BACKGROUND Fingolimod (FTY) is an effective second-line drug for relapsing-remitting multiple sclerosis, with ~50% patients showing no evidence of disease activity (NEDA) after 2 years. Nonetheless, the early identification of non-responders is extremely important, to promptly address them to more aggressive drugs. OBJECTIVES This cohort study evaluates FTY medium-term effectiveness, searching for early markers of treatment failure. PATIENTS AND METHODS Three hundred eighty patients starting FTY were enrolled and classified according to NEDA and time to first relapse criteria at 4-year follow-up. Logistic and Cox regression analyses were applied to identify early predictors of non-response. RESULTS At 4 years, 65.6% of patients were free from relapses and 35.4% had NEDA. Female gender was associated with a higher risk of non-response. Moreover, evidence of clinical and/or magnetic resonance imaging (MRI) activity during the first year of treatment was highly predictive of disease activity in the follow-up: the positive predictive value for non-response was 0.74 for the presence of ⩾1 relapse, 0.73 for the presence of ⩾1 active MRI lesion, and 0.83 for the presence of both clinical and MRI activity. CONCLUSIONS FTY effectiveness persists at medium-term follow-up; a close monitoring during the first year of treatment is warranted to early identify non-responders requiring treatment optimization.

中文翻译：

---

芬戈莫德期间疾病活动的早期证据预测复发缓解型多发性硬化症中期无效

背景 芬戈莫德 (FTY) 是一种治疗复发缓解型多发性硬化症的有效二线药物，约 50% 的患者在 2 年后没有表现出疾病活动性 (NEDA) 的证据。尽管如此，早期识别无反应者是非常重要的，以便及时解决他们使用更具攻击性的药物问题。目标 本队列研究评估 FTY 中期有效性，寻找治疗失败的早期标志物。患者和方法 入组 380 名开始 FTY 的患者，并根据 NEDA 和 4 年随访时的首次复发时间标准进行分类。Logistic 和 Cox 回归分析用于确定无反应的早期预测因素。结果 4 年时，65.6% 的患者没有复发，35.4% 的患者患有 NEDA。女性与更高的无反应风险相关。而且，第一年治疗期间临床和/或磁共振成像 (MRI) 活动的证据对随访中的疾病活动具有高度预测性：对于存在 ⩾1 复发的无反应阳性预测值为 0.74，0.73存在 ⩾1 个活动性 MRI 病变，0.83 表示存在临床和 MRI 活动。结论 FTY 有效性在中期随访中持续存在；有必要在治疗的第一年进行密切监测，以及早发现需要优化治疗的无反应者。和 0.83 的临床和 MRI 活动的存在。结论 FTY 有效性在中期随访中持续存在；有必要在治疗的第一年进行密切监测，以及早发现需要优化治疗的无反应者。和 0.83 的临床和 MRI 活动的存在。结论 FTY 的有效性在中期随访中持续存在；有必要在治疗的第一年进行密切监测，以及早发现需要优化治疗的无反应者。