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Comparison of CSF biomarkers in multiple sclerosis patients treated with natalizumab and rituximab

Hellgren, Johan LU ; Ahlström, Isabella ; Strandberg, Maria Compagno LU ; Jonsson, Magnus Förnvik LU orcid ; Hansson, Oskar LU orcid ; Janelidze, Shorena LU ; Svenningsson, Anders and Källén, Kristina LU (2025) In Multiple Sclerosis and Related Disorders 99.
Abstract

Background: Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF). Objectives: To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition. Methods: This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF... (More)

Background: Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF). Objectives: To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition. Methods: This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF of 30 RRMS patients on NTZ or RTX for at least 24 months. A longitudinal comparison of biomarkers was performed for IgG Indices. Fatigue and cognition outcomes were explored in relation to CSF biomarkers. Results: GFAP level was significantly higher in the NTZ group compared to RTX (mean difference (CI): 2 716 (155; 5278) ng/L, p=0.047). NfL concentration did not differ between the groups. OCBs and k-FLC index were present and elevated in 97 % and 87 % of participants, respectively. IgG-index was significantly reduced only for NTZ. No significant associations were found between fatigue, cognition and the biomarkers. Conclusion: Our results support that intrathecal inflammatory activity is still ongoing in patients with NTZ and RTX. Cross-sectional GFAP might indicate a lower risk for long-term disability in the RTX group. Our data should be interpreted with caution because of small sample size, making it difficult to control for multiple confounders.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Multiple Sclerosis and Related Disorders
volume
99
article number
106479
publisher
Elsevier
external identifiers
  • scopus:105004298526
  • pmid:40345115
ISSN
2211-0348
DOI
10.1016/j.msard.2025.106479
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025
id
e7bd8249-aa9a-4c6d-b180-5f45557e7786
date added to LUP
2025-05-22 09:32:37
date last changed
2025-11-06 23:51:10
@article{e7bd8249-aa9a-4c6d-b180-5f45557e7786,
  abstract     = {{<p>Background: Patients with relapsing remitting multiple sclerosis (RRMS) treated with the high-efficacy drugs natalizumab (NTZ) or rituximab (RTX) generally show no evidence of disease activity. Currently, there is no head-to-head comparison between NTZ and RTX of neurodegenerative and neuroinflammatory biomarkers in cerebrospinal fluid (CSF). Objectives: To compare CSF biomarkers in a stable RRMS cohort treated with NTZ or RTX. A secondary objective was to explore potential associations between CSF biomarkers, fatigue, and cognition. Methods: This Swedish multicentre cross-sectional study assessed kappa-free light chain (k-FLC) index, oligoclonal bands (OCBs), glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in CSF of 30 RRMS patients on NTZ or RTX for at least 24 months. A longitudinal comparison of biomarkers was performed for IgG Indices. Fatigue and cognition outcomes were explored in relation to CSF biomarkers. Results: GFAP level was significantly higher in the NTZ group compared to RTX (mean difference (CI): 2 716 (155; 5278) ng/L, p=0.047). NfL concentration did not differ between the groups. OCBs and k-FLC index were present and elevated in 97 % and 87 % of participants, respectively. IgG-index was significantly reduced only for NTZ. No significant associations were found between fatigue, cognition and the biomarkers. Conclusion: Our results support that intrathecal inflammatory activity is still ongoing in patients with NTZ and RTX. Cross-sectional GFAP might indicate a lower risk for long-term disability in the RTX group. Our data should be interpreted with caution because of small sample size, making it difficult to control for multiple confounders.</p>}},
  author       = {{Hellgren, Johan and Ahlström, Isabella and Strandberg, Maria Compagno and Jonsson, Magnus Förnvik and Hansson, Oskar and Janelidze, Shorena and Svenningsson, Anders and Källén, Kristina}},
  issn         = {{2211-0348}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Multiple Sclerosis and Related Disorders}},
  title        = {{Comparison of CSF biomarkers in multiple sclerosis patients treated with natalizumab and rituximab}},
  url          = {{http://dx.doi.org/10.1016/j.msard.2025.106479}},
  doi          = {{10.1016/j.msard.2025.106479}},
  volume       = {{99}},
  year         = {{2025}},
}