在复发缓解型多发性硬化症青年成年患者中，立即与延迟使用芬戈莫德治疗的长期效果：来自FREEDOMS/FREEDOMS II试验的汇总分析
Long-Term Effect of Immediate Versus Delayed Fingolimod Treatment in Young Adult Patients with Relapsing-Remitting Multiple Sclerosis: Pooled Analysis from the FREEDOMS/FREEDOMS II Trials.
作者信息
Ghezzi Angelo, Chitnis Tanuja, K-Laflamme Annik, Meinert Rolf, Häring Dieter A, Pohl Daniela
机构信息
Centro Studi Sclerosi Multipla, Gallarate, Italy.
Partners Pediatric Multiple Sclerosis Centre, Massachusetts General Hospital, Boston, MA, USA.
出版信息
Neurol Ther. 2019 Dec;8(2):461-475. doi: 10.1007/s40120-019-0146-z. Epub 2019 Jul 19.
INTRODUCTION
Fingolimod has demonstrated clinical and MRI benefits versus placebo/interferon β-1a in young adults with multiple sclerosis (MS). Here we report the long-term effects of fingolimod 0.5 mg on clinical and MRI outcomes in young adults with MS aged ≤ 30 years followed up for up to 8 years (96 months).
METHODS
This post hoc analysis of pooled FREEDOMS/FREEDOMS II studies included patients who either received fingolimod 0.5 mg from randomization (immediate; N = 163) or switched from placebo to fingolimod at month (M) 24 (delayed; N = 147). The 6-month confirmed disability improvement [6m-CDI: based on Expanded Disability Status Scale (EDSS)], 6m-CDI-plus (6m-CDI+; EDSS, 9-Hole Peg Test, Timed 25-Foot Walk Test), 6-month confirmed disability progression (6m-CDP), time to EDSS score ≥ 4, annualized relapse rates (ARRs), new/newly enlarging T2 (neT2) lesions, and annual rate of brain volume loss (BVL) were analyzed from baseline to M24, M48, and M96. Cox regression and negative binomial regression models were used to analyze measured outcomes.
RESULTS
At baseline, more than two-thirds of young adult patients were treatment naïve, had more than two relapses in the previous 2 years, and EDSS score < 2. From M0 to M96, a significantly higher proportion of young adult patients in the immediate group (vs. delayed group) achieved 6m-CDI (58.2% vs. 30.5%, p = 0.0206) and 6m-CDI+ (70.6% vs. 42.3%, p = 0.0149); significantly fewer patients reached 6m-CDP (20.1% vs. 34.7%, p = 0.0058) and EDSS ≥ 4 (24.1% vs. 34.1%, p = 0.0041). Up to M96, young adults in the immediate versus delayed group had lower ARRs (0.16 vs. 0.38, p < 0.0001) and a higher proportion of patients were free of neT2 lesions at M48 (31.0% vs. 5.0%, p = 0.0011).
CONCLUSION
In young adult patients with MS, immediate versus delayed fingolimod treatment was associated with improved disease outcomes and greater long-term benefits in both disease activity and disability progression.
FUNDING
Novartis Pharma AG.
引言
在患有多发性硬化症（MS）的年轻成年人中，与安慰剂/干扰素β-1a相比，芬戈莫德已显示出临床和MRI方面的益处。在此，我们报告了0.5毫克芬戈莫德对年龄≤30岁的MS年轻成年人的临床和MRI结果的长期影响，随访时间长达8年（96个月）。
方法
这项对FREEDOMS/FREEDOMS II汇总研究的事后分析纳入了从随机分组开始接受0.5毫克芬戈莫德治疗的患者（立即治疗组；N = 163）或在第24个月从安慰剂转换为芬戈莫德的患者（延迟治疗组；N = 147）。分析了从基线到第24个月、第48个月和第96个月的6个月确认残疾改善情况[6个月确认残疾改善（6m-CDI）：基于扩展残疾状态量表（EDSS）]、6m-CDI加（6m-CDI+；EDSS、9孔插钉试验、定时25英尺步行试验）、6个月确认残疾进展（6m-CDP）、达到EDSS评分≥4的时间、年化复发率（ARR）、新的/新增大的T2（neT2）病灶以及脑容量损失年率（BVL）。使用Cox回归和负二项回归模型分析测量结果。
结果
在基线时，超过三分之二的年轻成年患者未接受过治疗，在过去2年中有超过两次复发，且EDSS评分<2。从第0个月到第96个月，立即治疗组（与延迟治疗组相比）中达到6m-CDI（58.2%对30.5%，p = 0.0206）和6m-CDI+（70.6%对42.3%，p = 0.0149）的年轻成年患者比例显著更高；达到6m-CDP（20.1%对34.7%，p = 0.0058）和EDSS≥4（24.1%对34.1%，p = 0.0041）的患者显著更少。直至第96个月，立即治疗组与延迟治疗组的年轻成年人ARR更低（0.16对0.38，p<0.0001），且在第48个月无neT2病灶的患者比例更高（31.0%对5.0%，p = 0.0011）。
结论
在患有MS的年轻成年患者中，与延迟使用芬戈莫德治疗相比，立即使用芬戈莫德治疗与疾病结果改善以及在疾病活动和残疾进展方面更大的长期益处相关。
资助
诺华制药公司。
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