Hartung H-P, Berger T, Bermel R A, Brochet B, Carroll W M, Holmøy T, Karabudak R, Killestein J, Nos C, Patti F, Ross A Perrin, Vanopdenbosch L, Vollmer T, Buffels R, Garas M, Kadner K, Manfrini M, Wang Q, Freedman M S
Department of Neurology, UKD, Center of Neurology and Neuropsychiatry and LVR-Klinikum, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20 1090 Vienna, Austria.
Mult Scler Relat Disord. 2020 Nov;46:102492. doi: 10.1016/j.msard.2020.102492. Epub 2020 Sep 24.
Ocrelizumab is an approved intravenously administered anti-CD20 antibody for multiple sclerosis (MS). Shortening the 600 mg infusion to 2 hours reduces the total site stay from 5.5-6 hours (approved infusion duration including mandatory pre-medication and post-infusion observation) to 4 hours. The safety profile of shorter-duration ocrelizumab infusions was investigated using results from ENSEMBLE PLUS.
ENSEMBLE PLUS is a randomized, double-blind substudy to the single-arm ENSEMBLE study (NCT03085810). In ENSEMBLE, patients with early-stage relapsing-remitting MS received ocrelizumab 600 mg infusions every 24 weeks for 192 weeks. In ENSEMBLE PLUS, ocrelizumab 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration); the durations of the initial infusions (2×300 mg, 14 days apart) were unaffected. The primary endpoint was the proportion of patients with infusion-related reactions (IRRs) following the first Randomized Dose.
From November 1, 2018, to December 13, 2019, 745 patients were randomized 1:1 to the conventional or shorter infusion group. At the first Randomized Dose, 99/373 patients (26.5%) in the conventional and 107/372 patients (28.8%) in the shorter infusion group experienced IRRs. The majority of IRRs were mild or moderate; >99% of all IRRs resolved without sequelae in both groups (conventional infusion group, 99/99; shorter infusion group, 106/107). No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuations occurred. During the first Randomized Dose, 22/373 (5.9%) and 39/372 (10.5%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption. Adverse events were consistent with the known safety profile of ocrelizumab.
The rates and severity of IRRs were similar between conventional and shorter infusions. No new safety signals were detected. Shortening the infusion time to 2 hours reduces the total site stay time (including mandatory pre-medication/infusion/observation) from 5.5-6 hours to 4 hours, and may reduce patient and site staff burden. A short video summarizing the key results is provided in supplemental material.
奥瑞珠单抗是一种已获批准的用于治疗多发性硬化症（MS）的静脉注射抗CD20抗体。将600毫克的输注时间缩短至2小时，可使总停留时间从5.5 - 6小时（包括强制性的用药前准备和输注后观察的批准输注时间）减少至4小时。利用ENSEMBLE PLUS的结果对较短时间的奥瑞珠单抗输注的安全性进行了研究。
ENSEMBLE PLUS是单臂ENSEMBLE研究（NCT03085810）的一项随机、双盲子研究。在ENSEMBLE研究中，复发缓解型早期MS患者每24周接受一次600毫克奥瑞珠单抗输注，共192周。在ENSEMBLE PLUS研究中，将在批准的3.5小时输注时间（常规时间）内给予的600毫克奥瑞珠单抗与2小时输注（较短时间）进行比较；初始输注（2×300毫克，间隔14天）的时间不受影响。主要终点是首次随机剂量后发生输注相关反应（IRR）的患者比例。
从2018年11月1日至2019年12月13日，745例患者按1:1随机分为常规输注组或较短输注组。在首次随机剂量时，常规输注组373例患者中有99例（26.5%），较短输注组372例患者中有第107例（28.8%）发生IRR。大多数IRR为轻度或中度；两组中所有IRR的>99%均无后遗症地得到缓解（常规输注组，99/99；较短输注组，106/107）。没有IRR是严重、危及生命或致命的。没有发生与IRR相关的停药情况。在首次随机剂量期间，常规输注组和较短输注组分别有22/373（5.9%）和39/372（10.5%）的患者因IRR导致输注减慢/中断。不良事件与奥瑞珠单抗已知的安全性特征一致。
常规输注和较短输注之间IRR的发生率和严重程度相似。未检测到新的安全信号。将输注时间缩短至2小时可使总停留时间（包括强制性的用药前准备/输注/观察）从5.5 - 6小时减少至4小时，并可能减轻患者和现场工作人员的负担。补充材料中提供了一个总结关键结果的短视频。
