From the Danish Multiple Sclerosis Center (P.S.S.), Rigshospitalet, Copenhagen; Genmab (S.L.), Copenhagen, Denmark; GlaxoSmithKline (R.G.), Uxbridge, Middlesex, UK; GlaxoSmithKline (F.D.), Research Triangle Park; GlaxoSmithKline (S.S.), Raleigh, NC; Charles University (E.H.), Prague, Czech Republic; School of Medicine University of Belgrade (J.D.), Serbia; and San Raffaele Scientific Institute and Vita-Salute San Raffaele University (M.F.), Milan, Italy.
Neurology. 2014 Feb 18;82(7):573-81. doi: 10.1212/WNL.0000000000000125. Epub 2014 Jan 22.
We present the first study to explore safety and efficacy of the human CD20 monoclonal antibody ofatumumab in relapsing-remitting multiple sclerosis (RRMS).
In this randomized, double-blind, placebo-controlled study, patients received 2 ofatumumab infusions (100 mg, 300 mg, or 700 mg) or placebo 2 weeks apart. At week 24, patients received alternate treatment. Safety and efficacy were assessed.
Thirty-eight patients were randomized (ofatumumab/placebo, n = 26; placebo/ofatumumab, n = 12) and analyzed; 36 completed the study. Two patients in the 300-mg group withdrew from the study because of adverse events. No unexpected safety signals emerged. Infusion-related reactions were common on the first infusion day but not observed on the second infusion day. None of the patients developed human anti-human antibodies. Ofatumumab was associated with profound selective reduction of B cells as measured by CD19(+) expression. New brain MRI lesion activity was suppressed (>99%) in the first 24 weeks after ofatumumab administration (all doses), with statistically significant reductions (p < 0.001) favoring ofatumumab found in new T1 gadolinium-enhancing lesions, total enhancing T1 lesions, and new and/or enlarging T2 lesions.
Ofatumumab (up to 700 mg) given 2 weeks apart was not associated with any unexpected safety concerns and was well tolerated in patients with RRMS. MRI data suggest a clinically meaningful effect of ofatumumab for all doses studied. Results warrant further exploration of ofatumumab in RRMS.
This study provides Class II evidence that in patients with RRMS, ofatumumab compared with placebo does not increase the number of serious adverse events and decreases the number of new MRI lesions.
我们首次研究了人源抗 CD20 单克隆抗体奥法妥木单抗在复发缓解型多发性硬化症（RRMS）中的安全性和疗效。
在这项随机、双盲、安慰剂对照研究中，患者接受了 2 次奥法妥木单抗输注（100mg、300mg 或 700mg）或安慰剂，间隔 2 周。在第 24 周，患者接受交替治疗。评估安全性和疗效。
38 名患者被随机分组（奥法妥木单抗/安慰剂，n=26；安慰剂/奥法妥木单抗，n=12）并进行分析；36 名患者完成了研究。300mg 组的 2 名患者因不良事件退出研究。未出现意外的安全性信号。首次输注日常见输注相关反应，但第二次输注日未观察到。无患者产生人抗人抗体。奥法妥木单抗与通过 CD19（+）表达测量的 B 细胞的深度选择性减少相关。在奥法妥木单抗给药后的前 24 周内，新的脑 MRI 病变活动被抑制（所有剂量），新 T1 钆增强病变、总增强 T1 病变以及新的和/或扩大的 T2 病变的统计学显著减少（p＜0.001）均有利于奥法妥木单抗。
间隔 2 周给予奥法妥木单抗（最高 700mg）与任何意外的安全性问题无关，在 RRMS 患者中耐受性良好。MRI 数据表明，奥法妥木单抗对所有研究剂量均具有有临床意义的疗效。结果进一步证实了奥法妥木单抗在 RRMS 中的应用价值。
本研究提供了 II 级证据，表明在 RRMS 患者中，与安慰剂相比，奥法妥木单抗不会增加严重不良事件的数量，并减少新的 MRI 病变数量。
