RT Journal Article
SR Electronic
T1 Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis
JF Neurology - Neuroimmunology Neuroinflammation
JO Neurol Neuroimmunol Neuroinflamm
FD Lippincott Williams & Wilkins
SP e1037
DO 10.1212/NXI.0000000000001037
VO 8
IS 5
A1 Helene Højsgaard Chow
A1 Jacob Talbot
A1 Henrik Lundell
A1 Camilla Gøbel Madsen
A1 Lisbet Marstrand
A1 Theis Lange
A1 Mie Reith Mahler
A1 Sophie Buhelt
A1 Rikke Holm Hansen
A1 Morten Blinkenberg
A1 Jeppe Romme Christensen
A1 Per Soelberg Sørensen
A1 Marina Rode von Essen
A1 Hartwig Roman Siebner
A1 Finn Sellebjerg
YR 2021
UL http://nn.neurology.org/content/8/5/e1037.abstract
AB Background and Objective To study whether dimethyl fumarate is superior to placebo in decreasing CSF concentrations of neurofilament light chain (NFL) in patients with primary progressive MS (PPMS).Methods In the double-blind, placebo-controlled phase 2 study dimethyl FUMArate treatment in Progressive Multiple Sclerosis (FUMAPMS), patients with PPMS were randomly assigned to treatment with 240 mg dimethyl fumarate or placebo in a 1:1 ratio for 48 weeks. The primary endpoint was change in concentration of NFL in the CSF. Secondary endpoints included other CSF biomarkers and clinical and MRI measures. Efficacy was evaluated for the full data set by multiple imputations to account for missing data. Safety was assessed for the full data set.Results Fifty-four patients (mean age 54.9 years [SD 6.1], median Expanded Disability Status Scale 4.0 [nterquartile range 4.0–6.0], disease duration 14.1 [SD 9.4], and 21 [39%] female) were randomized to either placebo (n = 27) or dimethyl fumarate (n = 27) therapy. At screening CSF concentrations, adjusted for age and sex, of NFL, myelin basic protein (MBP), soluble CD27, chitinase 3-like 1, and B-cell maturation antigen were higher than in a group of symptomatic controls. Twenty-six patients (96%) in the dimethyl fumarate group and 24 patients (89%) in the placebo group completed the randomized phase. Mean change in CSF concentrations of NFL did not differ between groups (mean difference 99 ng/L; 95% CI −292 to 491 ng/L). MBP in CSF decreased in the treatment group (−182 ng/L, 95% CI −323 to −41 ng/L compared with placebo). The difference observed in the multiple imputation data set was not significant in a per protocol analysis. This was nominally significant in the multiple imputation data set but not in the per protocol analysis This was not found in the per protocol analysis Other secondary and tertiary outcomes were not affected. Various infections, lymphopenia, flushing, and gastrointestinal side effects were more frequent in the dimethyl fumarate group. Serious adverse events were similar between groups.Discussion Dimethyl fumarate treatment for 48 weeks had no effect on any of the investigated efficacy measures in patients with PPMS. We did not observe adverse events not anticipated for dimethyl fumarate treatment.Trial Registration Information Clinicaltrials.gov identifier NCT02959658.Classification of Evidence This study provides Class I evidence that for patients with PPMS, dimethyl fumarate treatment has no effect on CSF NFL levels compared with placebo treatment.9HPT=Nine-Hole Peg Test; BCMA=B-cell maturation antigen; CHI3L1=chitinase 3-like 1; CTCAE=Common Terminology Criteria for Adverse Events; EDSS=Expanded Disability Status Scale; MBP=myelin basic protein; NFL=neurofilament light chain; PPMS=primary progressive MS; RRMS=relapsing-remitting MS; sCD14=soluble CD14; sCD27=soluble CD27; SDMT=Symbol Digit Modalities Test; SIMOA=single-molecule array; T25FW=Timed 25-Foot Walk