Manon Rival研究组报道了高剂量维生素D治疗多发性硬化症临床孤立综合征。2025年3月10日出版的《美国医学会杂志》发表了这项成果。

重要性:维生素D缺乏是多发性硬化症（MS）的一个危险因素，与疾病活动的风险相关，但关于补充维生素D的益处的数据是相互矛盾的。

目的:评价高剂量胆骨化醇单药治疗多发性硬化症（ms）典型临床孤立综合征（CIS）患者降低疾病活动性的疗效

设计、设置和参与者：D-Lay MS试验是一项平行、双盲、随机、安慰剂对照的临床试验，在法国的36个MS中心进行。患者入组时间为2013年7月至2020年12月（最终随访时间为2023年1月18日）。招募年龄在18 - 55岁、CIS持续时间小于90天、血清维生素D浓度小于100nmol/L、磁共振诊断成像（MRI）符合2010年空间扩散或2个或更多病变和存在寡克隆带的标准的CIS患者。

干预措施 ；患者按1:1随机分组接受口服胆钙化醇100每2周000 IU （n = 163）或安慰剂（n = 153），持续24个月。

主要成果和措施：主要结局指标是疾病活动性，定义为24个月随访期间的复发和/或MRI活动性（新发和/或增强病变），也作为单独的次要结局进行分析。

结果:在纳入并随机分配的316名参与者中(中位[IQR]年龄34[28-42]岁；主要分析包括303例（95.9%）患者至少服用了1剂研究药物，288例（91.1%）最终完成了24个月的试验。维生素D组94例（60.3%）患者出现疾病活动，安慰剂组109例（74.1%）患者出现疾病活动(风险比[HR]， 0.66；P = 0.004)，维生素D组到疾病活动的中位时间更长(432天vs 224天；log-rank P = .003)。所有3个次要MRI结果均报告了维生素D组与安慰剂组的显著差异：MRI活性(89例[57.1%]对96例[65.3%]；Hr, 0.71；P =.02)，新发病变(72例[46.2%]vs 87例[59.2%]；Hr, 0.61；P = 0.003)，对比增强病变(29例[18.6%]vs 50例[34.0%]；Hr, 0.47；P = 措施)。所有10项次要临床结果均无显著差异，包括复发，维生素D组有28例患者（17.9%）复发，安慰剂组有32例患者（21.8%）复发(HR, 0.69；P = 。16)。在247名患者的亚组中，在治疗开始时符合2017年更新的复发-缓解型MS诊断标准，结果相似。维生素D组和安慰剂组分别有17例和13例患者发生了严重的不良事件，这些不良事件均与胆钙化醇无关。

研究结果表明，口服胆钙化醇100每2周000 IU显著降低CIS和早期复发缓解型MS的疾病活动性。这些结果值得进一步研究，包括脉冲高剂量维生素D作为附加治疗的潜在作用。

附：英文原文

Title: High-Dose Vitamin D in Clinically Isolated Syndrome Typical of Multiple Sclerosis: The D-Lay MS Randomized Clinical Trial

Author: Eric Thouvenot, David Laplaud, Christine Lebrun-Frenay, Nathalie Derache, Emmanuelle Le Page, Elisabeth Maillart, Caroline Froment-Tilikete, Giovanni Castelnovo, Olivier Casez, Marc Coustans, Anne-Marie Guennoc, Olivier Heinzlef, Laurent Magy, Chantal Nifle, Xavier Ayrignac, Agnès Fromont, Nicolas Gaillard, Nathalie Caucheteux, Ivania Patry, Jérme De Sèze, Romain Deschamps, Pierre Clavelou, Damien Biotti, Gilles Edan, William Camu, Hanane Agherbi, Dimitri Renard, Christophe Demattei, Pascale Fabbro-Peray, Thibault Mura, Manon Rival, D-Lay MS Investigators, Frédéric TAITHE, Dominique AUFAUVRE, Thibault MOREAU, Mathieu VAILLANT, Olivier OUTTERYCK, Gauthier CALAIS, Patrick HAUTECOEUR, Alexis MONTCUQUET, Clarisse CARRA DALLIERE, Sophie PITTION-VOUYOVITCH, Caroline LANCIN GARCIA, Laure MICHEL, Mirela FAIGHEL, Aurelia SCHUNCK, Sandrine WIERTLEWSKI, Violaine TALMANT, Flora LEJEUNE, Loreen DELALANDE, Laura COULOUME, Mickael COHEN, Anne WACONGNE, Julie MAS, Adil MAAROUF, Ayman TOURBAH, Véronique DEBURGHGRAEVE, Anne KERBAT, Bertrand BOURRE, David BRASSAT, Jonathan CIRON, Julien BIBERON, Richard DEVY, Jennifer YEUNG, Olivier GOUT, Aurélien BENOILID, Nicolas COLLONGUES, Céline LOUAPRE, Aurelian UNGUREANU, Caroline PAPEIX, Laure DUBESSY Anne, Damien GALANAUD, Sandra VUKUSIC, Franoise DURAND-DUBIEF

Issue&Volume: 2025-03-10

Abstract: Importance  Vitamin D deficiency is a risk factor for multiple sclerosis (MS) and is associated with the risk of disease activity, but data on the benefits of supplementation are conflicting.

Objective  To evaluate the efficacy of high-dose cholecalciferol as monotherapy in reducing disease activity in patients with clinically isolated syndrome (CIS) typical for MS.

Design, Setting, and Participants  The D-Lay MS trial was a parallel, double-blind, randomized placebo-controlled clinical trial in 36 MS centers in France. Patients were enrolled from July 2013 to December 2020 (final follow-up on January 18, 2023). Untreated patients with CIS aged 18 to 55 years with CIS duration less than 90 days, serum vitamin D concentration less than 100 nmol/L, and diagnostic magnetic resonance imaging (MRI) meeting 2010 criteria for dissemination in space or 2 or more lesions and presence of oligoclonal bands were recruited.

Intervention  Patients were randomized 1:1 to receive oral cholecalciferol 100000 IU (n=163) or placebo (n=153) every 2 weeks for 24 months.

Main Outcomes and Measures  The primary outcome measure was disease activity, defined as occurrence of a relapse and/or MRI activity (new and/or contrast-enhancing lesions) over 24 months of follow-up, also analyzed as separate secondary outcomes.

Results  Of the 316 participants enrolled and randomized (median [IQR] age, 34 [28-42] years; 70% women), the primary analysis included 303 patients (95.9%) who took at least 1 dose of the study drug and 288 (91.1%) ultimately completed the 24-month trial. Disease activity was observed in 94 patients (60.3%) in the vitamin D group and 109 patients (74.1%) in the placebo group (hazard ratio [HR], 0.66 [95% CI, 0.50-0.87]; P=.004), and median time to disease activity was longer in the vitamin D group (432 vs 224 days; log-rank P=.003). All 3 secondary MRI outcomes reported significant differences favoring the vitamin D group vs the placebo group: MRI activity (89 patients [57.1%] vs 96 patients [65.3%]; HR, 0.71 [95% CI, 0.53-0.95]; P=.02), new lesions (72 patients [46.2%] vs 87 patients [59.2%]; HR, 0.61 [95% CI, 0.44-0.84]; P=.003), and contrast-enhancing lesions (29 patients [18.6%] vs 50 patients [34.0%]; HR, 0.47 [95% CI, 0.30-0.75]; P=.001). All 10 secondary clinical outcomes showed no significant difference, including relapse, which occurred in 28 patients (17.9%) in the vitamin D group vs 32 (21.8%) in the placebo group (HR, 0.69 [95% CI, 0.42-1.16]; P=.16). Results were similar in a subset of 247 patients meeting updated 2017 diagnostic criteria for relapsing-remitting MS at treatment initiation. Severe adverse events occurred in 17 patients in the vitamin D group and 13 in the placebo group, none of which were related to cholecalciferol.

Conclusions and Relevance  Oral cholecalciferol 100000 IU every 2 weeks significantly reduced disease activity in CIS and early relapsing-remitting MS. These results warrant further investigation, including the potential role of pulse high-dose vitamin D as add-on therapy.

DOI: 10.1001/jama.2025.1604

Source: https://jamanetwork.com/journals/jama/fullarticle/2831270