From the Department of Radiology and Nuclear Medicine (F.B.), VU University Medical Centre, Amsterdam, the Netherlands; UCL Institutes of Healthcare Engineering and Neurology (F.B.), London, UK; Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering (L.K.), University Hospital Basel, University of Basel, Switzerland; Department of Neurology (J.S.W.), McGovern Medical School, UTHealth, Houston, TX; Department of Radiology (D.K.B.L.), University of British Columbia, Vancouver, Canada; Department of Neurology and Center for Neuroinflammation and Experimental Therapeutics (A.B.-O.), University of Pennsylvania, Philadelphia; Department of Neurology, Medical Faculty (H.-P.H.), Heinrich-Heine University Düsseldorf, Germany; F. Hoffmann-La Roche Ltd. (S.B., A.S., J.N., H.K.), Basel, Switzerland; Genentech, Inc. (J.H., L.J.), South San Francisco; and Department of Neurology (S.L.H.), University of California, San Francisco. During completion of the work related to this article, S. Belachew was an employee of F. Hoffmann-La Roche Ltd.; his current affiliation is Biogen, Cambridge, MA.
Neurology. 2019 Nov 5;93(19):e1778-e1786. doi: 10.1212/WNL.0000000000008189. Epub 2019 Sep 4.
To assess the onset of ocrelizumab efficacy on brain MRI measures of disease activity in the phase II study in relapsing-remitting multiple sclerosis (RRMS), and relapse rate in the pooled phase III studies in relapsing multiple sclerosis (RMS).
Brain MRI activity was determined in the phase II trial at monthly intervals in patients with RRMS receiving placebo, ocrelizumab (600 mg), or intramuscular interferon (IFN) β-1a (30 μg). Annualized relapse rate (ARR; over various epochs) and time to first relapse were analyzed in the pooled population of the phase III OPERA (A Study of Ocrelizumab in Comparison With Interferon Beta-1a [Rebif] in Participants With Relapsing Multiple Sclerosis) I and OPERA II trials in patients with RMS receiving ocrelizumab (600 mg) or subcutaneous IFN-β-1a (44 μg).
In patients with RRMS, ocrelizumab reduced the number of new T1 gadolinium-enhancing lesions by week 4 vs placebo ( = 0.042) and by week 8 vs intramuscular IFN-β-1a ( < 0.001). Ocrelizumab also reduced the number of new or enlarging T2 lesions appearing between weeks 4 and 8 vs both placebo and IFN-β-1a (both < 0.001). In patients with RMS, ocrelizumab significantly reduced ARR ( = 0.005) and the probability of time to first protocol-defined relapse ( = 0.014) vs subcutaneous IFN-β-1a within the first 8 weeks.
Epoch analysis of MRI-measured lesion activity in the phase II study and relapse rate in the phase III studies consistently revealed a rapid suppression of acute MRI and clinical disease activity following treatment initiation with ocrelizumab in patients with RRMS and RMS, respectively.
This study provides Class II evidence that for patients with RRMS and RMS, ocrelizumab suppressed MRI activity within 4 weeks and clinical disease activity within 8 weeks.
评估奥瑞珠单抗在复发缓解型多发性硬化症（RRMS）的 II 期研究中对脑部磁共振成像（MRI）疾病活动指标的疗效起始时间，以及在复发型多发性硬化症（RMS）的 III 期汇总研究中的复发率。
在 RRMS 患者中，II 期试验每月进行一次脑部 MRI 活动评估，患者分别接受安慰剂、奥瑞珠单抗（600mg）或肌肉内干扰素（IFN）β-1a（30μg）治疗。在 RMS 患者中，分析汇总的 III 期 OPERA（奥瑞珠单抗与干扰素β-1a[Rebif]在复发多发性硬化症患者中的比较研究）I 期和 OPERA II 期研究中接受奥瑞珠单抗（600mg）或皮下 IFN-β-1a（44μg）治疗患者的年化复发率（ARR；各时期）和首次复发时间。
在 RRMS 患者中，奥瑞珠单抗在第 4 周时较安慰剂减少了新的 T1 钆增强病变数量（ = 0.042），在第 8 周时较肌肉内 IFN-β-1a 减少（ < 0.001）。奥瑞珠单抗还减少了第 4 至 8 周之间出现的新的或扩大的 T2 病变数量，与安慰剂和 IFN-β-1a 相比，均有统计学意义（均 < 0.001）。在 RMS 患者中，奥瑞珠单抗在第 8 周内显著降低了 ARR（ = 0.005）和首次发生方案定义的复发时间（ = 0.014），与皮下 IFN-β-1a 相比。
II 期研究中 MRI 测量的病变活动的区间分析和 III 期研究中的复发率结果一致表明，在 RRMS 和 RMS 患者中，分别在奥瑞珠单抗治疗起始后 4 周和 8 周内迅速抑制了急性 MRI 和临床疾病活动。
这项研究提供了 II 级证据，证明对于 RRMS 和 RMS 患者，奥瑞珠单抗在 4 周内抑制 MRI 活动，在 8 周内抑制临床疾病活动。
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