Evidence map›Paper›PMID 41990287›Full record

Trial reportNeurology(R) neuroimmunology & neuroinflammation2026

Dynamics of Spinal Fluid Immune Cell Alterations Following Cladribine Tablet Treatment in Multiple Sclerosis.

Roman A Smirnov, Claudia Cantoni, Kenneth Lee, Rea A Agnihotri, Robert C Axtell, Amber Salter, Samantha Lancia, Michael A Paley, Brooke Hayward, Julie Korich and 9 more

Abstract readRandomized Controlled TrialClinical Trial, Phase IV
In one paragraph

Trial report in Neurology(R) neuroimmunology & neuroinflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Roman A SmirnovDepartment of Medicine, Washington University in St. Louis.ORCID 0009-0006-8793-6144
Claudia CantoniDepartment of Translational Neuroscience, Barrow Neurological Institute, Phoenix, AZ.ORCID 0000-0003-1868-4511
Kenneth LeeDepartment of Neurology, Washington University in St. Louis.
Rea A AgnihotriDepartment of Neurology, Washington University in St. Louis.
Robert C AxtellDepartment of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Multiple Sclerosis Center of Excellence, Oklahoma Medical Research Foundation.ORCID 0000-0001-6041-4588
Amber SalterDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-1088-110X
Samantha LanciaDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0001-8871-7134
Michael A PaleyDepartment of Medicine, Washington University in St. Louis.ORCID 0000-0001-8724-3176
Brooke HaywardEMD Serono, Boston, MA.ORCID 0000-0002-1234-7445
Julie KorichEMD Serono, Boston, MA.
Emily EvansEMD Serono, Boston, MA.
Gabriel PardoDepartment of Arthritis and Clinical Immunology Research, Oklahoma Medical Research Foundation, Multiple Sclerosis Center of Excellence, Oklahoma Medical Research Foundation.ORCID 0000-0002-2207-3708
Ahmed Z ObeidatDepartment of Neurology, Medical College of Wisconsin, Milwaukee.ORCID 0000-0002-3549-3277
Olaf StuveDepartment of Neurology, University of Texas Southwestern Medical Center, Dallas.ORCID 0000-0002-0469-6872
Amit Bar-OrThe Center for Neuroinflammation and Experimental Therapeutics and the Department of Neurology, University of Pennsylvania, Philadelphia; and.ORCID 0000-0001-7179-0335
Maxim N ArtyomovDepartment of Pathology and Immunology, Washington University in St. Louis.ORCID 0000-0002-1133-4212
Anne H CrossDepartment of Neurology, Washington University in St. Louis.ORCID 0000-0003-0829-7569
Brian T EdelsonDepartment of Pathology and Immunology, Washington University in St. Louis.ORCID 0000-0003-2856-7650
Gregory F WuDepartment of Neurology, Washington University in St. Louis.ORCID 0000-0003-3588-0637

Funding

Washington University Rheumatic DiseasesResearch Resource-based CenterP30AR073752 · NIAMS · WASHINGTON UNIVERSITY · PI Christine T. Pham · 2018 to 2026
$7.6M
NIAMS NIH HHS P30 AR073752
6 · The paper itself

Abstract

BACKGROUND AND

objectivesOral cladribine tablet (CladT) therapy is efficacious for relapsing multiple sclerosis (MS). However, the mechanisms by which cladribine exerts benefit in MS remain unclear, particularly regarding its effects on compartmentalized inflammation within the CSF.

methodsTranscriptional profiles along with T and B lymphocyte receptor repertoires from CSF and blood were obtained by single-cell sequencing methods from a single site participating in a phase IV clinical trial investigating the impact of cladribine treatment for MS. Blood and CSF samples from patients were obtained immediately before starting CladT therapy, and they were randomized to also provide additional samples at either 5 weeks, 10 weeks, 1 year, or 2 years after CladT therapy. Thirty-four samples from 13 individuals with relapsing MS before and after treatment were available to test the hypothesis that CladT alters the composition and phenotype of lymphocytes in the CSF, including paired baseline and post-CladT CSF samples obtained from 4 unique participants.

resultsWe found that treatment with CladT profoundly altered cellular composition, but not the transcriptional phenotype, of immune cells in the CSF. In particular, we identified a reduction in switched memory B cells but recovery of naive B cells in the CSF, similar to our findings in blood. In addition, populations of CD4 Treg cells emerged early after CladT therapy and remained elevated 1 year later in the CSF, but not in the blood. Antigen receptor sequencing revealed a moderate decrease in numbers of large clonally expanded CD8 T cell clones (>10 cells/clone) primarily in the CSF, but also in the blood after CladT treatment. DISCUSSION: Our results identified unique cellular dynamics and changes in T cell and B cell clonality in both tissues, which can potentially explain long-term beneficial effects of CladT therapy in MS, including preservation of immune function and a relatively low number of side effects. Altogether, this study demonstrates that CladT treatment had a substantial impact not only on blood but also on the CSF compartment, highlighting the importance of cross-tissue analysis for better understanding of effect and the mechanism of action of disease-modifying therapies.

Indexed as

CladribineImmunosuppressive AgentsMultiple Sclerosis, Relapsing-RemittingAdultFemaleHumansMaleMiddle AgedTabletsCladribineImmunosuppressive AgentsTablets

Identifiers

PMID41990287
PMCPMC13088194

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.