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Dimethyl Fumarate, But Not Rituximab, Reduces Serum GFAP Levels and PIRMA in Relapsing-Remitting MS.

F Shawket1, J Lycke2,3, J Salzer4

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Dimethyl fumarate (DMF) and rituximab (RTX) both reduced serum neurofilament light chain (sNfL) in multiple sclerosis (MS) patients. However, only DMF significantly lowered glial fibrillary acidic protein (sGFAP) and reduced the risk of disability progression.

Keywords:
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Area of Science:

  • Neuroimmunology
  • Biomarker Research
  • Clinical Trials

Background:

  • Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are key biomarkers in multiple sclerosis (MS).
  • sNfL is thought to reflect acute disease activity, while sGFAP is associated with chronic neurodegeneration.
  • Investigating differential effects of disease-modifying therapies on these biomarkers is crucial for understanding treatment mechanisms.

Purpose of the Study:

  • To compare the effects of dimethyl fumarate (DMF) and rituximab (RTX) on serum sNfL and sGFAP levels in patients with relapsing-remitting multiple sclerosis (RRMS).
  • To assess whether these therapies differentially impact acute and chronic disease processes as indicated by biomarker changes.
  • To evaluate the association of biomarker changes with clinical and MRI outcomes.

Main Methods:

  • A 2-year, rater-blinded, randomized controlled trial (RIFUND-MS) comparing DMF and RTX in RRMS patients.
  • Serum samples were collected at baseline and multiple time points (0, 6, 12, 24 months) for sNfL and sGFAP analysis.
  • Linear mixed models and Cox proportional hazards models were used to analyze biomarker data and progression outcomes, respectively.

Main Results:

  • Both DMF and RTX significantly reduced sNfL levels from baseline to 24 months, with no significant difference between treatments.
  • sGFAP levels remained stable with RTX but showed a significant decrease with DMF.
  • DMF treatment was associated with a lower risk of progression independent of relapse and MRI activity (PIRMA) compared to RTX.

Conclusions:

  • Both DMF and RTX effectively suppress acute inflammatory activity in MS, as evidenced by sNfL reduction.
  • DMF demonstrates an advantage over RTX in reducing sGFAP, suggesting a potential benefit in addressing chronic neurodegenerative processes.
  • These findings indicate that DMF may offer additional benefits beyond peripheral immune modulation, potentially targeting astrocyte-related pathology and reducing non-inflammatory disability progression in MS.