Ramos-Lopes Joana, Batista Sónia, Barradas Pedro, Campelo Isabel, Correia Inês, Nunes Carla, Macário Carmo, Sousa Lívia
Department of Neurology, Centro Hospitalar e Universitário de Coimbra, Praceta Professor Mota Pinto, 3000-075, Coimbra, Portugal.
Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Neurol Sci. 2021 Mar;42(3):1039-1043. doi: 10.1007/s10072-020-04629-6. Epub 2020 Jul 28.
Fingolimod is an oral daily treatment for relapsing remitting multiple sclerosis (RRMS). A decrease in lymphocytes count is a common side effect, whereby clinicians occasionally propose a reduced dose rather than its discontinuation. However, current data on the effectiveness of these regimens are scarce and contradictory. Our objective was to investigate if the fingolimod effectiveness is maintained with reduction in dosing frequency.
Retrospective and observational study of RRMS patients taking fingolimod-nondaily (FTY-ND) for at least 6 months. Propensity score-based matching was performed to select patients taking daily dose (FTY-ED) with comparable baseline characteristics: age, sex, disease duration, annualized relapse rate (ARR), and expanded disability status scale (EDSS). Afterwards, clinical and laboratorial assessment was evaluated in both groups.
Thirty-six patients were included in each group (FTY-ED vs. FTY-ND). Decrease in lymphocytes count was the main reason for switching to FTY-ND (88.9%). Previous treatment with natalizumab was inversely associated with risk of reducing dose (OR 0.253, 95%CI = 0.08-0.807, p = 0.016). There were no significant differences in clinical disease activity between patients FTY-ED vs. FTY-ND: mean ARR 0.4 vs. 0.3 (p = 0.247), median EDSS 2.0 vs. 2.0 (p = 0.687), and proportion of patients with EDSS increase 8.3% vs. 13.9% (p = 0.453). FTY-ND was overall well tolerated and was associated with an increase in the mean lymphocytes count (362 ± 103 cells/mm to 541 ± 183 cells/mm, p < 0.001).
These data suggest that the effectiveness of FTY is maintained despite the reduction of the dose, minimizing the most common adverse events. These findings warrant further confirmation, ideally with randomized clinical trials.
芬戈莫德是一种用于复发缓解型多发性硬化症（RRMS）的每日口服治疗药物。淋巴细胞计数减少是一种常见的副作用，临床医生偶尔会建议减少剂量而非停药。然而，目前关于这些治疗方案有效性的数据稀少且相互矛盾。我们的目的是研究芬戈莫德的有效性在给药频率降低时是否能维持。
对服用非每日剂量芬戈莫德（FTY-ND）至少6个月的RRMS患者进行回顾性观察研究。采用基于倾向评分的匹配方法选择具有可比基线特征的每日剂量服用者（FTY-ED）：年龄、性别、病程、年化复发率（ARR）和扩展残疾状态量表（EDSS）。之后，对两组患者进行临床和实验室评估。
每组纳入36例患者（FTY-ED与FTY-ND）。淋巴细胞计数减少是转为FTY-ND治疗的主要原因（88.9%）。既往使用那他珠单抗治疗与降低剂量的风险呈负相关（OR 0.253，95%CI = 0.08 - 0.807，p = 0.016）。FTY-ED组与FTY-ND组患者的临床疾病活动度无显著差异：平均ARR分别为0.4和0.3（p = 0.247），EDSS中位数分别为2.0和2.0（p = 0.687），EDSS升高的患者比例分别为8.3%和13.9%（p = 0.453）。FTY-ND总体耐受性良好，且与平均淋巴细胞计数增加有关（从362±103个细胞/mm³增至541±183个细胞/mm³，p < 0.001）。
这些数据表明，尽管剂量降低，FTY的有效性仍能维持，同时将最常见的不良事件降至最低。这些发现有待进一步证实，理想情况下需通过随机临床试验进行。
