From the Department of Neurology, UKD, Center of Neurology and Neuropsychiatry and LVR-Klinikum, Medical Faculty, Heinrich-Heine University Düsseldorf, Germany.
Neurol Neuroimmunol Neuroinflamm. 2020 Jun 4;7(5). doi: 10.1212/NXI.0000000000000807. Print 2020 Sep.
To assess the safety of ocrelizumab (OCR) shorter duration infusion in patients with MS.
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 OCR 600 mg initially as two 300 mg IV infusions 2 weeks apart and subsequently as a single 3.5-hour 600 mg infusion every 24 weeks for 192 weeks. In ENSEMBLE PLUS, OCR 600 mg administered over the approved 3.5-hour infusion time (conventional duration) is compared with a 2-hour infusion (shorter duration). The primary end point was the proportion of patients with infusion-related reactions (IRRs) after the first randomized dose (assessed during and up to 24 hours postinfusion).
From November 1, 2018, to September 27, 2019, 580 patients were randomized 1:1 to the conventional or shorter infusion group. After the first randomized dose, 67 of 291 patients (23.1%) in the conventional and 71 of 289 patients (24.6%) in the shorter infusion group experienced IRRs. Most IRRs were mild or moderate in both groups; one patient in each group experienced a severe IRR, and in both groups, 98.6% (136 of 138) of all IRRs resolved without sequelae. No IRRs were serious, life-threatening, or fatal. No IRR-related discontinuation occurred. During the first randomized dose, 14 of 291 (4.8%) and 25 of 289 (8.7%) patients in the conventional and shorter infusion groups, respectively, had IRRs leading to infusion slowing/interruption.
The frequency and severity of IRRs were similar between conventional and shorter OCR infusions. Shortening the infusion time to 2 hours reduces the total infusion site stay time and lessens the overall patient and site staff burden.
This interventional study provides Class I evidence that the frequency and severity of IRRs were similar at the first randomized dose using OCR (600 mg) infusions of conventional and shorter duration in patients with relapsing-remitting MS.
NCT03085810.
评估奥瑞珠单抗（OCR）较短输注时间在多发性硬化症患者中的安全性。
ENSEMBLE PLUS 是一项对单臂 ENSEMBLE 研究（NCT03085810）的随机、双盲亚研究。在 ENSEMBLE 中，早期复发缓解型多发性硬化症患者最初接受 OCR600mg，2 周内接受两次 300mg 静脉输注，随后每 24 周接受一次单次 3.5 小时 600mg 输注，共 192 周。在 ENSEMBLE PLUS 中，比较了批准的 3.5 小时输注时间（常规时间）内给予的 OCR600mg 与 2 小时输注（较短时间）。主要终点是首次随机剂量后输注相关反应（IRR）的患者比例（输注期间和输注后 24 小时内评估）。
从 2018 年 11 月 1 日至 2019 年 9 月 27 日，580 名患者以 1:1 的比例随机分为常规或较短输注组。首次随机剂量后，常规组 291 名患者中有 67 名（23.1%）和较短组 289 名患者中有 71 名（24.6%）发生 IRR。两组的大多数 IRR 均为轻度或中度；两组各有 1 例患者发生严重 IRR，两组所有 IRR 中 98.6%（138 例中有 136 例）均无后遗症消退。没有 IRR 是严重的、危及生命的或致命的。没有与 IRR 相关的停药。在首次随机剂量时，常规组和较短组分别有 14 名（4.8%）和 25 名（8.7%）患者发生导致输注减慢/中断的 IRR。
OCR（600mg）常规和较短输注的首次随机剂量的 IRR 频率和严重程度相似。将输注时间缩短至 2 小时可减少总输注部位停留时间，并减轻患者和医护人员的整体负担。
这项干预性研究提供了 I 级证据，表明在复发缓解型多发性硬化症患者中，使用 OCR（600mg）输注时，常规和较短持续时间的 IRR 频率和严重程度在首次随机剂量时相似。
NCT03085810。
