Aguila Lisbeth A, Pereira Rosa M R, Seguro Luciana P, Ugolini-Lopes Michelle R, Guedes Lissiane K N, Sales Lucas P, Fernandes Alan L, de Santana Felipe M, Caparbo Valéria F, Takayama Liliam, Borba Eduardo F, Domiciano Diogo S
Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, Av Dr Arnaldo, 455 - Reumatologia, 3O Andar, Sala 3193, Cerqueira César, São Paulo, Brazil.
Bone Mineral Metabolism Laboratory, Rheumatology Division, Faculdade de Medicina, Universidade de São Paulo, São Paulo, 01246-903, Brazil.
Clin Rheumatol. 2025 Aug 16. doi: 10.1007/s10067-025-07633-3.
INTRODUCTION/OBJECTIVES: This study evaluated high- vs. routine-dose vitamin D3 in severe SLE patients on high-dose glucocorticoids, an underrepresented group in research.
In a randomized, double-blind, placebo-controlled trial, 40 SLE inpatients receiving intravenous pulse methylprednisolone were assigned to "high-dose" (HD) (100,000 IU of vitamin D3 plus 7000 IU weekly, n = 20) or "routine-dose" (RD) vitamin D3 group (placebo plus 7000 IU weekly, n = 20) for 24 weeks. Changes in disease activity were assessed from baseline to study end.
Baseline SLEDAI scores were comparable between the HD group (median 19) and the RD group (median 14.5; p = 0.230). After 24 weeks, the HD group had a significantly greater increase in 25OHD concentrations (median 15.4 ng/ml) compared to the RD group (median 8.0 ng/ml; p = 0.028). No difference in SLEDAI scores was observed; however, there was a trend toward a greater ΔC4 increase in the HD group (7.38 vs. 3.27, p = 0.093). Δ25OHD showed positive correlations with disease activity markers. ROC analysis identified Δ25OHD cutoffs of 12.9 ng/ml (AUC = 0.741) for C3 and 11.7 ng/ml (AUC = 0.757) for C4 normalization, indicating that exceeding these may improve complement normalization.
Although SLEDAI scores did not differ between groups, high-dose vitamin D led to greater increases in 25OHD levels and showed trends toward improved serological markers. These exploratory findings suggest potential biological effects and support the safety and feasibility of high weekly doses (up to 100,000 IU), warranting further investigation in severe SLE.
引言/目的：本研究评估了高剂量与常规剂量维生素D3对接受高剂量糖皮质激素治疗的重症系统性红斑狼疮（SLE）患者的影响，这是一个在研究中未得到充分体现的群体。
在一项随机、双盲、安慰剂对照试验中，40名接受静脉注射甲泼尼龙冲击治疗的SLE住院患者被分为“高剂量”（HD）组（100,000国际单位维生素D3加每周7000国际单位，n = 20）或“常规剂量”（RD）维生素D3组（安慰剂加每周7000国际单位，n = 20），为期24周。评估从基线到研究结束时疾病活动度的变化。
HD组（中位数19）和RD组（中位数14.5；p = 0.230）的基线SLEDAI评分相当。24周后，HD组的25羟维生素D（25OHD）浓度升高幅度（中位数15.4纳克/毫升）显著大于RD组（中位数8.0纳克/毫升；p = 0.028）。未观察到SLEDAI评分有差异；然而，HD组C4升高幅度有更大的趋势（7.38对3.27，p = 0.093）。25OHD变化与疾病活动标志物呈正相关。ROC分析确定C3正常化时Δ25OHD的截断值为12.9纳克/毫升（AUC = 0.741），C4正常化时为11.7纳克/毫升（AUC = 0.757），表明超过这些值可能改善补体正常化。
尽管两组之间SLEDAI评分没有差异，但高剂量维生素D导致25OHD水平有更大升高，并显示出血清学标志物改善的趋势。这些探索性发现提示了潜在的生物学效应，并支持每周高剂量（高达100,000国际单位）的安全性和可行性，值得在重症SLE中进一步研究。
