IngentaConnect Oral fumaric acid esters for the treatment of active multiple scl...

Authors: Schimrigk, S.; Brune, N.; Hellwig, K.¹; Lukas, C.¹; Bellenberg, B.¹; Rieks, M.; Hoffmann, V.¹; Pöhlau, D.¹; Przuntek, H.

Source: European Journal of Neurology, Volume 13, Number 6, June 2006 , pp. 604-610(7)

Publisher: Blackwell Publishing

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.

Keywords: fumaric acid esters; magnetic resonance imaging; multiple sclerosis; open-label study

Document Type: Research article

DOI: 10.1111/j.1468-1331.2006.01292.x

Affiliations: 1: Department of Neurology

The full text electronic article is available for purchase. You will be able to download the full text electronic article after payment.

$50.39 plus tax Refund Policy

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