VANCOUVER, BC—Delayed-release dimethyl fumarate (DMF) was associated with significant reductions in confirmed disability progression (CDP) in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS), compared with placebo, presented J. Theodore Phillips, MD, PhD, FAAN, Baylor Institute for Immunology Research, Dallas, TX, at the 68th AAN Annual Meeting.
Summary scores (or z scores) and EDSS scores used to assess MS Functional Composite and disability progression have limitations in establishing clinically meaningful changes. “A potentially more reliable approach is to use a composite outcome measure and to define worsening as a prespecified decrease in any component score, and to show worsening in the same component at ≥2 subsequent time points.”
In order to assess the clinical effect of DMF on multicomponent composite measures in newly diagnosed patients with RRMS (from the DEFINE/CONFIRM studies), researchers randomized 444 newly diagnosed RRMS patients; 221 of whom received DMF (240mg twice or three times daily) and 223 of whom received placebo. “Newly diagnosed” was defined as having received a diagnosis within 1 year prior to study entry, and treatment-naïve or previously treated with corticosteroids alone. The efficacy endpoint was outcome measures of the composite-CDP and score changes associated with worsening; assessments were made at 12-week intervals from baseline.
Previous analyses of Phase 3 trials, DEFINE and CONFIRM, had shown DMF to reduce confirmed disability progression. In this study, the researchers added more multiple neuroperformance components with an aim to enhance the past findings. Rates measured—starting at a worsening in baseline—came from a variety of disability outcomes including; Expanded Disability Status Scale (EDSS), 9-hole peg test (9HPT), Paced Auditory Serial Addition Test (PASAT); ≥10-letter on Visual Function Test (VFT).
Results showed that the DMF 240mg twice daily significantly reduced the risks for 12- and 24-week CDP compared with placebo at 2 years, as measured by EDSS or worsening of any other disability outcomes measured (T25FW, 9HPT, PASAT, VFT). In addition, the overall composite-CDP risk was significantly lowered as measured by worsening in any of the 5 components for 12-week (HR 0.68; P=0.0198) or 24-week (HR 0.56; P=0.0053) CDP, compared to placebo in newly diagnosed RRMS patients treated with DMF 240mg twice daily.
“Our results show that for newly diagnosed patients, DMF can help significantly reduce disability progression compared to placebo,” concluded Dr. Phillips. The findings, consistent with previous data, showed statistically significant clinical benefits with DMF 240mg twice daily vs. placebo for all components of the composite-CDP.
Dr. Phillips and other members of this researcher team disclosed receiving consulting fees from Biogen who supported the study.