PHILADELPHIA—Alfacalcidol, a synthetic analog of vitamin D, significantly reduces fatigue related to multiple sclerosis (MS), according to research presented at the 66th Annual Meeting of the American Academy of Neurology. The drug also may result in significant improvements in psychologic and social quality of life. No serious adverse events are associated with alfacalcidol, which appears to have a rate of adverse events similar to that of placebo.
In a six-month study, alfacalcidol reduced the number of acute relapses in patients with MS. This result suggests that fatigue, like relapses, is a symptom of disease activity, said Anat Achiron, MD, PhD, Director of the MS Center at the Sheba Medical Center in Tel Hashomer, Israel. “By decreasing fatigue and relapses, you can achieve the same goal,” she added.
Anat Achiron, MD, PhD
Comparing Alfacalcido With Placebo
The trial was designed as a two-stage process to enrich the study population with patients with MS whose fatigue is significant. Dr. Achiron and colleagues administered the Fatigue Severity Scale to 600 patients with relapsing-remitting MS to analyze the effect of alfacalcidol on MS-related fatigue. A total of 500 patients responded to the questionnaire, and 259 patients who gave a score of 3 or higher to the ninth item (ie, “Fatigue interferes with my work, family, or social life”) were included in the second stage of enrollment.
A total of 158 patients between ages 18 and 55 who had an Expanded Disability Status Scale (EDSS) score of 5 or lower and a Fatigue Impact Scale (FIS) score of 40 or higher were eligible. Of these patients, 80 were randomized to receive 1 µg/day of alfacalcidol, and 78 were randomized to placebo. All patients completed the FIS and RAYS quality of life questionnaire at baseline. Patients were treated for six months, at which point they completed the FIS and RAYS questionnaires again. The researchers conducted follow-up visits with the patients two months after the cessation of treatment.
The primary end point was improvement in FIS score, which was defined as a 30% decrease. The secondary end points were change in the RAYS quality of life scale, change in EDSS score, and the number of acute relapses.
Reduced Fatigue and Relapses
The investigators found no significant differences at baseline between the study groups with respect to age, gender distribution, age of disease onset, EDSS score, and duration of fatigue. The level of fatigue was high at baseline; mean FIS score was 80 in the treatment group and 78 among controls, “suggesting that the patients had significant fatigue that affected their lives,” said Dr. Achiron. At six months, the relative FIS score decreased for all study participants. Only patients who received alfacalcidol, however, had a decrease in FIS score of at least 30%. FIS score was reduced by a mean of 41.6% among alfacalcidol-treated patients. The reduction was most noticeable on the cognitive subscale of FIS, compared with the physical and social subscales, said Dr. Achiron.
RAYS quality of life score improved at six months for patients treated with alfacalcidol. Physical quality of life did not change, but psychologic and social quality of life improved significantly in patients who received alfacalcidol. EDSS score did not change for any participants.
In addition, the number of relapses was significantly lower among participants receiving alfacalcidol, and the percentage of relapse-free patients was higher in the treatment group than in the control group. The difference between groups in the number of relapses was already evident at four months. The association between alfacalcidol and a reduction in relapses is consistent with literature suggesting that vitamin D enhances the apoptosis of autoreactive T cells, said Dr. Achiron.
“Alfacalcidol is a safe and effective treatment strategy for treating fatigue in MS,” she concluded.
—Erik Greb