Author Of 1 Presentation
P0232 - Safety and efficacy of dimethyl fumarate in patients with primary progressive multiple sclerosis: A double-blind, randomized phase 2 trial (ID 1651)
Abstract
Background
Dimethyl fumarate (DMF) has been shown to have immunomodulatory and neuroprotective properties that may inhibit disease progression in patients with progressive multiple sclerosis (MS). Increased levels of neurofilament light chain (NFL) in blood or cerebrospinal fluid (CSF) indicates neuroaxonal damage, and concentrations significantly decrease upon treatment with DMF in relapsing-remitting MS.
Objectives
To evaluate the efficacy and safety of DMF therapy in primary progressive MS (PPMS) in a randomized placebo-controlled phase 2 trial with change in NFL in CSF as primary outcome.
Methods
The study was conducted at Copenhagen University Hospital Rigshospitalet, Denmark. Participants with PPMS were randomly assigned 1:1 to treatment with 240 mg DMF twice daily or placebo for 48 weeks. Primary endpoint was change in NFL in CSF from screening to week 48. Secondary endpoints were change in CSF concentrations of myelin basic protein (MBP), B-cell maturation antigen, chitinase-3-like-1, soluble CD27, soluble CD14, IgG-index, and albumin quotient; change in fractional anisotropy of normal-appearing white matter, magnetization transfer ratio of lesions, mean thalamic volume, difference in number of new or enlarged T2 lesions, and percentage brain volume change; and change in expanded disability status scale, timed 25-foot walk test, 9-hole peg test, and symbol digit modalities test. ClinialTrials.gov: NCT02959658.
Results
54 patients were randomized from December 2016 to January 2018 to placebo (n=27) or DMF treatment (n=27). Mean age was 55 years (SD 6·1), mean disease duration was 14 years (SD 9·4), median EDSS was 4·0 (range 2·0 – 6·5) and mean concentration of NFL in CSF was 844 ng/L (SD 631 ng/L). Twenty-six participants (96%) in the dimethyl fumarate group and 24 participants (89%) in the placebo group completed the randomized phase. Mean change in CSF concentrations of NFL did not differ between groups (99 ng/l; 95% CI -292 – 491 ng/l) but we did observe a decrease in CSF concentrations of MBP in patients treated with DMF compared with placebo. Common infections were more frequent in the DMF group. Serious adverse events were comparable between groups.
Conclusions
DMF treatment for 48 weeks did not reduce CSF concentrations of NFL in patients with PPMS but might reduce demyelination as assessed by the CSF concentration of MBP.
Presenter Of 1 Presentation
P0232 - Safety and efficacy of dimethyl fumarate in patients with primary progressive multiple sclerosis: A double-blind, randomized phase 2 trial (ID 1651)
Abstract
Background
Dimethyl fumarate (DMF) has been shown to have immunomodulatory and neuroprotective properties that may inhibit disease progression in patients with progressive multiple sclerosis (MS). Increased levels of neurofilament light chain (NFL) in blood or cerebrospinal fluid (CSF) indicates neuroaxonal damage, and concentrations significantly decrease upon treatment with DMF in relapsing-remitting MS.
Objectives
To evaluate the efficacy and safety of DMF therapy in primary progressive MS (PPMS) in a randomized placebo-controlled phase 2 trial with change in NFL in CSF as primary outcome.
Methods
The study was conducted at Copenhagen University Hospital Rigshospitalet, Denmark. Participants with PPMS were randomly assigned 1:1 to treatment with 240 mg DMF twice daily or placebo for 48 weeks. Primary endpoint was change in NFL in CSF from screening to week 48. Secondary endpoints were change in CSF concentrations of myelin basic protein (MBP), B-cell maturation antigen, chitinase-3-like-1, soluble CD27, soluble CD14, IgG-index, and albumin quotient; change in fractional anisotropy of normal-appearing white matter, magnetization transfer ratio of lesions, mean thalamic volume, difference in number of new or enlarged T2 lesions, and percentage brain volume change; and change in expanded disability status scale, timed 25-foot walk test, 9-hole peg test, and symbol digit modalities test. ClinialTrials.gov: NCT02959658.
Results
54 patients were randomized from December 2016 to January 2018 to placebo (n=27) or DMF treatment (n=27). Mean age was 55 years (SD 6·1), mean disease duration was 14 years (SD 9·4), median EDSS was 4·0 (range 2·0 – 6·5) and mean concentration of NFL in CSF was 844 ng/L (SD 631 ng/L). Twenty-six participants (96%) in the dimethyl fumarate group and 24 participants (89%) in the placebo group completed the randomized phase. Mean change in CSF concentrations of NFL did not differ between groups (99 ng/l; 95% CI -292 – 491 ng/l) but we did observe a decrease in CSF concentrations of MBP in patients treated with DMF compared with placebo. Common infections were more frequent in the DMF group. Serious adverse events were comparable between groups.
Conclusions
DMF treatment for 48 weeks did not reduce CSF concentrations of NFL in patients with PPMS but might reduce demyelination as assessed by the CSF concentration of MBP.