DIR Return Create A Forum - Home
---------------------------------------------------------
MS Speaks
HTML https://msspeaks.createaforum.com
---------------------------------------------------------
*****************************************************
DIR Return to: TECFIDERA (dimethyl fumarate, BG-12, Fumaderm)
*****************************************************
#Post#: 630--------------------------------------------------
(Abst.) Dimethyl fumarate in the treatment of RRMS: overview
By: agate Date: January 24, 2015, 6:41 pm
---------------------------------------------------------
From Therapeutic Advances in Neurological Disorders, January 6,
2015:
[quote]Dimethyl fumarate in the treatment of relapsing–remitting
multiple sclerosis: an overview
Roberto Bomprezzi
Department of Neurology, University of Massachusetts, 55 Lake
Avenue North, Worcester, MA 01655, USA
rbomprez@gmail.com
Multiple sclerosis (MS) shares an immune-mediated origin with
psoriasis. Long-term safety and efficacy data generated in
Europe from usage of fumaric acid formulations in the latter
disease constituted grounds to investigate their effects in MS
patients. Dimethyl fumarate (DMF) was found to be the active
principle in those formulations and in vitro studies have
demonstrated that DMF has immune-modulatory properties exerted
through abilities to divert cytokine production toward a Th2
profile, both on lymphocytes and microglial cells.
More importantly, DMF was discovered to impact the
anti-oxidative stress cell machinery promoting the transcription
of genes downstream to the activation of the nuclear factor
(erythroid derived 2)-like2 (NRF2). DMF exposure increases the
cytosol concentrations of NRF2, which besides immune regulatory
effects, has the potential for cytoprotection on glial cells,
oligodendrocytes and neurons.
Extensive and rigorous clinical trials have assessed the
efficacy and safety of DMF at the dose of 240 mg twice and three
times a day in relapsing-remitting MS patients during one phase
IIb and two phase III trials. Robust, positive results were
obtained across a number of clinical and paraclinical
parameters.
In one study (DEFINE), the relative reductions of the adjusted
annualized relapse rate of the low and high dose regimens in
comparison with placebo were 53% and 48%, respectively
(p < 0.001 for both comparisons).
In the other trial (CONFIRM), DMF decreased the annualized
relapse rate in comparison with placebo by 44% in the lower and
by 51% in higher dosage group (also p < 0.001). The number and
size of lesions as detected by magnetic resonance imaging were
also significantly decreased in comparison with the patients
receiving DMF at every dosage. Multiple post hoc and subgroup
analyses corroborated the clinical data, rendering DMF an
appealing medication whose potential for impacting the
degenerative aspects of MS remains to be explored.[/quote]
*****************************************************