Nakamura, Kunio;
Mokliatchouk, Oksana;
Arnold, Douglas L;
Yousry, Tarek A;
Kappos, Ludwig;
Richert, Nancy;
Ayling-Rouse, Katherine;
... Fisher, Elizabeth; + view all
(2022)
Effects of Dimethyl Fumarate on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: Pooled Analysis Phase 3 DEFINE and CONFIRM Studies.
Frontiers in Neurology
, 13
, Article 809273. 10.3389/fneur.2022.809273.
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Abstract
OBJECTIVE: In the pivotal DEFINE and CONFIRM trials for dimethyl fumarate (DMF), patterns of brain volume changes were different, potentially due to low sample sizes and because MRIs were analyzed at two different reading centers. We evaluated effects of DMF on brain volume change in patients with multiple sclerosis (MS) through reanalysis of pooled images from DEFINE/CONFIRM trials in one reading center. METHODS: MRIs from DEFINE/CONFIRM at weeks 0, 24, 48, and 96 from patients randomized to twice-daily DMF or placebo (PBO) were reanalyzed at the Cleveland Clinic to measure brain parenchymal fraction (BPF). To account for pseudoatrophy, brain volume estimates were re-baselined to calculate changes for weeks 48–96. RESULTS: Across studies, 301 and 314 patients receiving DMF and PBO, respectively, had analyzable MRIs. In weeks 0–48, mean ± SE percentage change in BPF was −0.44 ± 0.04 vs. −0.34 ± 0.04% in DMF vs. PBO, respectively, whereas in weeks 48–96, mean ± SE percentage change in BPF was −0.27 ± 0.03 vs. −0.41 ± 0.04% in DMF vs. PBO, respectively. The mixed-effect model for repeated measures showed similar results: in weeks 48–96, estimated change (95% confidence interval) in BPF was −0.0021 (−0.0027, −0.0016) for DMF vs. −0.0033 (−0.0039, −0.0028) for PBO (35.9% reduction; p = 0.0025). CONCLUSIONS: The lower rate of whole brain volume loss with DMF in this pooled BPF analysis in the second year vs. PBO is consistent with its effects on relapses, disability, and MRI lesions. Brain volume changes in the first year may be explained by pseudoatrophy effects also described in other MS clinical trials.
| Type: | Article |
|---|---|
| Title: | Effects of Dimethyl Fumarate on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: Pooled Analysis Phase 3 DEFINE and CONFIRM Studies |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fneur.2022.809273 |
| Publisher version: | https://doi.org/10.3389/fneur.2022.809273 |
| Language: | English |
| Additional information: | © 2022 Nakamura, Mokliatchouk, Arnold, Yousry, Kappos, Richert, Ayling-Rouse, Miller and Fisher. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Dimethyl fumarate, multiple sclerosis, brain parenchymal fraction, pseudoatrophy, brain volume loss |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10152914 |
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