Zivadinov Robert, Dwyer Michael G, Carl Ellen, Poole Elizabeth M, Cavalier Steve, Briassouli Paraskevi, Bergsland Niels
Buffalo Neuroimaging Analysis Center, State University of New York, 100 High St, Buffalo, NY 14203, USA.
The Buffalo Neuroimaging Analysis Center Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
Ther Adv Neurol Disord. 2020 Nov 11;13:1756286420970754. doi: 10.1177/1756286420970754. eCollection 2020.
We explored the effect of teriflunomide on cortical gray matter (CGM) and whole brain (WB) atrophy in patients with clinically isolated syndrome (CIS) from the phase III TOPIC study and assessed the relationship between atrophy and risk of conversion to clinically definite MS (CDMS).
Patients (per McDonald 2005 criteria) were randomized 1:1:1 to placebo, teriflunomide 7 mg, or teriflunomide 14 mg for ⩽108 weeks (core study). In the extension, teriflunomide-treated patients maintained their original dose; placebo-treated patients were re-randomized 1:1 to teriflunomide 7 mg or 14 mg. Brain volume was assessed during years 1-2.
Teriflunomide 14 mg significantly slowed annualized CGM and WB atrophy placebo during years 1-2 [percent reduction: month 12, 61.4% (CGM; = 0.0359) and 28.6% (WB; = 0.0286); month 24, 40.2% (CGM; = 0.0416) and 43.0% (WB; < 0.0001)]. For every 1% decrease in CGM or WB volume during years 1-2, risk of CDMS conversion increased by 14.5% (=0.0004) and 47.3% (< 0.0001) during years 1-2, respectively, and 6.6% (=0.0570) and 35.9% (= 0.0250) during years 1-5. In patients with the least (bottom quartile) most (top quartile) atrophy during years 1-2, risk of CDMS conversion was reduced by 58% (CGM; = 0.0024) and 58% (WB; = 0.0028) during years 1-2, and 42% (CGM; = 0.0138) and 29% (WB; = 0.1912) during years 1-5.
These findings support the clinical relevance of CGM and WB atrophy and early intervention with teriflunomide in CIS.
我们在III期TOPIC研究中探讨了特立氟胺对临床孤立综合征（CIS）患者皮质灰质（CGM）和全脑（WB）萎缩的影响，并评估了萎缩与转化为临床确诊多发性硬化症（CDMS）风险之间的关系。
患者（根据2005年麦克唐纳标准）按1:1:1随机分为安慰剂组、7毫克特立氟胺组或14毫克特立氟胺组，治疗时间≤108周（核心研究）。在延长期，接受特立氟胺治疗的患者维持原剂量；接受安慰剂治疗的患者按1:1重新随机分为7毫克或14毫克特立氟胺组。在第1至2年评估脑容量。
在第1至2年，14毫克特立氟胺显著减缓了CGM和WB的年化萎缩速度，优于安慰剂组[萎缩率降低百分比：第12个月，CGM为61.4%（P = 0.0359），WB为28.6%（P = 0.0286）；第24个月，CGM为40.2%（P = 0.0416），WB为43.0%（P < 0.0001）]。在第1至2年，CGM或WB体积每减少1%，CDMS转化风险分别增加14.5%（P = 0.0004）和47.3%（P < 0.0001），在第1至5年分别增加6.6%（P = 0.0570）和35.9%（P = 0.0250）。在第1至2年萎缩最少（四分位间距底部）或最多（四分位间距顶部）的患者中，在第1至2年CDMS转化风险降低了58%（CGM；P = 0.0024）和58%（WB；P = 0.0028），在第1至5年分别降低了42%（CGM；P = 0.0138）和29%（WB；P = 0.1912）。
这些发现支持了CGM和WB萎缩的临床相关性以及在CIS中使用特立氟胺进行早期干预的必要性。
