Protein 0
Biomarkers 0

Types de publication

Observational Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Références

Mult Scler Relat Disord. 2023 Jun;74:104695
pubmed: 37060852
Mult Scler Relat Disord. 2022 Mar;59:103535
pubmed: 35078125
Sci Rep. 2020 Jul 2;10(1):10923
pubmed: 32616916
Neurol Neuroimmunol Neuroinflamm. 2019 Aug 08;6(5):e598
pubmed: 31516913
J Neurol. 2021 Apr;268(4):1247-1253
pubmed: 32929591
Mult Scler. 2022 Oct;28(11):1685-1696
pubmed: 36059263
Mult Scler Relat Disord. 2019 Oct;35:119-127
pubmed: 31374460
Stat Med. 2012 Oct 15;31(23):2676-86
pubmed: 22307964
J Neurol. 2020 Dec;267(12):3518-3527
pubmed: 32617659
J Neuroimaging. 2018 Jan;28(1):36-47
pubmed: 29235194
Mult Scler. 2021 Aug;27(9):1391-1402
pubmed: 33104449
Transl Psychiatry. 2021 Aug 21;11(1):436
pubmed: 34420032
J Magn Reson Imaging. 2002 Feb;15(2):203-9
pubmed: 11836778
Can J Neurol Sci. 2020 Jul;47(4):437-455
pubmed: 32654681
Ann Clin Transl Neurol. 2018 Oct 16;5(12):1478-1491
pubmed: 30564615
Lancet Neurol. 2022 Mar;21(3):246-257
pubmed: 35182510
Ann Clin Transl Neurol. 2020 Jun;7(6):945-955
pubmed: 32452160
Front Neurol. 2021 Mar 17;12:647811
pubmed: 33815259
Mult Scler Relat Disord. 2021 Jan;47:102591
pubmed: 33142245
Neurology. 2020 Mar 17;94(11):e1201-e1212
pubmed: 32047070
Neurol Neuroimmunol Neuroinflamm. 2021 Aug 4;8(5):
pubmed: 34348969
Lancet Neurol. 2018 Feb;17(2):162-173
pubmed: 29275977
Stat Med. 2011 May 10;30(10):1105-17
pubmed: 21484848
Neurol Neuroimmunol Neuroinflamm. 2022 Nov 14;10(1):
pubmed: 36376097
Lancet Neurol. 2023 Jul;22(7):568-577
pubmed: 37353277
Am J Manag Care. 2016 Jun;22(6 Suppl):s151-8
pubmed: 27356024
Mult Scler Relat Disord. 2021 Sep;54:103090
pubmed: 34182224
JAMA Neurol. 2019 Nov 01;76(11):1359-1366
pubmed: 31403661
Sci Rep. 2018 Oct 4;8(1):14798
pubmed: 30287870
J Biomed Inform. 2020 Aug;108:103496
pubmed: 32652236
Neurology. 2017 Feb 28;88(9):826-831
pubmed: 28148632
J Neurol Sci. 2018 Aug 15;391:72-76
pubmed: 30103975
Mult Scler. 2017 Apr;23(4):597-603
pubmed: 27364325
Neurology. 2017 Nov 28;89(22):2230-2237
pubmed: 29079686
Neurol Neuroimmunol Neuroinflamm. 2021 Feb 8;8(2):
pubmed: 33558306
Autoimmun Rev. 2006 Oct;5(8):532-6
pubmed: 17027888
J Lab Autom. 2016 Aug;21(4):533-47
pubmed: 26077162
Mult Scler. 2020 Apr;26(5):540-547
pubmed: 31965903
Mult Scler. 2017 Aug;23(9):1241-1248
pubmed: 27765877
Ann Neurol. 2017 Jun;81(6):857-870
pubmed: 28512753
Mult Scler. 2022 Sep;28(10):1491-1497
pubmed: 33565908
Mult Scler. 2019 Apr;25(5):699-708
pubmed: 29557704
Mult Scler Relat Disord. 2021 May;50:102810
pubmed: 33556656

Auteurs

Gauruv Bose (G)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.
ORCID: 0000-0002-5204-6348

Brian C Healy (BC)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.

Shrishti Saxena (S)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.

Fermisk Saleh (F)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.

Bonnie I Glanz (BI)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.

Rohit Bakshi (R)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.
ORCID: 0000-0001-8601-5534

Howard L Weiner (HL)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada.

Tanuja Chitnis (T)

From the Department of Neurology (G.B., B.C.H., S.S., F.S., B.I.G., R.B., H.L.W., T.C.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School (G.B., B.C.H., B.I.G., R.B., H.L.W., T.C.), Boston, MA; The University of Ottawa and Ottawa Hospital Research Institute (G.B.), Ottawa, Canada. tchitnis@rics.bwh.harvard.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Maladies auto-immunes du système nerveux › Maladies démyélinisantes auto-immunes du SNC › Sclérose en plaques › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Cytosquelette › Filaments intermédiaires › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines du cytosquelette › Protéines de filaments intermédiaires › Protéine gliofibrillaire acide › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Increasing Neurofilament and Glial Fibrillary...
questionsmedicales.fr › Diagnostic › Techniques et procédures diagnostiques › Imagerie diagnostique › Tomographie › Imagerie par résonance magnétique › Increasing Neurofilament and Glial Fibrillary...