Dataset Information

Efficacy and safety of dimethyl fumarate in treatment-naive Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

ABSTRACT: Background:The use of dimethyl fumarate has not been reported in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis. Objectives:The purpose of this study was to evaluate the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis. Methods:APEX was a phase 3, multinational trial, which consisted of a 24-week, randomized (1:1), double-blind study where patients received dimethyl fumarate 240 mg or placebo twice daily, followed by an open-label extension where all patients received dimethyl fumarate 240 mg. The primary endpoints were the total number of new gadolinium-enhancing (Gd+) lesions in Weeks 12-24 (Part I) and long-term safety (Part II). This post-hoc subgroup analysis evaluated the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis (n=52) up to Week 72 (24 weeks Part I and 48 weeks Part II). Results:Dimethyl fumarate reduced the mean total number of new gadolinium-enhancing lesions at Weeks 12-24 by 94% versus placebo; the number of patients who had a relapse over 24 weeks was reduced by 72%. Adverse events leading to discontinuation of the study drug were reported in 9% of patients receiving placebo/dimethyl fumarate and 4% of patients in dimethyl fumarate/dimethyl fumarate. Conclusions:Dimethyl fumarate demonstrated sustained efficacy and acceptable tolerability in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis for 72 weeks.

SUBMITTER: Mori M

PROVIDER: S-EPMC6558550 | biostudies-literature | 2019 Apr-Jun

REPOSITORIES: biostudies-literature

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Efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

Mori Masahiro M Ohashi Takashi T Onizuka Yasuhiro Y Hiramatsu Katsutoshi K Hase Masakazu M Yun Jang J Matta André A Torii Shinichi S

Multiple sclerosis journal - experimental, translational and clinical 20190401 2

<h4>Background</h4>The use of dimethyl fumarate has not been reported in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis.<h4>Objectives</h4>The purpose of this study was to evaluate the efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with relapsing-remitting multiple sclerosis.<h4>Methods</h4>APEX was a phase 3, multinational trial, which consisted of a 24-week, randomized (1:1), double-blind study where patients received dimethyl fumar ...[more]

PMID: 31218077

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Project description:BackgroundPatients with multiple sclerosis (MS) experience relapses and sustained disability progression. Since 2004, the number of disease-modifying therapies (DMTs) for MS has grown substantially. As a result, patients, healthcare providers, and insurers are increasingly interested in comparative efficacy and safety evaluations to distinguish between treatment options, but head-to-head studies between DMTs are limited.ObjectiveThe aim of the current study was to compare efficacy and safety outcomes with the DMTs ozanimod and dimethyl fumarate (DMF) using a matching-adjusted indirect comparison (MAIC) to adjust for cross-trial differences in study design and population.MethodsA systematic literature review was performed to identify clinical studies evaluating the efficacy and safety of ozanimod compared with DMF. Individual patient-level data (IPD) for ozanimod were obtained from the SUNBEAM and RADIANCE Part B trials, and aggregate-level patient data (APD) for DMF were obtained from CONFIRM and DEFINE. A MAIC is used to weight IPD to APD based on important baseline patient characteristics considered to be effect modifiers or prognostic factors in order to balance the covariate distribution to establish more homogenous trial populations. Once trial populations are determined to be sufficiently homogenous, outcomes of interest are estimated and used to generate treatment effects between the weighted IPD and APD. We used MAIC methodology to compare efficacy and safety outcomes of interest between ozanimod 1.0 mg once daily (OD) and DMF 240 mg twice daily (BID), including confirmed disability progression (CDP) at 3 and 6 months, annualized relapse rate (ARR), proportion of patients relapsed, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.ResultsAfter matching patient data, baseline patient characteristics were balanced between patients receiving ozanimod and those receiving DMF. Compared with DMF, ozanimod demonstrated significantly improved CDP at 3 months (hazard ratio 0.67; 95% confidence interval [CI] 0.53-0.86), ARR (rate ratio [RR] 0.80; 95% CI 0.67-0.97), proportion of patients relapsed (odds ratio [OR] 0.66; 95% CI 0.52-0.83), overall AEs (OR 0.11; 95% CI 0.08-0.16), SAEs (OR 0.27; 95% CI 0.19-0.39), and discontinuations (OR 0.11; 95% CI 0.07-0.17). CDP at 6 months did not differ significantly between the two agents (RR 0.89; 95% CI 0.62-1.26).ConclusionsAfter adjustment of baseline patient characteristics, the MAIC demonstrated that the efficacy and safety of ozanimod 1.0 mg OD was superior to that of DMF 240 mg BID. Although a MAIC is less likely to produce biased estimates than a naïve or a standard indirect treatment comparison via a common comparator, limitations include potential confounding due to unobserved and thus unaccounted for baseline differences.

Dataset Information

Efficacy and safety of dimethyl fumarate in treatment-naive Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

Publications

Efficacy and safety of dimethyl fumarate in treatment-naïve Japanese patients with multiple sclerosis: Interim analysis of the randomized placebo-controlled study.

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