美国加州大学Stephen L. Hauser联合瑞士巴塞尔大学医院Ludwig Kappos团队比较了奥法木单抗和特立氟胺治疗多发性硬化症的疗效。2020年8月6日，该研究发表在《新英格兰医学杂志》上。

奥法木单抗是一类皮下抗CD20单克隆抗体，可选择性消耗B细胞。特立氟胺是一类嘧啶合成的口服抑制剂，可减少T细胞和B细胞活化。尚不清楚这两种药物是否对多发性硬化症患者有益处。

研究组进行了两项双盲、双模拟的3期临床试验，招募患有复发性多发性硬化症的患者，将其随机分组，其中946例接受奥法木单抗治疗，936例接受特立氟胺治疗，均为期30个月。主要终点是年化复发率。

中位随访1.6年后，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，差异显著；试验2中奥法木单抗组和特立氟胺组的年复发率分别为0.10和0.25，差异亦显著。

在汇总试验中，奥法木单抗组治疗3个月时确认残疾恶化的患者占10.9%，显著低于特立氟胺组（15.0%）；治疗6个月时确认残疾恶化的患者占8.1%，显著低于特立氟胺组（12.0%）；治疗6个月时确认残疾改善的患者占11.0%，特立氟胺组为8.1%，差异不显著。

奥法木单抗组每次T1加权MRI扫描增强病变的数量，T2加权MRI病变的年化率，以及血清神经丝轻链水平，均优于特立氟胺组，但脑容量的变化除外。奥法木单抗组注射相关反应的发生率为20.2%，特立氟胺组为15.0%。两组中分别有2.5%和1.8%的患者发生严重感染。

研究结果表明，奥法木单抗治疗多发性硬化症患者，年复发率显著低于特立氟胺。

附：英文原文

Title: Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author: Stephen L. Hauser, M.D.,, Amit Bar-Or, M.D.,, Jeffrey A. Cohen, M.D.,, Giancarlo Comi, M.D.,, Jorge Correale, M.D.,, Patricia K. Coyle, M.D.,, Anne H. Cross, M.D.,, Jerome de Seze, M.D.,, David Leppert, M.D.,, Xavier Montalban, M.D.,, Krzysztof Selmaj, M.D.,, Heinz Wiendl, M.D.,, Cecile Kerloeguen, M.Sc.,, Roman Willi, Ph.D.,, Bingbing Li, Ph.D.,, Algirdas Kakarieka, M.D.,, Davorka Tomic, D.V.M.,, Alexandra Goodyear, M.D.,, Ratnakar Pingili, M.B., B.S.,, Dieter A. Hring, Ph.D.,, Krishnan Ramanathan, Ph.D.,, Martin Merschhemke, M.D.,, and Ludwig Kappos, M.D.

Issue&Volume: 2020-08-05

Abstract: 

Background

Ofatumumab, 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.

Methods

In 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.

Results

Overall, 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<0.001) and 0.10 and 0.25 in trial 2 (difference, 0.15; 95% CI, 0.20 to 0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P=0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P=0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P=0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups.

Conclusions

Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide.

DOI: 10.1056/NEJMoa1917246

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1917246