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Delayed and recurrent dimethyl fumarate induced-lymphopenia in patients with multiple sclerosis
S Borrelli1, A Mathias1, G Le Goff1
1Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Rue du Bugnon 46, Lausanne 1011, Switzerland.
Background:
Early lymphopenia is a known side effect of dimethyl fumarate, a disease-modifying therapy for MS. However, the long-term effects on immune response and the impact on lymphocyte counts when another disease-modifying treatment is introduced, remain unknown. To better understand these specific aspects, we reviewed cases that develop prolonged grade 2 to 4 lymphopenia under dimethyl fumarate in Lausanne MS clinic.
Method:
Retrospective analysis of the 12 patients (10.1%) who discontinued dimethyl fumarate because of prolonged lymphopenia amongst the 119 patients treated with dimethyl fumarate. We reviewed their demographics, as well as their clinical, biological and MRI characteristics compared to the non-lymphopenic patients, during dimethyl fumarate therapy, and within a timeframe of up to 18 months after switching to another disease-modifying treatment. We also focused on lymphocyte subsets in a subgroup of patients.
Results:
Compared to non-lymphopenic patients, lymphopenic patients were older at dimethyl fumarate initiation (51.4 yo vs 39.7, p = 0.0003) and the majority were male (p = 0.037). Three of them (25%) developed delayed lymphopenia, more than one year after treatment onset. Despite persistent lymphopenia, three patients experienced disease activity. Amongst the nine patients (75%) who were switched to another therapy, five (55.6%) presented recurrent lymphopenia, predominantly with a CD8+ T cell decrease.
Conclusions:
Dimethyl fumarate has a long-term impact on lymphocyte biology, even after its discontinuation, with a sustained reduction in CD8+ T cells that may increase opportunistic infection risk, and should be taken in consideration when switching therapies after dimethyl fumarate.
Insights
Dimethyl fumarate can cause long-term lymphopenia, affecting CD8+ T cells even after stopping the drug. This sustained immune impact requires consideration when switching multiple sclerosis therapies.
Area of Science:
- Immunology
- Neurology
- Pharmacology
Background:
- Dimethyl fumarate (DMF) is a disease-modifying therapy for multiple sclerosis (MS).
- Early lymphopenia is a known side effect of DMF.
- Long-term immune effects and lymphocyte count changes after switching DMF are not well understood.
Purpose of the Study:
- To investigate the long-term effects of dimethyl fumarate on lymphocyte counts.
- To analyze immune response changes after switching DMF therapy.
- To understand the impact of prolonged lymphopenia in MS patients.
Main Methods:
- Retrospective analysis of 12 patients with prolonged grade 2-4 lymphopenia on DMF.
- Comparison of demographics, clinical, biological, and MRI data with non-lymphopenic patients.
- Analysis of lymphocyte subsets in a subgroup of patients up to 18 months post-DMF.
Main Results:
- Lymphopenic patients were older and predominantly male at DMF initiation.
- Delayed lymphopenia occurred in 25% of patients over a year after starting DMF.
- Recurrent lymphopenia was observed in 55.6% of patients switched to other therapies, mainly due to CD8+ T cell reduction.
Conclusions:
- Dimethyl fumarate has lasting effects on lymphocyte biology, including sustained CD8+ T cell reduction.
- This long-term impact on immune cells persists even after DMF discontinuation.
- Consideration of sustained lymphopenia is crucial when switching MS therapies post-DMF.
