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

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.

Clinical use of dimethyl fumarate in multiple sclerosis treatment: an update to include China, using a modified Delphi method

“…Evidence for efficacy of DMF in the East Asian population comes primarily from Japan, which contributed the majority (80%) of the East Asian population ( n = 142) in the APEX study, followed by South Korea (14%). 48 , 49 A post hoc sub-analysis of Asian data from Fox et al 2 has also been performed, confirming treatment efficacy and positive benefit-risk balance. In general, treatment results are similar between East Asian and Caucasian/rest-of-the-world populations, although there is lower incidence of MS but potentially poorer prognosis in Asian populations, possibly due to increased frequency of spinal lesions in this population and incomplete resolution of first attacks.…”

“…The studies in East Asian patients used the same dose regimen and reported a consistent AE profile for DMF, as the pivotal trials, which largely included Caucasian patients. 16 , 48 – 50 No change in dosing is required for this population.…”

“…The overall level of evidence for the efficacy of DMF was considered high, albeit with varying ratings for individual parameters. For relapse rate/annualized relapse rates (ARRs), radiological evidence of disease activity and disability progression, the data are derived from several large RCTs, meta-analyses and systematic reviews, 25 – 28 , 49 , 51 – 53 and have been incorporated into guidelines from all major MS organizations, including in Japan. 16 , 54 – 56 The pivotal clinical trials most convincingly demonstrated improvements in relapse rate/ARR with DMF treatment.…”

“…Early ( versus later) initiation of an effective DMT is linked to better long-term outcomes for patients with MS (see efficacy statements, Figure 3 , Statements 7–9), exemplified by achieving NEDA-3 with DMF. 49 , 54 , 55 , 58 , 151 Treatment inertia may delay switching, and latency to initiation of an effective therapy may result in poorer outcomes, meaning that in addition to initiating DMTs early, switches should be considered if a therapy has proved intolerable or has shown a lack of efficacy in the judgement of the treatment team. 29 , 142 …”

Diroximel Fumarate as a Novel Oral Immunomodulating Therapy for Relapsing Forms of Multiple Sclerosis: A Review on the Emerging Data

“…Results of APEX, a pivotal trial in a predominantly East Asian population, were reassuring of those seen in DEFINE and CONFIRM. 78 Real-world evidence corroborates the efficacy of DR DMF in RRMS concerning lowering the relapse rate and slowing disability progression. A recent review article identified several observational studies.…”