Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study.

Abstract

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.

• Authors: S Schimrigk, N Brune, K Hellwig, C Lukas, B Bellenberg, M Rieks, V Hoffmann, D Pöhlau, H Przuntek
• Journal: European journal of neurology (Eur J Neurol) Vol. 13 Issue 6 Pg. 604-10 (Jun 2006) ISSN: 1351-5101 [Print] England
• PMID: 16796584 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• Fumarates
• Immunosuppressive Agents
• Dimethyl Fumarate

Topics

• Administration, Oral
• Adult
• Apoptosis (drug effects)
• Cytokines (metabolism)
• Dimethyl Fumarate
• Disability Evaluation
• Electroencephalography (methods)
• Female
• Follow-Up Studies
• Fumarates (administration & dosage)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Magnetic Resonance Imaging (methods)
• Male
• Multiple Sclerosis (drug therapy, pathology, physiopathology)
• Pilot Projects
• Prospective Studies
• Statistics, Nonparametric
• T-Lymphocytes (drug effects)
• Time Factors