Multiple Sclerosis Center, Sheba Medical Center, Tel-Hashomer, 52621, Israel
Multiple Sclerosis Center, Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Israel.
Mult Scler. 2015 May;21(6):767-75. doi: 10.1177/1352458514554053. Epub 2014 Oct 24.
Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS); however, there is no medication that has been approved specifically to treat MS-related fatigue.
We aimed to evaluate the effect of vitamin D analogue, Alfacalcidol, on MS-related fatigue.
DESIGN, SETTINGS, PARTICIPANTS: This was a randomized, double-blind, parallel group, placebo-controlled trial in patients with clinically definite MS by McDonald criteria conducted in a single university-affiliated medical center in Israel. Randomly selected patients from the Sheba MS Registry computerized database (N=600) were assessed using the self-report Fatigue Severity Scale (FSS). Patients with clinically meaningful fatigue (N=259) were further assessed for trial eligibility, and MS patients with significant fatigue (N=158; 61%, 118 females, mean age 41.1 ± 9.2 years and mean disease duration of 6.2 ± 5.5 years) were included in the study and randomized to receive treatment or placebo.
Alfacalcidol (1 mcg/d, N=80) or placebo (N=78) was administered for six consecutive months.
The primary endpoint of the study was the change between Alfacalcidol and placebo-treated patients in the Fatigue Impact Scale (FIS) score; the cut-off point for improvement was defined as 30% decrease. All analyses followed the intention-to-treat principle and were performed for all participants based on the group they were randomly allocated regardless of whether or not they dropped out.
Alfacalcidol decreased the mean relative FIS score as compared with placebo (-41.6% vs. -27.4%, p=0.007, respectively). This advantage was further emphasized when the modified FIS (MFIS) relative change was calculated. Quality of Life (QoL) improved in Alfacalcidol-treated patients as compared with placebo in the RAYS psychological (p=0.033) and social (p=0.043) sub-scales. The Alfacalcidol-treated group had reduced number of relapses (p=0.006) and higher proportion of relapse-free patients (p=0.007). Reduction of relapses by Alfacalcidol became significant at 4 months of treatment, was sustained at 6 months and decayed 2 months after drug discontinuation. Alfacalcidol treatment was safe and no serious adverse events were recorded.
Alfacalcidol is a safe and effective treatment strategy to decrease fatigue and improve QoL in patients with MS.
疲劳是多发性硬化症（MS）最常见和最具致残性的症状之一；然而，目前尚无专门用于治疗 MS 相关性疲劳的药物。
我们旨在评估维生素 D 类似物，阿尔法骨化醇，对 MS 相关性疲劳的影响。
设计、设置、参与者：这是一项在以色列的一家大学附属医院进行的、按麦克唐纳标准确诊的临床 MS 患者的随机、双盲、平行组、安慰剂对照试验。从希巴 MS 注册数据库的计算机化数据库中随机选择患者（N=600），使用自我报告疲劳严重程度量表（FSS）进行评估。具有临床意义的疲劳患者（N=259）进一步评估是否符合试验条件，MS 伴明显疲劳的患者（N=158；61%，118 名女性，平均年龄 41.1±9.2 岁，平均病程 6.2±5.5 年）纳入研究并随机接受治疗或安慰剂。
阿尔法骨化醇（1 mcg/d，N=80）或安慰剂（N=78）连续治疗 6 个月。
研究的主要终点是接受阿尔法骨化醇和安慰剂治疗的患者在疲劳影响量表（FIS）评分上的变化；改善的截断点定义为 30%的下降。所有分析均遵循意向治疗原则，并根据患者随机分组进行，无论其是否脱落，均基于其分组进行分析。
与安慰剂相比，阿尔法骨化醇降低了平均相对 FIS 评分（-41.6%与-27.4%，p=0.007）。当计算改良 FIS（MFIS）相对变化时，这种优势更加明显。与安慰剂相比，阿尔法骨化醇治疗患者的生活质量（QoL）在 RAYS 心理（p=0.033）和社会（p=0.043）亚量表中得到改善。阿尔法骨化醇治疗组的复发次数减少（p=0.006），无复发患者的比例增加（p=0.007）。阿尔法骨化醇治疗的缓解作用在治疗 4 个月时变得显著，在治疗 6 个月时持续，并在停药后 2 个月时减弱。阿尔法骨化醇治疗安全，无严重不良事件记录。
阿尔法骨化醇是一种安全有效的治疗策略，可降低 MS 患者的疲劳感并改善其生活质量。
