Wolinsky Jerry S, Engmann Natalie J, Pei Jinglan, Pradhan Ashish, Markowitz Clyde, Fox Edward J
McGovern Medical School, The University of Texas Health Science Center at Houston, TX, USA.
Genentech, Inc., South San Francisco, CA, USA.
Mult Scler J Exp Transl Clin. 2020 Mar 16;6(1):2055217320911939. doi: 10.1177/2055217320911939. eCollection 2020 Jan-Mar.
Ocrelizumab, an anti-CD20 humanized monoclonal antibody, reduced disease progression in pivotal trials of patients with relapsing (OPERA I, OPERA II) and primary progressive (ORATORIO) multiple sclerosis (MS). These effects may be particularly important among patients with increased disability.
In this post hoc exploratory analysis, we evaluated the efficacy of ocrelizumab on disability progression among a subgroup of patients with MS who had increased baseline disability levels (Expanded Disability Status Scale scores ≥4.0) in the pivotal trials.
During the double-blind period, patients received ocrelizumab 600 mg intravenously every 24 weeks for 96 weeks in the OPERA trials (versus interferon β-1a 44 μg subcutaneously three times per week) and for 120 weeks in ORATORIO (versus placebo). Kaplan-Meier and Cox survival analyses were used to assess disability outcome measures.
Baseline demographic, disease, and treatment characteristics were generally comparable across treatment groups in patients with increased disability from the OPERA and ORATORIO trials. Ocrelizumab treatment numerically, and in some instances significantly, reduced confirmed disability progression versus the comparator in these patients.
In patients with increased baseline disability, ocrelizumab reduced the risk of confirmed disability progression versus interferon β-1a in patients with relapsing-onset MS and versus placebo in patients with progression-onset MS.
奥瑞珠单抗是一种抗CD20人源化单克隆抗体，在复发型（OPERA I、OPERA II）和原发进展型（ORATORIO）多发性硬化症（MS）患者的关键试验中降低了疾病进展。这些作用在残疾程度增加的患者中可能尤为重要。
在这项事后探索性分析中，我们评估了奥瑞珠单抗在关键试验中对基线残疾水平增加（扩展残疾状态量表评分≥4.0）的MS患者亚组中残疾进展的疗效。
在双盲期，OPERA试验中的患者每24周静脉注射600 mg奥瑞珠单抗，持续96周（对比皮下注射每周3次44μg的干扰素β-1a），ORATORIO试验中的患者持续120周（对比安慰剂）。采用Kaplan-Meier和Cox生存分析来评估残疾结局指标。
来自OPERA和ORATORIO试验的残疾程度增加的患者中，各治疗组的基线人口统计学、疾病和治疗特征总体上具有可比性。在这些患者中，与对照相比，奥瑞珠单抗治疗在数值上，且在某些情况下显著降低了确诊的残疾进展。
在基线残疾程度增加的患者中，与复发型MS患者中的干扰素β-1a以及进展型MS患者中的安慰剂相比，奥瑞珠单抗降低了确诊残疾进展的风险。
