Neuroimmunology Unit, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Clin Immunol. 2010 Oct;137(1):15-20. doi: 10.1016/j.clim.2010.06.005.
FTY720 (Fingolimod) reduces multiple sclerosis disease activity by inducing lymphopenia and inhibiting lymphocyte re-entry from lymph nodes. Peripheral lymphocyte reconstitution following drug discontinuation has been considered relatively rapid (2-4 weeks), based on short-term studies. We investigated the kinetics of lymphocyte reconstitution in MS patients in open label extension phases of FTY720 clinical trials who discontinued therapy after prolonged use (>1-5 years), and examined histological features of a mediastinal lymph node obtained from a lymphopenic FTY720 patient. Although three patients showed reconstitution of peripheral lymphocytes within the predicted timeline, two patients continued to be lymphopenic 9 and 34 months after therapy cessation. Lymph nodes from the latter patient showed preserved architecture. Notwithstanding preserved lymph node integrity, time for lymphocyte reconstitution after prolonged FTY720 therapy can be significantly greater than predicted by shorter-term studies. This is relevant for clinical decisions regarding management of patients using this therapy and for introducing alternate therapies.
富马酸二甲酯（FTY720）通过诱导淋巴细胞减少和抑制淋巴细胞从淋巴结重新进入来减少多发性硬化症的疾病活动。基于短期研究，停药后外周淋巴细胞重建被认为相对较快（2-4 周）。我们在 FTY720 临床试验的开放标签扩展阶段调查了长期使用（>1-5 年）后停止治疗的 MS 患者淋巴细胞重建的动力学，并检查了从淋巴细胞减少的 FTY720 患者纵隔淋巴结获得的组织学特征。尽管有三名患者在预测的时间范围内重建了外周淋巴细胞，但有两名患者在停药后 9 个月和 34 个月仍持续淋巴细胞减少。来自后者的淋巴结显示出保存的结构。尽管淋巴结完整性得以保存，但 FTY720 治疗后淋巴细胞重建的时间可能明显长于短期研究预测的时间。这与使用这种疗法的患者的管理和引入替代疗法的临床决策有关。
