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Updated: Mar 7, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Effect of Fingolimod on Brain Volume Loss in Patients with Multiple Sclerosis
Nicola De Stefano1, Diego G Silva2, Michael H Barnett3
1Department of Medicine, Surgery and Neuroscience, University of Siena, via le Bracci 2, 53100, Siena, Italy. destefano@unisi.it.
Abstract:
Brain atrophy occurs at a faster rate in patients with multiple sclerosis (MS) than in healthy individuals. In three randomized, controlled, phase III trials, fingolimod reduced the annual rate of brain volume loss (BVL) in patients with relapsing MS (RMS) by approximately one-third relative to that in individuals receiving placebo or intramuscular interferon beta-1a. Analysis of brain volume changes during study extensions has shown that this reduced rate of BVL is sustained in patients with RMS receiving fingolimod continuously. Subgroup analyses of the core phase III and extension studies have shown that reductions in the rate of BVL are observed irrespective of levels of inflammatory lesion activity seen by magnetic resonance imaging at baseline and on study; levels of disability at baseline; and treatment history. The rate of BVL in these studies was predicted independently by T2 lesion and gadolinium-enhancing lesion burdens at baseline, and correlations observed between BVL and increasing levels of disability strengthened over time. In another phase III trial in patients with primary progressive MS (PPMS), fingolimod did not reduce BVL overall relative to placebo; however, consistent with findings in RMS, there was a treatment effect on BVL in patients with PPMS with gadolinium-enhancing lesion activity at baseline. The association between treatment effects on BVL and future accumulation of disability argues in favor of measuring BVL on a more routine basis and with a more structured approach than is generally the case in clinical practice. Despite several practical obstacles, progress is being made in achieving this goal.
Insights
Fingolimod significantly slowed brain volume loss in relapsing multiple sclerosis (MS) patients, with benefits sustained over time. This effect was consistent across various patient subgroups and disease markers.
Area of Science:
- Neuroscience
- Immunology
- Radiology
Background:
- Multiple sclerosis (MS) is characterized by accelerated brain atrophy compared to healthy individuals.
- Brain volume loss (BVL) is a key indicator of neurodegeneration in MS.
- Understanding factors influencing BVL is crucial for MS management.
Purpose of the Study:
- To evaluate the effect of fingolimod on the rate of brain volume loss (BVL) in patients with relapsing MS (RMS) and primary progressive MS (PPMS).
- To assess the long-term sustainability of fingolimod's effect on BVL.
- To identify predictors of BVL and its relationship with disability progression.
Main Methods:
- Analysis of data from three randomized, controlled, phase III trials and their extensions.
- Comparison of annual BVL rates between fingolimod and placebo/interferon beta-1a groups.
- Subgroup analyses based on baseline MRI lesion activity, disability, and treatment history.
- Correlation analysis between BVL, lesion burden, and disability accumulation.
Main Results:
- Fingolimod reduced the annual BVL rate by approximately one-third in RMS patients compared to placebo or interferon beta-1a.
- This reduction in BVL was sustained with continuous fingolimod treatment in RMS.
- BVL reduction was observed irrespective of baseline inflammatory activity, disability, or treatment history in RMS.
- Baseline T2 lesion and gadolinium-enhancing lesion burdens independently predicted BVL.
- In PPMS, fingolimod did not reduce overall BVL but showed a treatment effect in patients with baseline gadolinium-enhancing lesions.
Conclusions:
- Fingolimod effectively reduces brain volume loss in RMS, with sustained effects.
- Brain volume loss is associated with disability progression, highlighting the importance of monitoring BVL.
- Routine and structured measurement of BVL is recommended for improved clinical practice in MS management.
