奥扎莫德对复发型多发性硬化症符号数字模式测验表现的影响。
Effect of Ozanimod on Symbol Digit Modalities Test Performance in Relapsing MS.
作者信息
DeLuca John, Schippling Sven, Montalban Xavier, Kappos Ludwig, Cree Bruce A C, Comi Giancarlo, Arnold Douglas L, Hartung Hans-Peter, Sheffield James K, Liu Hongjuan, Silva Diego, Cohen Jeffrey A
机构信息
Kessler Foundation, 1199 Pleasant Valley Way, West Orange, NJ 07052 USA and Departments of Physical Medicine and Rehabilitation, and Neurology, Rutgers - New Jersey Medical School, Newark 07103, NJ, USA.
Neuroimmunology and Multiple Sclerosis Research, Department of Neurology, University Hospital and University of Zürich and Neuroscience Center Zürich, University of Zürich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland and Federal Institute of Technology (ETH) Zürich, Rämistrasse 101, 8092 Zürich, Switzerland.
出版信息
Mult Scler Relat Disord. 2021 Feb;48:102673. doi: 10.1016/j.msard.2020.102673. Epub 2020 Dec 10.
BACKGROUND
Cognitive dysfunction, including slowed cognitive processing speed (CPS), is one of the most disabling symptoms of multiple sclerosis (MS). The Symbol Digit Modalities Test (SDMT) is a preferred measure of CPS for MS trials and routine screening. Based on encouraging SDMT results in the phase 3 SUNBEAM trial, these post hoc, exploratory analyses were conducted to further compare effects of the sphingosine 1-phosphate receptor modulator ozanimod versus intramuscular interferon β-1a on CPS in participants with relapsing multiple sclerosis (RMS).
METHODS
In the phase 3, double-blind, double-dummy, SUNBEAM study, adults (aged 18‒55 years) with RMS (N=1,346) were randomized to once-daily oral ozanimod 0.92 or 0.46 mg, or weekly intramuscular interferon β-1a 30 µg. The study continued until the last participant was treated for 12 months. CPS was measured as part of a secondary endpoint using the SDMT. Exploratory, post hoc analyses evaluated SDMT change and percentages of participants with clinically meaningful (≥4-point) SDMT improvement or worsening at months 6 and 12, and relationship between SDMT and brain volume on magnetic resonance imaging.
RESULTS
Ozanimod improved SDMT scores compared with interferon β-1a at months 6 and 12. At month 12, least squares mean difference in SDMT z-scores for ozanimod 0.92 mg versus interferon β-1a was 0.102 (95% CI, 0.031‒0.174, nominal p = 0.0051; standardized mean difference = 0.1376). A greater percentage of ozanimod 0.92 mg‒treated participants had clinically meaningful improvements in SDMT scores versus interferon β-1a at month 6 (30.0% versus 22.2%) and month 12 (35.6% versus 27.9%). Of those with SDMT improvement at month 6, 66.4% of those treated with ozanimod 0.92 mg and 55.9% of those treated with interferon β-1a had sustained improvement at month 12. Brain volume loss was similar for those with SDMT improvement versus worsening at month 12.
CONCLUSIONS
In these exploratory analyses, ozanimod had modestly beneficial effects on CPS in RMS participants. The effects of ozanimod on SDMT are being further evaluated in an ongoing 3-year clinical trial. SUNBEAM is registered on clinicaltrials.gov (NCT02294058) and the European Clinical Trials Database (EudraCT 2014-002320-27).
背景
认知功能障碍，包括认知处理速度减慢（CPS），是多发性硬化症（MS）最具致残性的症状之一。符号数字模态测验（SDMT）是MS试验和常规筛查中用于评估CPS的首选方法。基于3期SUNBEAM试验中令人鼓舞的SDMT结果，进行了这些事后探索性分析，以进一步比较鞘氨醇-1-磷酸受体调节剂奥扎莫德与肌肉注射干扰素β-1a对复发型多发性硬化症（RMS）患者CPS的影响。
方法
在3期双盲、双模拟SUNBEAM研究中，1346例年龄在18至55岁之间的RMS成人患者被随机分为每日口服一次奥扎莫德0.92mg或0.46mg，或每周肌肉注射干扰素β-1a 30μg。研究持续至最后一名参与者接受治疗12个月。使用SDMT作为次要终点的一部分来测量CPS。探索性事后分析评估了第6个月和第12个月时SDMT的变化以及SDMT有临床意义（≥4分）改善或恶化的参与者百分比，以及SDMT与磁共振成像脑容量之间的关系。
结果
在第6个月和第12个月时，与干扰素β-1a相比，奥扎莫德改善了SDMT评分。在第12个月时，奥扎莫德0.92mg与干扰素β-1a的SDMT z评分的最小二乘均值差异为0.102（95%CI，0.031-0.174，名义p=0.0051；标准化均值差异=0.1376）。在第6个月（分别为30.0%和22.2%）和第12个月（分别为35.6%和27.9%），接受奥扎莫德0.92mg治疗的参与者中SDMT评分有临床意义改善的百分比高于干扰素β-1a组。在第6个月SDMT有改善的患者中，接受奥扎莫德0.92mg治疗的患者中有66.4%在第12个月持续改善，接受干扰素β-1a治疗的患者中有55.9%持续改善。在第12个月时，SDMT改善与恶化的患者脑容量损失相似。
结论
在这些探索性分析中，奥扎莫德对RMS患者的CPS有适度有益影响。奥扎莫德对SDMT的影响正在一项正在进行的3年临床试验中进一步评估。SUNBEAM已在ClinicalTrials.gov（NCT02294058）和欧洲临床试验数据库（EudraCT 2014-002320-27）注册。
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