PMID- 16796584
OWN - NLM
STAT- MEDLINE
DCOM- 20060905
LR  - 20151119
IS  - 1351-5101 (Print)
IS  - 1351-5101 (Linking)
VI  - 13
IP  - 6
DP  - 2006 Jun
TI  - Oral fumaric acid esters for the treatment of active multiple sclerosis: an 
      open-label, baseline-controlled pilot study.
PG  - 604-10
AB  - An exploratory, prospective, open-label study of fumaric acid esters (FAE, 
      Fumaderm(R)) was conducted in patients with relapsing-remitting multiple 
      sclerosis (RRMS). The study consisted of the following four phases: 6-week 
      baseline, 18-week treatment (target dose of 720 mg/day), 4-week washout, and a 
      second 48-week treatment phase (target dose of 360 mg/day). Ten patients with an 
      Expanded Disability Status Scale (EDSS) score of 2.0-6.0 and at least one 
      gadolinium-enhancing (Gd+) lesion on T1-weighted magnetic resonance imaging (MRI) 
      brain scans participated in the study. Safety was assessed by adverse events 
      (AEs), blood chemistry/hematology, electrocardiogram, and urinalysis. The primary 
      efficacy outcomes were number and volume of Gd+ lesions. Other clinical outcomes 
      included EDSS score, ambulation index (AI), and nine-hole peg test (9-HPT). 
      Effects of FAE on intracellular cytokine profiles, T-cell apoptosis, and soluble 
      adhesion molecules were also assessed. Three patients withdrew during the first 3 
      weeks of the study because of side effects, non-compliance, and follow-up loss. 
      The most common AEs were gastrointestinal symptoms and flushing; all AEs were 
      reported as mild and reversible. FAE produced significant reductions from 
      baseline in number (P < 0.05) and volume (P < 0.01) of Gd+ lesions after 18 weeks 
      of treatment; this effect persisted during the second treatment phase at half the 
      target dose after the 4-week washout period. EDSS scores, AI, and 9-HPT remained 
      stable or slightly improved from baseline in all patients. Measures of T-cell 
      function demonstrated alterations in cytokines and circulating tumor necrosis 
      factor. The results of this exploratory study suggest that further studies of FAE 
      in patients with MS are warranted.
FAU - Schimrigk, S
AU  - Schimrigk S
AD  - Department of Neurology, St. Josef Hospital, Ruhr Universitat Bochum, Germany. 
      sebastian.k.schimrigk@rub.de
FAU - Brune, N
AU  - Brune N
FAU - Hellwig, K
AU  - Hellwig K
FAU - Lukas, C
AU  - Lukas C
FAU - Bellenberg, B
AU  - Bellenberg B
FAU - Rieks, M
AU  - Rieks M
FAU - Hoffmann, V
AU  - Hoffmann V
FAU - Pohlau, D
AU  - Pohlau D
FAU - Przuntek, H
AU  - Przuntek H
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Neurol
JT  - European journal of neurology
JID - 9506311
RN  - 0 (Cytokines)
RN  - 0 (Fumarates)
RN  - 0 (Immunosuppressive Agents)
RN  - FO2303MNI2 (Dimethyl Fumarate)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Apoptosis/drug effects
MH  - Cytokines/metabolism
MH  - Dimethyl Fumarate
MH  - Disability Evaluation
MH  - Electroencephalography/methods
MH  - Female
MH  - Follow-Up Studies
MH  - Fumarates/*administration & dosage
MH  - Humans
MH  - Immunosuppressive Agents/*administration & dosage
MH  - Magnetic Resonance Imaging/methods
MH  - Male
MH  - Multiple Sclerosis/*drug therapy/pathology/physiopathology
MH  - Pilot Projects
MH  - Prospective Studies
MH  - Statistics, Nonparametric
MH  - T-Lymphocytes/drug effects
MH  - Time Factors
EDAT- 2006/06/27 09:00
MHDA- 2006/09/06 09:00
CRDT- 2006/06/27 09:00
PHST- 2006/06/27 09:00 [pubmed]
PHST- 2006/09/06 09:00 [medline]
PHST- 2006/06/27 09:00 [entrez]
AID - ENE1292 [pii]
AID - 10.1111/j.1468-1331.2006.01292.x [doi]
PST - ppublish
SO  - Eur J Neurol. 2006 Jun;13(6):604-10. doi: 10.1111/j.1468-1331.2006.01292.x.