Vermersch Patrick, Radue Ernst-Wilhelm, Putzki Norman, Ritter Shannon, Merschhemke Martin, Freedman Mark S
University of Lille, CHU Lille, LIRIC - INSERM U995, FHU Imminent, France.
Medical Image Analysis Center, University Hospital Basel, Switzerland.
Mult Scler J Exp Transl Clin. 2017 Sep 27;3(3):2055217317730096. doi: 10.1177/2055217317730096. eCollection 2017 Jul-Sep.
Cases of higher-than-expected disease activity have been reported following fingolimod discontinuation.
The objective of this paper is to assess the risk of substantially higher-than-expected disease activity post-study drug discontinuation (SDD) at the individual patient level using data from the Phase III, placebo-controlled FREEDOMS and FREEDOMS II trials.
Baseline gadolinium-enhancing T1-lesion volumes were used to statistically model the expected level of MRI disease activity post-SDD. Patients exceeding this level were classed as "MRI outliers." Patients with an unusually high increase in Expanded Disability Status Scale score, hospitalization for relapse, severe relapse, or relapse with incomplete recovery post-SDD were classed as "clinical outliers."
In FREEDOMS, the number of MRI outliers post-SDD was 2/69 (2.9%), 1/65 (1.5%) and 7/83 (8.4%) for the placebo, fingolimod 0.5 mg, and fingolimod 1.25 mg groups, respectively. In FREEDOMS II, the corresponding numbers were 4/72 (5.6%), 6/79 (7.6%) and 3/73 (4.1%). The number of clinical outliers across both trials was low. No consistent evidence of placebo vs fingolimod, dose-related or inter-trial patterns was discernable.
The low number of clinical and MRI outliers and lack of any discernible pattern within and between trials, including between placebo and fingolimod, argues against a systematic risk of higher-than-expected recurrence of disease activity following discontinuation of fingolimod.
据报道，停用芬戈莫德后疾病活动高于预期的病例。
本文的目的是使用III期、安慰剂对照的FREEDOMS和FREEDOMS II试验的数据，在个体患者层面评估研究药物停药（SDD）后疾病活动显著高于预期的风险。
使用基线钆增强T1病变体积对SDD后MRI疾病活动的预期水平进行统计建模。超过该水平的患者被归类为“MRI异常值”。SDD后扩展残疾状态量表评分异常增加、因复发住院、严重复发或复发后恢复不完全的患者被归类为“临床异常值”。
在FREEDOMS中，安慰剂组、芬戈莫德0.5mg组和芬戈莫德1.25mg组SDD后MRI异常值的数量分别为2/69（2.9%）、1/65（1.5%）和7/83（8.4%）。在FREEDOMS II中，相应的数字分别为4/72（5.6%）、6/79（7.6%）和3/73（4.1%）。两项试验中临床异常值的数量都很低。未发现安慰剂与芬戈莫德、剂量相关或试验间模式的一致证据。
临床和MRI异常值数量少，且试验内和试验间（包括安慰剂和芬戈莫德之间）没有任何可辨别的模式，这表明停用芬戈莫德后疾病活动高于预期复发的系统性风险并不存在。
