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Updated: Jan 29, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Effect of dosage reduction on peripheral blood lymphocyte count in patients with multiple sclerosis receiving
1Department of Neurology, Hokuriku Brain and Neuromuscular Disease Center, National Hospital Organization Iou Hospital, Kanazawa, Japan.
Abstract:
Of the 19 cases of fingolimod-associated progressive multifocal leukoencephalopathy (PML) reported worldwide by the end of 2017, 4 cases were from Japan. This may indicate that fingolimod sensitivity is higher in the Japanese population than in the western population because the fingolimod dosage used for the prevention of multiple sclerosis (MS) is the same in both populations. Therefore, the laboratory data of nine patients with MS receiving fingolimod treatment for more than 2 years were retrospectively collected. Moreover, the effect of drug holiday was compared between five patients who underwent at least 3 months of dosage reduction via drug holiday after receiving fingolimod for more than 2 years and three patients who underwent drug holiday after receiving fingolimod for less than 2 years. The total, CD3(+), CD4(+), C19(+) lymphocyte counts, the CD4(+)/CD8(+) cell ratio, and the serum IgG concentrations were similar between Japanese patients with MS receiving fingolimod for more than 2 years and Western patients from the previous reports. Recovery of lymphocyte counts in the peripheral blood after fingolimod dosage reduction was worse in some MS patients who received long-term fingolimod treatment than in MS patients who received short-term fingolimod treatment. My findings indicate that the currently used fingolimod dosage may be too high for some Japanese MS patients receiving long-term fingolimod treatment.
Insights
Fingolimod treatment for multiple sclerosis (MS) may require dosage adjustments in Japanese patients. Long-term use can impair lymphocyte count recovery, suggesting the current dose might be too high for this population.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Progressive multifocal leukoencephalopathy (PML) cases associated with fingolimod were disproportionately reported in Japan.
- This suggests potential population-specific sensitivities to fingolimod, despite uniform dosing for multiple sclerosis (MS) treatment.
- Understanding these differences is crucial for optimizing MS management and patient safety.
Purpose of the Study:
- To investigate laboratory data of Japanese MS patients undergoing long-term fingolimod treatment.
- To compare the effects of drug holidays on lymphocyte recovery between short-term and long-term fingolimod users.
- To assess if current fingolimod dosage is appropriate for long-term use in Japanese MS patients.
Main Methods:
- Retrospective collection of laboratory data from nine Japanese MS patients treated with fingolimod for over two years.
- Comparison of lymphocyte counts (total, CD3+, CD4+, C19+), CD4+/CD8+ ratio, and serum IgG between long-term ( >2 years) and short-term (<2 years) fingolimod users undergoing drug holidays.
- Analysis of recovery rates of peripheral blood lymphocyte counts post-dosage reduction.
Main Results:
- Laboratory parameters (lymphocyte counts, CD4+/CD8+ ratio, IgG) were comparable between Japanese patients on long-term fingolimod and previously reported Western patients.
- Lymphocyte count recovery in peripheral blood after fingolimod dosage reduction was less effective in patients with long-term treatment compared to short-term treatment.
- This indicates a potential impairment in immune reconstitution with prolonged fingolimod exposure.
Conclusions:
- The standard fingolimod dosage may be excessive for some Japanese MS patients undergoing extended treatment.
- Long-term fingolimod therapy might compromise the immune system's ability to recover lymphocytes, increasing potential risks.
- Further research and potential dosage adjustments are warranted for optimizing fingolimod therapy in the Japanese MS population.
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