Risk factors for lymphopenia in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate

2019 ◽  
Vol 267 (1) ◽  
pp. 125-131 ◽  
Author(s):  
Fabian Sierra Morales ◽  
Igor J. Koralnik ◽  
Shiva Gautam ◽  
Soleil Samaan ◽  
Jacob A. Sloane
2014 ◽  
Vol 13 (11) ◽  
pp. 1077-1078
Author(s):  
Martyn J Burke ◽  
Joanna Richardson ◽  
Elisabeth George ◽  
Amanda I Adler

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.


2019 ◽  
Vol 90 (4) ◽  
pp. 458-468 ◽  
Author(s):  
Tomas Kalincik ◽  
Eva Kubala Havrdova ◽  
Dana Horakova ◽  
Guillermo Izquierdo ◽  
Alexandre Prat ◽  
...  

ObjectiveOral immunotherapies have become a standard treatment in relapsing-remitting multiple sclerosis. Direct comparison of their effect on relapse and disability is needed.MethodsWe identified all patients with relapsing-remitting multiple sclerosis treated with teriflunomide, dimethyl fumarate or fingolimod, with minimum 3-month treatment persistence and disability follow-up in the global MSBase cohort study. Patients were matched using propensity scores. Three pairwise analyses compared annualised relapse rates and hazards of disability accumulation, disability improvement and treatment discontinuation (analysed with negative binomial models and weighted conditional survival models, with pairwise censoring).ResultsThe eligible cohorts consisted of 614 (teriflunomide), 782 (dimethyl fumarate) or 2332 (fingolimod) patients, followed over the median of 2.5 years. Annualised relapse rates were lower on fingolimod compared with teriflunomide (0.18 vs 0.24; p=0.05) and dimethyl fumarate (0.20 vs 0.26; p=0.01) and similar on dimethyl fumarate and teriflunomide (0.19 vs 0.22; p=0.55). No differences in disability accumulation (p≥0.59) or improvement (p≥0.14) were found between the therapies. In patients with ≥3-month treatment persistence, subsequent discontinuations were less likely on fingolimod than teriflunomide and dimethyl fumarate (p<0.001). Discontinuation rates on teriflunomide and dimethyl fumarate were similar (p=0.68).ConclusionThe effect of fingolimod on relapse frequency was superior to teriflunomide and dimethyl fumarate. The effect of the three oral therapies on disability outcomes was similar during the initial 2.5 years on treatment. Persistence on fingolimod was superior to the two comparator drugs.


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