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Background: Circulating immune cells play a pathogenic role in multiple sclerosis (MS). However, the role of specific lymphocyte subpopulations is not unveiled yet, especially in progressive stages. We aimed to investigate lymphocyte changes during siponimod treatment in active secondary progressive MS (aSPMS) and their associations with clinical outcomes.
Methods: We enrolled 46 aSPMS patients starting on siponimod treatment with at least 6 months of follow-up and two visits within the scheduled timeframes and 14 sex- and age-matched healthy controls (HCs). Clinical and laboratory data were collected retrospectively at baseline, 3rd, 6th, 12th, and 24th month for MS patients, and at baseline for HCs.
Results: At baseline SPMS patients presented with increased naïve regulatory T lymphocytes (p = 0.02) vs. HCs. Over time, SPMS patients showed decreased T CD4+ (coeff. range = -24/-17, 95% CI range = -31.60 to -10.40), B lymphocyte (coeff. range = -3.77/-2.54, 95% CI range = -6.02 to -0.35), memory regulatory B cells (coeff. range = -0.78/-0.57, 95% CI range = -1.24 to -0.17) and CD4/CD8 ratio (coeff. range = -4.44/-0.67, 95% CI range = -1.61 to -0.17) from month 3 thereafter vs. baseline, and reduced CD3+CD20+ lymphocytes from month 12 thereafter (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03). Patients not experiencing disability progression while on siponimod treatment showed B lymphocyte reduction from month 3 (coeff. range = -4.23/-2.32, 95% CI range = -7.53 to -0.15) and CD3+CD20+ lymphocyte reduction from month 12 (coeff. range = -0.32/-0.24, 95% CI range = -0.59 to -0.03) vs. patients experiencing progression.
Conclusions: Patients treated with siponimod showed a T and B lymphocyte reduction, especially CD4+, CD3+CD20+ and naïve regulatory T cells and memory regulatory B cells. Disability progression while on siponimod treatment was associated with a less pronounced effect on B and CD3+CD20+ lymphocytes.
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http://dx.doi.org/10.1007/s00415-024-12362-9 | DOI Listing |
FASEB J
August 2025
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
This study investigates the repurposing of BAF312 (Siponimod), an FDA-approved sphingosine-1-phosphate (S1P) receptor agonist for multiple sclerosis, as a dual-targeting therapeutic agent for glioma by inhibiting tumor growth and normalizing aberrant tumor vasculature. The clinical correlations between S1PR1/5 expression and glioma prognosis were analyzed using the GEPIA and HPA databases. The effects of BAF312 on tumor growth, cell cycle progression, apoptosis, and vascular remodeling were evaluated using orthotopic GL261 glioma models and glioma cell lines (U118MG, T98G, GL261).
View Article and Find Full Text PDFJ Neurol
August 2025
Second Division of Neurology, Department of Advanced Medical and Surgical Sciences, University of Campania Vanvitelli, Naples, Italy.
Introduction: Sphingosine-1-phosphate (S1P) receptor modulators, regulating the S1P/S1PR pathway, lead to lymphocyte sequestration in lymphoid organs, which results in peripheral lymphopenia. This study evaluates the degree of lymphopenia induced by S1P modulators in people with Multiple Sclerosis (MS): Ozanimod, Siponimod, Ponesimod, and Fingolimod.
Methods: We conducted a retrospective multicenter study across thirteen MS centers in Italy, including 191 MS patients (mean age 46.
Eur J Neurol
July 2025
Department of Neurology, Medical University of Vienna, Vienna, Austria.
Objectives: This study aims to assess the efficacy of de-escalating from natalizumab (NTZ) to cladribine (CLAD), dimethyl fumarate (DMF), fingolimod (FTY), ponesimod (PONE), siponimod (SIPO) and teriflunomide (TERI).
Material And Methods: We analyzed data from 388 patients in the Austrian MS Treatment Registry who initiated NTZ treatment and remained on therapy for at least 3 months before switching to one of the moderately effective therapies within 1 year. Patients were required to remain on the de-escalation therapy for at least 3 months.
Neurol Ther
August 2025
Biogen, 225 Binney St, Cambridge, MA, 02143, USA.
Introduction: Multiple sclerosis (MS) is a heterogeneous disease that disproportionately impacts Black people with MS (PwMS), who experience more severe disease and higher relapse rates compared with non-Black populations. Despite widespread use of fumarates and sphingosine-1-phosphate (S1P) receptor modulators as oral disease-modifying therapies (DMTs) for relapsing MS, their comparative effectiveness in Black PwMS has not been studied. This study aims to help address this gap using real-world claims data.
View Article and Find Full Text PDFBrain Behav
June 2025
Department of Health Sciences (DISSAL), University of Genova, Genova, Italy.
Background: Evidence from clinical trials providing average effects in populations is often used to forecast individualized patient outcomes similar to the trial patients. Multiple sclerosis (MS), known for notable heterogeneity in outcomes, makes the evaluation of potential heterogeneity of treatment effect (HTE) significant. Identifying factors that predict individual treatment response is crucial for optimizing patient care, and this study aimed to demonstrate the feasibility (proof of concept) of applying a statistical method to predict individual treatment response in MS trials.
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