Ofatumumab versus Teriflunomide in Multiple Sclerosis
Ofatumumab versus Teriflunomide in Multiple Sclerosis
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DOI：
10.1056/nejmoa1917246
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发表时间：
2020-08-06
影响因子：
158.5
通讯作者：
Kappos, Ludwig
中科院分区：
文献类型：
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作者：
Hauser, Stephen L.;Bar-Or, Amit;Kappos, Ludwig
背景奥法木单抗是一种皮下注射的抗CD 20单克隆抗体，可选择性地清除B细胞。特立氟胺是一种嘧啶合成的口服抑制剂，可减少T细胞和B细胞的活化。这两种药物在多发性硬化症患者的相对影响是未知的。MethodsIn两个双盲，双模拟，3期试验，我们随机分配复发性多发性硬化症患者接受皮下奥法木单抗（20毫克，每4周后20毫克负荷剂量在第1，7和14天）或口服特立氟胺（14毫克，每天）长达30个月。主要终点是年复发率。次要终点包括3个月或6个月时确认的残疾恶化，6个月时确认的残疾改善，T1加权磁共振成像（MRI）扫描的钆增强病变数量，T2加权MRI上新发或扩大病变的年化率，3个月时的血清神经丝轻链水平和脑体积的变化。946例患者被分配接受奥法木单抗治疗，936例接受特立氟胺治疗;中位随访时间为1.6年。在试验1中，奥法木单抗组和特立氟胺组的年复发率分别为0.11和0.22（差异，-0.11; 95%置信区间[CI]，-0.16至-0.06; P
BackgroundOfatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.MethodsIn two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.ResultsOverall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P