Detecting ongoing disease activity in mildly affected multiple sclerosis patients under first-line therapies.

Biomarker Disease activity measurements Early MS NEDA Neurofilament light chain PIRA RAW Relapsing-remitting multiple sclerosis

Journal

Multiple sclerosis and related disorders
ISSN: 2211-0356
Titre abrégé: Mult Scler Relat Disord
Pays: Netherlands
ID NLM: 101580247

Informations de publication

Date de publication:
Jul 2022
Historique:
received: 18 04 2022
revised: 19 05 2022
accepted: 27 05 2022
pubmed: 15 6 2022
medline: 29 6 2022
entrez: 14 6 2022
Statut: ppublish

Résumé

The current range of disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has placed more importance on the accurate monitoring of disease progression for timely and appropriate treatment decisions. With a rising number of measurements for disease progression, it is currently unclear how well these measurements or combinations of them can monitor more mildly affected RRMS patients. To investigate several composite measures for monitoring disease activity and their potential relation to the biomarker neurofilament light chain (NfL) in a clearly defined early RRMS patient cohort with a milder disease course. From a total of 301 RRMS patients, a subset of 46 patients being treated with a continuous first-line therapy was analyzed for loss of no evidence of disease activity (lo-NEDA-3) status, relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA), up to seven years after treatment initialization. Kaplan-Meier estimates were used for time-to-event analysis. Additionally, a Cox regression model was used to analyze the effect of NfL levels on outcome measures in this cohort. In this mildly affected cohort, both lo-NEDA-3 and PIRA frequently occurred over a median observational period of 67.2 months and were observed in 39 (84.8%) and 23 (50.0%) patients, respectively. Additionally, 12 out of 26 PIRA manifestations (46.2%) were observed without a corresponding lo-NEDA-3 status. Jointly, either PIRA or lo-NEDA-3 showed disease activity in all patients followed-up for at least the median duration (67.2 months). NfL values demonstrated an association with the occurrence of relapses and RAW. The complementary use of different disease progression measures helps mirror ongoing disease activity in mildly affected early RRMS patients being treated with continuous first-line therapy.

Sections du résumé

BACKGROUND BACKGROUND
The current range of disease-modifying treatments (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has placed more importance on the accurate monitoring of disease progression for timely and appropriate treatment decisions. With a rising number of measurements for disease progression, it is currently unclear how well these measurements or combinations of them can monitor more mildly affected RRMS patients.
OBJECTIVES OBJECTIVE
To investigate several composite measures for monitoring disease activity and their potential relation to the biomarker neurofilament light chain (NfL) in a clearly defined early RRMS patient cohort with a milder disease course.
METHODS METHODS
From a total of 301 RRMS patients, a subset of 46 patients being treated with a continuous first-line therapy was analyzed for loss of no evidence of disease activity (lo-NEDA-3) status, relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA), up to seven years after treatment initialization. Kaplan-Meier estimates were used for time-to-event analysis. Additionally, a Cox regression model was used to analyze the effect of NfL levels on outcome measures in this cohort.
RESULTS RESULTS
In this mildly affected cohort, both lo-NEDA-3 and PIRA frequently occurred over a median observational period of 67.2 months and were observed in 39 (84.8%) and 23 (50.0%) patients, respectively. Additionally, 12 out of 26 PIRA manifestations (46.2%) were observed without a corresponding lo-NEDA-3 status. Jointly, either PIRA or lo-NEDA-3 showed disease activity in all patients followed-up for at least the median duration (67.2 months). NfL values demonstrated an association with the occurrence of relapses and RAW.
CONCLUSION CONCLUSIONS
The complementary use of different disease progression measures helps mirror ongoing disease activity in mildly affected early RRMS patients being treated with continuous first-line therapy.

Identifiants

pubmed: 35700670
pii: S2211-0348(22)00438-2
doi: 10.1016/j.msard.2022.103927
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103927

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.

Auteurs

Lars Masanneck (L)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany; Hasso Plattner Institute, University of Potsdam, 14482 Potsdam, Germany.

Leoni Rolfes (L)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Liesa Regner-Nelke (L)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Alice Willison (A)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Saskia Räuber (S)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Falk Steffen (F)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Stefan Bittner (S)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Frauke Zipp (F)

Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Philipp Albrecht (P)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Tobias Ruck (T)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Hans-Peter Hartung (HP)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Sven G Meuth (SG)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany.

Marc Pawlitzki (M)

Department of Neurology, Medical Faculty University Hospital Düsseldorf, Düsseldorf, Germany. Electronic address: marcguenter.pawlitzki@med.uni-duesseldorf.de.

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Classifications MeSH