Dimethyl fumarate reduces the frequency and function of inflammatory immune cells in relapsing-remitting multiple sclerosis patients

Author(s):  
Gwendoline Montes Diaz
2018 ◽  
Vol 25 (6) ◽  
pp. 876-879 ◽  
Author(s):  
James Triplett ◽  
Srimathy Vijayan ◽  
Richard Prince ◽  
Allan Kermode

Background: Dimethyl fumarate (DMF) is a commonly used and effective treatment for relapsing and remitting multiple sclerosis. Its use results in impairment of the transcription factor nuclear factor erythroid-derived 2 (E2)-related factor (Nrf2), which is involved in both immunomodulation and bone health. DMF has not previously been reported to cause bone marrow complications, though other fumarates including tenofovir have. The mechanism of fumarate-associated bone toxicity remains unclear with altered osteoblastic gene expression and function suggested. Methods: We present a case of a 54-year-old female with relapsing remitting multiple sclerosis (RRMS) treated for 30 months with DMF who developed relapsing atraumatic lower limb bone pain. Results: Serial imaging revealed multifocal areas of bone marrow oedema and trabecular fractures. The patient was diagnosed with transient bone marrow oedema syndrome. Management consisted of cessation of therapy and treatment with the pro-osteobalstic agent denosumab. Conclusion: In this instance of DMF-associated bone marrow oedema, cessation of DMF and treatment with denosumab resulted in symptomatic improvement. DMF therapy may potentially result in bone marrow oedema due to inhibition of common upstream signalling pathways, including the Nrf2 signalling pathway.


2017 ◽  
Vol 3 (2) ◽  
pp. 205521731770293 ◽  
Author(s):  
C Chaves ◽  
R Ganguly ◽  
C Ceresia ◽  
A Camac

Background Recent data suggest that lymphopenia is more prevalent than reported in relapsing–remitting multiple sclerosis (RRMS) patients taking dimethyl fumarate (DMF). Objective The objective of this study was to investigate the effect of DMF on lymphocyte subtypes in RRMS patients with and without lymphopenia. Method A retrospective study compared lymphocyte subtypes in DMF-treated RRMS patients with low (G1, n = 35) and normal lymphocyte counts (G2, n = 24). Results Fifty-nine patients were identified, with mean age 49, 71.2% females, and average DMF duration 20 months. Age, sex, baseline white blood count, disease and treatment durations were similar between groups. Prior interferon therapy and baseline lower normal lymphocyte counts were more frequent in G1. Mean lymphocyte counts were 0.8 ± 0.2 × 109/L in G1 and 1.6 ± 0.3 × 109/L in G2. CD3+, CD4+, and CD8+ T cell mean counts were lower ( p < 0.0001), while CD4/CD8 ratio higher ( p = 0.03) in G1 than G2. Mean CD19 + B cell counts were normal; however, values were lower in G1 ( p = 0.04). After adjusting for confounders, significantly positive correlations were noted between lymphocyte counts and CD3 + , CD4+, CD8+ T, and B cell counts. Negative correlation was observed between lymphocyte counts and CD4/CD8 ratio driven by low CD8+ T cell counts. Conclusion DMF treatment predominantly impacts T cells, in particular CD8+ subtype. This finding may have implications in this population’s immunocompetence.


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