Department of Neurology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Clinical Investigation, Kumamoto University Hospital, Kumamoto, Japan.
Sci Rep. 2018 Nov 6;8(1):16430. doi: 10.1038/s41598-018-34797-7.
Here, we determined whether degree of decreased heart rate due to fingolimod treatment correlates with decreasing degree of lymphocytes in relapse-remitting multiple sclerosis (RRMS). In total, 30 patients with RRMS were treated with 0.5 mg fingolimod and their heart rate recorded every 30 minutes for 24 hours. Time trends of heart rate were characterised as three individual amplitudes and phase angles from three cosine curves using a mixed-effect model. Spearman's correlation coefficient and regression analysis were used to determine the effect of heart rate information on change in lymphocyte count pre- and post-fingolimod treatment. Moreover, the degree of decreased lymphocytes induced by fingolimod treatment on heart rate was compared between low and high influence groups. Positive correlation between amplitude from the second curve and difference in lymphocyte number (p = 0.006) was observed. Regression analysis was also significant (p = 0.002). Moreover, the second curve derived from the high amplitude group exhibited a greater decrease in lymphocyte number after fingolimod treatment than the low amplitude group (p < 0.001). We suggest that the degree of decreased lymphocytes after fingolimod treatment (main effect) may be predicted by estimating the influence of degree in heart rate (side effect).
在这里，我们确定了由于 fingolimod 治疗导致的心率降低程度是否与复发缓解型多发性硬化症 (RRMS) 中淋巴细胞降低程度相关。共有 30 名 RRMS 患者接受了 0.5mg fingolimod 治疗，并在 24 小时内每 30 分钟记录一次心率。使用混合效应模型，通过三个余弦曲线将心率的时间趋势描述为三个个体幅度和相位角。使用 Spearman 相关系数和回归分析来确定心率信息对 fingolimod 治疗前后淋巴细胞计数变化的影响。此外，还比较了 fingolimod 治疗对心率降低的淋巴细胞诱导程度在低影响组和高影响组之间的差异。观察到第二曲线的幅度与淋巴细胞数量差异之间存在正相关（p=0.006）。回归分析也具有显著性（p=0.002）。此外，高幅度组的第二曲线在 fingolimod 治疗后显示出比低幅度组更大的淋巴细胞数量减少（p<0.001）。我们建议，通过估计心率（副作用）降低程度的影响，可以预测 fingolimod 治疗后淋巴细胞降低的程度（主要作用）。
