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一种利用临床数据预测治疗多发性硬化症复发的最佳个体化糖皮质激素剂量的算法。

An algorithm using clinical data to predict the optimal individual glucocorticoid dosage to treat multiple sclerosis relapses.

作者信息

Gili-Kovács Judit, Hoepner Robert, Salmen Anke, Bagnoud Maud, Gold Ralf, Chan Andrew, Briner Myriam

机构信息

Department of Neurology, University Hospital Bern, Inselspital, Freiburgstrasse 18, Bern, 3010, Switzerland.

Department of Neurology, University Hospital Bern, Inselspital, Bern, Switzerland.

出版信息

Ther Adv Neurol Disord. 2021 Jun 17;14:17562864211020074. doi: 10.1177/17562864211020074. eCollection 2021.

Abstract

BACKGROUND

Glucocorticoid (GC) pulse therapy is used for multiple sclerosis (MS) relapse treatment; however, GC resistance is a common problem. Considering that GC dosing is individual with several response-influencing factors, establishing a predictive model, which supports clinicians to estimate the maximum GC dose above which no additional therapeutic value can be expected presents a huge clinical need.

METHOD

We established two, independent retrospective cohorts of MS patients. The first was an explorative cohort for model generation, while the second was established for its validation. Using the explorative cohort, a multivariate regression analysis with the GC dose used as the dependent variable and serum vitamin D (25D) concentration, sex, age, EDSS, contrast enhancement on cranial magnetic resonance imaging (MRI), immune therapy, and the involvement of the optic nerve as independent variables was established.

RESULTS

In the explorative cohort, 113 MS patients were included. 25-hydroxyvitamin D (25D) serum concentration and the presence of optic neuritis were independent predictors of the GC dose needed to treat MS relapses [(25D): -25.95 (95% confidence interval (CI)): -47.40 to -4.49;  = 0.018; optic neuritis: 2040.51 (95% CI: 584.64-3496.36),  = 0.006]. Validation of the multivariate linear regression model was performed within a second cohort. Here, the predicted GC dose did not differ significantly from the dose administered in clinical routine (mean difference: -843.54; 95% CI: -2078.08-391.00;  = 30,  = 0.173).

CONCLUSION

Our model could predict the GC dose given in clinical, routine MS relapse care, above which clinicians estimate no further benefit. Further studies should validate and improve our algorithm to help the implementation of predictive models in GC dosing.

摘要

背景

糖皮质激素(GC)脉冲疗法用于治疗多发性硬化症(MS)复发;然而,GC抵抗是一个常见问题。鉴于GC给药是个体化的,且有多个影响反应的因素,建立一个预测模型,以支持临床医生估计超过此剂量预期不会有额外治疗价值的最大GC剂量,具有巨大的临床需求。

方法

我们建立了两个独立的MS患者回顾性队列。第一个是用于模型生成的探索性队列,第二个是用于验证的队列。利用探索性队列,建立了以GC剂量为因变量,血清维生素D(25D)浓度、性别、年龄、扩展残疾状态量表(EDSS)、头颅磁共振成像(MRI)对比增强、免疫治疗以及视神经受累情况为自变量的多因素回归分析。

结果

在探索性队列中,纳入了113例MS患者。25-羟维生素D(25D)血清浓度和视神经炎的存在是治疗MS复发所需GC剂量的独立预测因素[(25D):-25.95(95%置信区间(CI)):-47.40至-4.49;P = 0.018;视神经炎:2040.51(95%CI:584.64 - 3496.36),P = 0.006] 在第二个队列中对多因素线性回归模型进行了验证。在此队列中,预测的GC剂量与临床常规给药剂量无显著差异(平均差异:-843.54;95%CI:-2078.08至391.00;P = 0.173,n = 30)。

结论

我们的模型可以预测临床常规MS复发治疗中给予的GC剂量,超过此剂量临床医生估计不会有进一步益处。进一步的研究应验证并改进我们的算法,以帮助在GC给药中实施预测模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/526f/8216377/3fc915b3b991/10.1177_17562864211020074-fig1.jpg

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