Efficacy of dimethyl fumarate in Japanese multiple sclerosis patients: interim analysis of randomized, double-blind APEX study and its open-label extension

T Kondo, I Kawachi, Y Onizuka, K Hiramatsu, M Hase, J Yun, A Matta, S Torii, T Kondo, I Kawachi, Y Onizuka, K Hiramatsu, M Hase, J Yun, A Matta, S Torii

Abstract

Background: Current data for the use of dimethyl fumarate (DMF) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS) is limited.

Objectives: To assess the efficacy of DMF in Japanese patients with RRMS.

Methods: The phase 3, multinational APEX study (ClinicalTrials.gov identifier: NCT01838668) consisted of two parts: a 24-week double-blind part where subjects were randomized to receive DMF 240 mg or placebo twice daily in East Asian and Eastern European countries, and an open-label extension part where all subjects received DMF. The primary endpoint was the total number of new gadolinium-enhancing lesions in Weeks 12-24. In this interim analysis, we report efficacy data in the Japanese subgroup (DMF n = 56; placebo n = 58) over 72 weeks, including an extension phase.

Results: DMF reduced the total number of new gadolinium-enhancing lesions in Weeks 12-24 by 85% versus placebo (p < 0.0001). At Week 24, the annualized relapse rate was also reduced by 48% with DMF, versus placebo. DMF reduced the probability of relapse from Week 8 and was sustained. The number of gadolinium-enhancing lesions was maintained through 72 weeks.

Conclusions: DMF demonstrated sustained efficacy in this Japanese subgroup. The results were consistent with those observed in studies of DMF enrolling primarily Caucasian patients.

Keywords: APEX; Japanese patients; delayed release; dimethyl fumarate; efficacy; relapsing–remitting multiple sclerosis.

Figures

Figure 1.
Figure 1.
CONSORT diagram of the study design.
Figure 2.
Figure 2.
The number of new gadolinium-enhancing (Gd+) lesions at (a) Weeks 12–24 and (b) Weeks 0–24. CI, confidence interval; DMF, dimethyl fumarate.
Figure 3.
Figure 3.
Kaplan–Meier estimate of the probability of relapse in Parts I and II of the APEX study, up to Week 72, for Japanese subjects in placebo/dimethyl fumarate (DMF) and DMF/DMF groups.
Figure 4.
Figure 4.
Expanded Disability Status Scale (EDSS) of Japanese subjects over 72 weeks in both Parts I and II. DMF, dimethyl fumarate.

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