[Dimethyl Fumarate in Multiple Sclerosis].

At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression. The APEX study, which included Japanese patients with RRMS, also showed similar results, but reported some adverse effects. Flushing and gastrointestinal events (e.g., nausea, vomiting, abdominal pain, and diarrhea) occurring within 1 month of the initiation of DMF treatment are major causes of discontinuation of the drug. The most serious adverse event is progressive multifocal leukoencephalopathy (PML), which was reported in four patients with MS treated with DMF, worldwide. Grade 3 lymphopenia (less than 500/mm³) due to apoptosis occurs in some DMF-treated patients with MS and is more prevalent among older patients. A reduction in CD8⁺ T cells is more pronounced than that in CD4⁺ T cells. Patients with grade 3 lymphopenia, aged more than 50 years, are at a risk for PML development. Further studies are needed to determine the appropriate final dose and an acceptable dose-escalation method for DMF treatment, to prevent or decrease adverse effects in Japanese patients with MS.