Ocrelizumab是一种人源化抗CD20单克隆抗体,用于治疗多发性硬化症(MS)。它于2017年3月获得美国食品和药物管理局(FDA)的批准,用于复发缓解型多发性硬化症(RRMS)和原发性进行性多发性硬化症(PPMS)的成人。Ocrelizumab是唯一批准用于PPMS的疾病改善疗法(DMT)。2017年11月,欧洲药品管理局(EMA)也批准奥克瑞珠单抗作为早期PPMS患者的第一个药物。因此,评估收益很重要,危害,奥克瑞珠单抗在MS患者中的耐受性
为了评估收益,危害,奥克瑞珠单抗在RRMS和PPMS患者中的耐受性。
我们搜索了MEDLINE,Embase,中部,和2021年10月8日的两项审判登记。我们筛选了参考名单,联系专家,并联系了研究的主要作者。
所有随机对照试验(RCT)涉及根据McDonald标准诊断为RRMS或PPMS的成人,比较奥利珠单抗单独或与其他药物相关,在任何持续时间内每24周600毫克的批准剂量,与安慰剂或任何其他活性药物治疗相比。
我们使用了Cochrane期望的标准方法学程序。
四个RCT符合我们的选择标准。总体人群包括2551名参与者;1370名接受奥克瑞珠单抗600mg治疗,1181名对照。在控件中,298名参与者接受安慰剂,883名参与者接受干扰素β-1a。在一项研究中,治疗持续时间为24周,两项研究共96周,在一项研究中至少有120周。一项研究对参与者和人员进行分配隐藏和致盲的风险很高;所有四项研究对不完整的结果数据都有很高的偏倚风险。对于RRMS,与干扰素β-1a相比,ocrelizumab与:1.较低的复发率(风险比(RR)0.61,95%置信区间(CI)0.52至0.73;2项研究,1656名参与者;中等确定性证据);2。残疾进展的参与者人数较少(风险比(HR)0.60,95%CI0.43至0.84;2项研究,1656名参与者;低确定性证据);3。有任何不良事件的参与者人数几乎没有差异(RR1.00,95%CI0.96至1.04;2项研究,1651名参与者;中等确定性证据);4。有任何严重不良事件的参与者人数几乎没有差异(RR0.79,95%CI0.57至1.11;2项研究,1651名参与者;低确定性证据);5。因不良事件而停止治疗的参与者人数较少(RR0.58,95%CI0.37至0.91;2项研究,1651名参与者;低确定性证据);6。磁共振成像(MRI)上钆增强T1病变的参与者数量较少(RR0.27,95%CI0.22至0.35;2项研究,1656名参与者;低确定性证据);7.在MRI上出现新的或扩大的T2-高强度病变的参与者数量较少(RR0.63,95%CI0.57至0.69;2项研究,1656名参与者;低确定性证据)在96周。对于PPMS,与安慰剂相比,ocrelizumab与:1.残疾进展的参与者人数较少(HR0.75,95%CI0.58至0.98;1项研究,731名参与者;低确定性证据);2。有任何不良事件的参与者数量较多(RR1.06,95%CI1.01~1.11;1项研究,725名参与者;中等确定性证据);3。发生任何严重不良事件的参与者人数几乎没有差异(RR0.92,95%CI0.68至1.23;1项研究,725名参与者;低确定性证据);4。经历不良事件导致的治疗中断的参与者人数几乎没有差异(RR1.23,95%CI0.55至2.75;1项研究,725名参与者;低确定性证据)至少120周。没有关于MRI上有钆增强T1病变的参与者数量和MRI上有新的或扩大的T2高强度病变的参与者数量的数据。
对于有RRMS的人,与96周时的干扰素β-1a相比,奥克瑞珠单抗可能导致复发率大幅降低,不良事件几乎没有差异(中度确定性证据).Ocrelizumab可能导致残疾进展的大幅减少,由不良事件引起的治疗中断,MRI上钆增强T1病变的参与者数量,以及MRI上出现新的或扩大的T2高强度病变的参与者数量,并且可能导致严重不良事件几乎没有差异(低确定性证据)。对于PPMS患者,与安慰剂组相比,至少120周的奥克瑞珠单抗可能导致更高的不良事件发生率(中度确定性证据).Ocrelizumab可能导致残疾进展减少,严重不良事件和不良事件引起的治疗中断几乎没有差异(低确定性证据)。Ocrelizumab在临床上耐受良好;最常见的不良事件是输注相关反应和鼻咽炎,泌尿道和上呼吸道感染。
Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS.
To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS.
We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies.
All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy.
We used standard methodological procedures expected by Cochrane.
Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI.
For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.