Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study.
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.
Schimrigk
S
S
Department of Neurology, St. Josef Hospital, Ruhr Universität Bochum, Germany. sebastian.k.schimrigk@rub.de
Brune
N
N
Hellwig
K
K
Lukas
C
C
Bellenberg
B
B
Rieks
M
M
Hoffmann
V
V
Pöhlau
D
D
Przuntek
H
H
D000284:Administration, Oral; D000328:Adult; D017209:Apoptosis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D000069462:Dimethyl Fumarate; D004185:Disability Evaluation; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D005650:Fumarates / Q000008:administration & dosage*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D010865:Pilot Projects; D011446:Prospective Studies; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D016207:Cytokines; D005650:Fumarates; D007166:Immunosuppressive Agents; D000069462:Dimethyl Fumarate