Efficacy and Tolerability of Delayed-release Dimethyl Fumarate in Black, Hispanic, and Asian Patients with Relapsing-Remitting Multiple Sclerosis: Post Hoc Integrated Analysis of DEFINE and CONFIRM

Robert J Fox, Ralf Gold, J Theodore Phillips, Macaulay Okwuokenye, Annie Zhang, Jing L Marantz, Robert J Fox, Ralf Gold, J Theodore Phillips, Macaulay Okwuokenye, Annie Zhang, Jing L Marantz

Abstract

Introduction: Clinical course and treatment response may vary according to race/ethnicity in multiple sclerosis (MS) patients. Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) demonstrated significant efficacy and a favorable benefit-risk profile in relapsing-remitting MS (RRMS) patients in the 2-year phase III DEFINE/CONFIRM studies.

Methods: In this post hoc analysis of integrated data from DEFINE/CONFIRM, we assessed clinical efficacy and safety/tolerability in black, Hispanic, and Asian patients treated with DMF 240 mg twice daily (approved dosage) or placebo. Eligible patients were 18-55 years of age with an Expanded Disability Status Scale score of 0-5.0. In the integrated intention-to-treat population, 769 and 771 patients were treated with DMF or placebo, respectively, of whom 10 and 19 were black, 31 and 23 were Hispanic, and 66 and 70 were Asian.

Results: In the black, Hispanic, and Asian subgroups, DMF was associated with lower annualized relapse rates at 2 years compared with placebo [rate ratio (95% confidence interval (CI)), 0.05 (0.00-1.07); 0.31 (0.10-0.95); and 0.64 (0.30-1.34), respectively]. The percentage of black, Hispanic, and Asian patients with 12-week confirmed disability progression was lower with DMF (43%, 8%, and 20%, respectively) compared with placebo [57%, 30%, and 25%, respectively; hazard ratio (95% CI), 0.53 (0.02-1.39); 0.17 (0.00-0.60); and 0.71 (0.32-1.58), respectively]. The safety/tolerability profile of DMF was generally consistent with that in the overall population of DEFINE/CONFIRM. The incidence of adverse events leading to treatment discontinuation in black, Hispanic, and Asian patients was 2/10, 2/31, and 3/66, respectively, with DMF, and 2/19, 1/23, and 8/70, respectively, with placebo.

Conclusion: DMF may be an efficacious treatment with a favorable benefit-risk profile in black, Hispanic, and Asian patients with RRMS. Further clinical studies are needed to characterize differences in MS presentation and treatment outcomes across ethnic and racial groups.

Funding: Biogen.

Trial registration: DEFINE: ClinicalTrials.gov identifier NCT00420212; CONFIRM ClinicalTrials.gov identifier NCT00451451.

Keywords: Delayed-release dimethyl fumarate; Efficacy; Ethnicity; Race; Relapsing-remitting multiple sclerosis; Tolerability.

Figures

Fig. 1
Fig. 1
Adjusted annualized relapse rate (ARR) at 2 years in the intention-to-treat (ITT) population of CONFIRM and DEFINE and across ethnic subgroups (integrated analysis of DEFINE and CONFIRM). aCI denotes confidence interval. bDMF denotes delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF). cCI denotes credible interval
Fig. 2
Fig. 2
Clinical efficacy with delayed-release DMF. a Rate ratio for the adjusted annualized relapse rate (ARR) at 2 years. b Hazard ratio for proportion of patients with relapse at 2 years. c Hazard ratio for 12-week confirmed disability progression at 2 years. aDMF denotes delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) vs. placebo in ethnic subgroups (integrated analysis of DEFINE and CONFIRM). bNumber of patients treated with DMF twice daily/placebo. cIntervals represent 95% confidence intervals for the overall ethnic subgroup and Asian patients with multiple sclerosis (MS) and 95% credible intervals for black and Hispanic patients with MS. CI confidence/credible interval, ITT intention-to-treat

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