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

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Abstract
An exploratory, prospective, open‐label study of fumaric acid esters (FAE, Fumaderm®) 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.

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