Key result
Delayed-release dimethyl fumarate significantly reduced the annualized relapse rate compared to placebo in RRMS patients previously treated with interferon (rate ratio 0.55; 95% CI 0.40-0.77).
Why the study?
Does delayed-release dimethyl fumarate reduce annualized relapse rate in patients with relapsing-remitting multiple sclerosis previously treated with interferon beta?
RCT (n=341)
randomized
Does delayed-release dimethyl fumarate reduce annualized relapse rate in patients with relapsing-remitting multiple sclerosis previously treated with interferon beta?
Relative Risk: 0.55 (95% CI 0.4–0.77)
In patients with RRMS previously treated with interferon, delayed-release dimethyl fumarate significantly reduces relapse rates and MRI lesion burden over 2 years.
DMF reduced relapses and MRI activity after prior IFN in RRMS; extends Phase 3 data to this subgroup but remains hypothesis-generating.
PURPOSE: In Phase III studies (DEFINE [Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting MS]/CONFIRM [Comparator and an Oral Fumarate in Relapsing-Remitting Multiple Sclerosis]), delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS). Post hoc analyses of integrated data from DEFINE/CONFIRM were conducted to evaluate the effect of DMF in patients previously treated with interferon (IFN) beta. METHODS: Patients (age 18-55 years; Expanded Disability Status Scale score, 0-5.0) were randomized to receive DMF 240 mg BID or TID, placebo, or glatiramer acetate (CONFIRM only) for up to 2 years. Previous IFN users received at least 1 IFN treatment >3 months before randomization. Data for DMF 240 mg BID (approved dosing regimen) are reported. FINDINGS: In the integrated intention-to-treat population, 172 and 169 patients receiving DMF or placebo, respectively, had received ≥1 prior IFN. In this subgroup, significant reductions with DMF versus placebo were observed for the annualized relapse rate (rate ratio, 0.55 [95% CI, 0.40-0.77]), new/newly enlarging T2-hyperintense lesions (lesion mean ratio, 0.16 [95% CI, 0.09-0.29]), odds of having more gadolinium-enhancing lesions (odds ratio, 0.17 [95% CI, 0.07-0.44]), and new T1-hypointense lesions (lesion mean ratio, 0.25 [95% CI, 0.14-0.45]). Median Expanded Disability Status Scale scores remained stable during the study period. Adverse events associated with DMF included flushing and gastrointestinal events. IMPLICATIONS: In this post hoc analysis in patients with previous IFN treatment, DMF demonstrated significant efficacy over 2 years versus placebo and an adverse event profile consistent with the overall population of DEFINE/CONFIRM. ClinicalTrials.gov identifiers: DEFINE, NCT00420212; and CONFIRM, NCT00451451.
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Fernández et al. (2017) conducted an RCT in relapsing-remitting multiple sclerosis (n=341). delayed-release dimethyl fumarate vs. placebo was evaluated on annualized relapse rate (rate ratio 0.55, 95% CI 0.40-0.77). Delayed-release dimethyl fumarate significantly reduced the annualized relapse rate compared to placebo in RRMS patients previously treated with interferon (rate ratio 0.55; 95% CI 0.40-0.77).
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