Japanese guidelines for dimethyl fumarate

Abstract

A multicenter, randomized, double‐blind, placebo‐controlled, efficacy and safety study of BG00012 in participants from the Asia–Pacific region and other countries with relapsing–remitting multiple sclerosis (APEX), including Japan, established the efficacy of dimethyl fumarate (DMF) in preventing relapses and disease progression in patients with multiple sclerosis (MS). Consequently, in December 2016, DMF was approved as the second oral disease‐modifying drug for MS in Japan. However, the new Japanese guidelines for MS and neuromyelitis optica published in 2017 did not include DMF. Later, after the committee discussed a guideline for DMF, a supplement of the new guidelines for MS and neuromyelitis optica, which included DMF, was published in June 2018; this supplement comprised the following four clinical questions: (i) is DMF effective in preventing relapses in patients with MS?; (ii) is DMF effective in preventing disease progression in patients with MS?; (iii) how to use DMF?; and (iv) what adverse events does DMF possibly cause? Furthermore, the supplement comprised answers to the questions and comments. Overall, this supplement is anticipated to contribute toward the treatment of Japanese MS patients with DMF.

Disease‐modifying drugs for multiple sclerosis in Japan: A focus on the 2017 Japanese guidelines and the 2018 supplement

“…Flushing accompanied by itching and burning sensations has an incidence of 22-38% based on previous clinical trials. 3,24 Natalizumab Two global phase III clinical trials; that is, the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) 25 and Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) 26 studies, showed significant efficacy in reducing clinical relapse rates and risk of sustained progression of disability. Moderate-to-severe lymphopenia might increase PML risk, and it is recommended to obtain a complete blood count before the treatment and to monitor the lymphocyte count for, at least, every 3 months during the DMF treatment.…”

“…2,4 Regarding effectiveness and longterm safety, the guidelines recommend initiation of treatment with the first-line approved drugs that are injectable. 3,24 Post-marketing data from Italy showed a better clinical and radiological outcome in treatment-na€ ıve patients (started DMF as first treatment) compared with patients who switched from other DMD to DMF. 3,24 Post-marketing data from Italy showed a better clinical and radiological outcome in treatment-na€ ıve patients (started DMF as first treatment) compared with patients who switched from other DMD to DMF.…”

“…Moderate-to-severe lymphopenia might increase PML risk, and it is recommended to obtain a complete blood count before the treatment and to monitor the lymphocyte count for, at least, every 3 months during the DMF treatment. 3,24 In addition, it is recommended that DMF be suspended when lymphopenia (<500/mm 3 ) lasts >6 months. 3,24…”

“…2,4 However, the guidelines have not determined the positioning of DMF yet, because long-term safety data are missing. 3,24 Post-marketing data from Italy showed a better clinical and radiological outcome in treatment-na€ ıve patients (started DMF as first treatment) compared with patients who switched from other DMD to DMF. 31 The positioning of this drug in Japan will be determined after longterm efficacy and safety are available.…”

Systematic review and network meta‐analysis comparing ofatumumab with other disease‐modifying therapies available in Japan for the treatment of patients with relapsing multiple sclerosis

“…Recent treatment advancements have led to the availability of numerous disease‐modifying therapies (DMTs) for RMS/RRMS. Many DMTs are approved for use in the US and/or EU by the United States Food and Drug Administration (FDA) and European Medicines Agency; however, only seven DMTs are currently available for RRMS in Japan: dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta‐1a (IFNβ‐1a), interferon beta‐1b (IFNβ‐1b), natalizumab, and ofatumumab 9–11 . The 2017 treatment guidelines from the Japanese Society of Neurology recommend early introduction of a DMT in patients with RRMS to reduce/prevent irreversible disability progression over time 9 .…”