RRMS 患者皮下注射干扰素 β-1a 时每日高剂量维生素 D 的随机试验。
Randomized trial of daily high-dose vitamin D in patients with RRMS receiving subcutaneous interferon β-1a.
机构信息
From the Department of Neurology (R.H., J.S.,), Zuyderland Medical Centre Sittard, Maastricht University Medical Centre; Department of Neurology (J.S.), Canisius Wilhelmina Ziekenhuis, Nijmegen, the Netherlands; Department of Nutritional Sciences (R.V.), University of Toronto, Canada; Akershus University Hospital and University of Oslo (T.H.), Norway; Merck GmbH (K.M.), Vienna, Austria; Service de Neurologie (M.S.), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; Departments of Neurology (J.K.) and Radiology and Nuclear Medicine (F.B.), VU University Medical Centre, Amsterdam, the Netherlands; Institutes of Neurology and Healthcare Engineering (F.B.), University College London, UK; Independent Consultant (M.B.), Krailling, Germany; and U.O.C. Neurologia and Multiple Sclerosis Center (L.M.E.G.), Fondazione Istituto G. Giglio di Cefalù, Italy.
出版信息
Neurology. 2019 Nov 12;93(20):e1906-e1916. doi: 10.1212/WNL.0000000000008445. Epub 2019 Oct 8.
OBJECTIVE
In the phase II, randomized, double-blind, placebo-controlled Supplementation of Vigantol Oil versus Placebo Add-on in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Receiving Rebif Treatment (SOLAR) study (NCT01285401), we assessed the efficacy and safety of add-on vitamin D in patients with RRMS.
METHODS
Eligible patients with RRMS treated with SC interferon-β-1a (IFN-β-1a) 44 μg 3 times weekly and serum 25(OH)D levels <150 nmol/L were included. From February 15, 2011, to May 11, 2015, 229 patients were included and randomized 1:1 to receive SC IFN-β-1a plus placebo (n = 116) or SC IFN-β-1a plus oral high-dose vitamin D 14,007 IU/d (n = 113). The revised primary outcome was the proportion of patients with no evidence of disease activity (NEDA-3) at week 48.
RESULTS
At 48 weeks, 36.3% of patients who received high-dose vitamin D had NEDA-3, without a statistically significant difference in NEDA-3 status between groups (placebo 35.3%; odds ratio 0.93; 95% confidence interval [CI] 0.53-1.63; = 0.80). Compared with placebo, the high-dose vitamin D group had better MRI outcomes for combined unique active lesions (incidence rate ratio 0.68; 95% CI 0.52-0.89; = 0.0045) and change from baseline in total volume of T2 lesions (difference in mean ranks: -0.074; = 0.035).
CONCLUSIONS
SOLAR did not establish a benefit for high-dose vitamin D as add-on to IFN-β-1a, based on the primary outcome of NEDA-3, but findings from exploratory outcomes suggest protective effects on development of new MRI lesions in patients with RRMS.
CLINICALTRIALSGOV IDENTIFIER
NCT01285401.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that for patients with RRMS treated with SC IFN-β-1a, 48 weeks of cholecalciferol supplementation did not promote NEDA-3 status.
目的
在接受 Rebif 治疗的复发性缓解型多发性硬化症（RRMS）患者中，评估添加维生素 D 对疾病的疗效和安全性。方法：纳入 RRMS 患者，每周皮下注射干扰素-β-1a（IFN-β-1a）44μg 3 次，血清 25(OH)D 水平<150nmol/L。2011 年 2 月 15 日至 2015 年 5 月 11 日，共纳入 229 例患者，并按 1:1 随机分为皮下注射 IFN-β-1a 联合安慰剂（n=116）或皮下注射 IFN-β-1a 联合口服高剂量维生素 D 14007IU/d（n=113）。修订后的主要终点是第 48 周无疾病活动证据（NEDA-3）的患者比例。结果：48 周时，接受高剂量维生素 D 的患者中有 36.3%达到 NEDA-3，组间 NEDA-3 状态无统计学差异（安慰剂组为 35.3%；比值比 0.93；95%置信区间 [CI]0.53-1.63；=0.80）。与安慰剂相比，高剂量维生素 D 组联合独特活跃病变的 MRI 结果更好（发生率比 0.68；95%CI0.52-0.89；=0.0045），从基线到 T2 病变总体积的变化（平均秩差异：-0.074；=0.035）。结论：基于 NEDA-3 的主要结局，SOLAR 并未确定高剂量维生素 D 作为 IFN-β-1a 的附加治疗对多发性硬化症患者的益处，但探索性结局的结果表明，高剂量维生素 D 对 RRMS 患者新 MRI 病变的发展具有保护作用。临床试验.gov 标识符：NCT01285401。证据分类：本研究提供 II 级证据，表明对于接受皮下注射 IFN-β-1a 治疗的 RRMS 患者，48 周的胆钙化醇补充剂并未促进 NEDA-3 状态。
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