Effect of Alfacalcidol on Fatigue in MS Patients: A Randomized, Double-Blind Study (S23.004)

OBJECTIVE: To evaluate the effect of vitamin D analogue, alfacalcidol, on multiple sclerosis (MS)-related fatigue. BACKGROUND: Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS), not efficiently responsive to current therapeutic agents. DESIGN/METHODS: A single site randomized double-blind placebo-controlled study. Patients suffering from significant fatigue were enrolled and randomized to parallel treatment arms: alfacalcidol (1 mcg) or placebo once daily for 6 months. The effect of treatment on fatigue and quality of life was evaluated using the fatigue impact scale (FIS) and RAYS quality of life (QOL) scale. RESULTS: One-hundred and fifty-eight MS patients (mean age 41.1+9.2 years, mean disease duration 6.2+5.5 years, 92% with relapsing-remitting disease) suffering from significant fatigue were included in the study. The baseline mean FIS score was 77.0+25.9 and the mean Expanded Disability Status Scale was 2.6+2.6. There was no difference in baseline FIS total score between the placebo and the (N=78) and the alfacalcidol (N=80) treatment arms. At study completion, there was a significant decrease in FIS total score within each treatment arm (p<0.001); however the mean relative decrease from baseline was statistically significantly greater in the alfacalcidol treatment arm compared with the placebo arm (-41.6%±39.0 versus -27.4%±45.6, p=0.007). QOL improved significantly with alfacalcidol treatment in the psychological sub-scale (p=0.033) and in the social sub-scale (p=0.043). Alfacalcidol-treated patients had a reduced number of relapses (p<0.001) and no serious adverse events were recorded. CONCLUSIONS: Alfacalcidol is a safe and effective treatment strategy for treating fatigue in MS. Study Supported by: This study was supported by a research grant from Teva Ltd., Israel. Disclosure: Dr. Barak has received personal compensation for activities with JC Health Care, Biotis and Lundbeck Research USA, Inc. Dr. Barak has received research support from Merck & Co. Inc., Lundbeck Research USA, Inc., and GlaxoSmithKlyne, Inc. Dr. Magalashvili has nothing to disclose. Dr. Dolev Dolgopiat has nothing to disclose. Dr. Ladkani has received personal compensation for activities with Teva Neuroscience. Dr. Ladkani holds stock and/or stock options in Teva Neuroscience which sponsored research in which Dr. Ladkani was involved as an investigator. Dr. Nitzani has nothing to disclose. Dr. Mazor has received personal compensation for activities with Teva Neuroscience. Dr. Achiron has received personal compensation for activities with Teva Neuroscience and Novartis. Dr. Achiron has received research support from Bayer-Schering Pharma, Biogen Idec, and Teva Neuroscience.