Derfuss Tobias, Ontaneda Daniel, Nicholas Jacqueline, Meng Xiangyi, Hawker Kathleen
Departments of Neurology and Biomedicine, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland.
Mellen Center, Department of Neurology, Cleveland Clinic, Cleveland, OH, USA.
Mult Scler Relat Disord. 2016 Jul;8:124-30. doi: 10.1016/j.msard.2016.05.015. Epub 2016 May 24.
Fingolimod is a once-daily, orally administered therapy for relapsing forms of MS. It has been shown to reduce relapse rates significantly in all phase II and phase III clinical trials when compared with placebo and intramuscular interferon β-1a (IFNβ-1a IM).
This study compared annualized relapse rates (ARRs) associated with fingolimod, placebo and IFNβ-1a IM, in patient subgroups from the pooled FREEDOMS, FREEDOMS II, and TRANSFORMS populations. This provided a large data set in which the efficacy of fingolimod could be assessed across a range of patient subgroups, including clinically relevant subgroups not previously analysed.
Compared with placebo, fingolimod was associated with significantly lower ARRs across all patient subgroups with relative reductions in ARRs ranging from 35% (patients who had previously received treatment for their MS for up to 1 year; P<0.05) to 69% (patients with symptoms for less than 3 years before study entry; P<0.001). Other relative reductions in ARR compared with placebo included 64% in patients aged 40 years or younger and 63% in those naïve to treatment (P<0.001 for both). Compared with IFNβ-1a IM, the greatest benefits to ARR were seen in patients aged 40 years or younger (55% relative ARR reduction, P<0.001) and in a small subgroup of patients who had previously received IFNβ and glatiramer acetate (55% relative ARR reduction; P<0.05). Reductions in ARR compared with IFNβ-1a IM were not statistically significant in men (33%, P=0.081), in patients aged over 40 years (23%, P=0.230) and in those who had received treatment prior to the study for 1 year or less (35%, P=0.108). Fingolimod was associated with significantly lower ARRs compared with placebo and with IFNβ-1a IM irrespective of treatment status (treatment-naïve and previously treated for MS), and regardless of type of previous therapy.
Fingolimod provided consistent efficacy benefits over placebo and IFNβ-1a IM across a range of subgroups of patients with relapsing MS. The magnitude of the beneficial effect of fingolimod over IFNβ-1a IM may depend on age, sex, and duration of previous treatment. These findings suggest that most benefit will be gained by patients who start fingolimod early in the disease course, but the findings also suggest that fingolimod treatment will benefit patients later in the disease course when they have already accrued disability.
芬戈莫德是一种用于复发型多发性硬化症（MS）的每日一次口服疗法。与安慰剂和肌肉注射干扰素β-1a（IFNβ-1a IM）相比，在所有II期和III期临床试验中，它已显示出能显著降低复发率。
本研究比较了来自汇总的FREEDOMS、FREEDOMS II和TRANSFORMS人群的患者亚组中与芬戈莫德、安慰剂和IFNβ-1a IM相关的年化复发率（ARR）。这提供了一个大数据集，可在一系列患者亚组中评估芬戈莫德的疗效，包括先前未分析的临床相关亚组。
与安慰剂相比，芬戈莫德在所有患者亚组中的ARR均显著更低，ARR的相对降低幅度从35%（先前接受MS治疗长达1年的患者；P<0.05）到69%（研究入组前症状出现少于3年的患者；P<0.001）。与安慰剂相比，其他ARR的相对降低包括40岁及以下患者降低64%，未接受过治疗的患者降低63%（两者P<0.001）。与IFNβ-1a IM相比，在40岁及以下患者（ARR相对降低55%，P<0.001）以及一小部分先前接受过IFN和醋酸格拉替雷治疗的患者（ARR相对降低55%；P<0.05）中，ARR降低最为显著。与IFNβ-1a IM相比，男性（33%，P=0.081）、40岁以上患者（23%，P=0.230）以及研究前接受治疗1年或更短时间的患者（35%，P=0.108）的ARR降低无统计学意义。无论治疗状态（未接受过治疗和先前接受过MS治疗）以及先前治疗类型如何，与安慰剂和IFNβ-1a IM相比，芬戈莫德的ARR均显著更低。
在复发型MS患者的一系列亚组中，芬戈莫德相对于安慰剂和IFNβ-1a IM具有一致的疗效益处。芬戈莫德相对于IFNβ-1a IM的有益效果大小可能取决于年龄、性别和先前治疗持续时间。这些发现表明，在疾病病程早期开始使用芬戈莫德的患者将获得最大益处，但这些发现也表明，当患者已经出现残疾时，在疾病病程后期使用芬戈莫德治疗仍将使患者受益。
