ethyl-fumarate and Multiple-Sclerosis

To test the hypothesis that dimethyl fumarate (DMF, Tecfidera) elicits different biological changes from DMF combined with monoethyl fumarate (MEF) (Fumaderm, a psoriasis therapy), we investigated DMF and MEF in rodents and cynomolgus monkeys. Possible translatability of findings was explored with lymphocyte counts from a retrospective cohort of patients with MS.. In rodents, we evaluated pharmacokinetic and pharmacodynamic effects induced by DMF and MEF monotherapies or in combination (DMF/MEF). Clinical implications were investigated in a retrospective, observational analysis of patients with MS treated with DMF/MEF (n = 36).. Fumaric acid esters exhibit different biodistribution and may elicit different biological responses; furthermore, pharmacodynamic effects of combinations differ unpredictably from monotherapy. The strong potential to induce lymphopenia in patients with MS may be a result of activation of apoptosis pathways by MEF compared with DMF.

Topics: Animals; Cross-Sectional Studies; Dimethyl Fumarate; Female; Fumarates; Gene Expression Profiling; Humans; Immunosuppressive Agents; Macaca fascicularis; Male; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Rats; Rats, Sprague-Dawley; Retrospective Studies