Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
Acta Neurol Belg. 2024 Feb;124(1):205-212. doi: 10.1007/s13760-023-02366-z. Epub 2023 Sep 15.
Ocrelizumab is a humanized antiCD20, thought to be a highly effective disease-modifying therapy (DMT). Its most frequent adverse effects are infusion-related reactions (IRRs). To reduce these reactions, the first dose of ocrelizumab is administered as two 300 mg infusions separated by two weeks. However, in the phase II trial of ocrelizumab, severe IRRs were not significantly different between two doses of 600 mg dose (two separate 300 mg doses) and 2000 mg dose (two separate 1000 mg doses). We compared the IRRs in undivided full (one 600 mg) and divided (two 300 mg) doses of ocrelizumab which is the standard protocol.
MS patients (relapsing or primary progressive MS) who are selected to receive ocrelizumab by neurologist or MS fellowship were enrolled in an open-label randomized controlled trial. Iranian biosimilar of the drug (Xacrel by Cinnagen, approved by the Iranian Food and Drug Administration in 2021) was used. The participants received the first dose of ocrelizumab as either one 600 mg dose in one session or two 300 mg doses in two weeks apart. IRRs during or in the first 24 h after infusion were recorded.
Of 332 participants, 150 received two 300 mg doses, and 182 received one 600 mg dose (by random selection). Life-threatening adverse effects were not observed in both groups. Overnight admission or permanent drug discontinuation was not needed. Temporary drug discontinuation was significantly higher in the one 600 mg dose group (p-value < 0.001). During the infusions, malaise (p-value: 0.003), skin reactions (p-value: 0.04), throat swelling (p-value: 0.03), and dyspnea (p-value: 0.01) were significantly increased in the intervention group. However, in the first 24 h, there was no significant difference between two different treatment protocols (one 600 mg dose or two 300 mg doses) in the onset of IRRS (p-value: 0.12).
These findings suggest one 600 mg dose of ocrelizumab administration for the first dose is relatively safe. With some protocol modifications, it could lead to fewer patient referrals, saving time and cost and improvement the access for patients.
奥瑞珠单抗是一种人源化抗 CD20 单克隆抗体，被认为是一种非常有效的疾病修正疗法（DMT）。其最常见的不良反应是输注相关反应（IRR）。为了减少这些反应，奥瑞珠单抗的首剂量分两剂给药，每剂 300mg，间隔两周。然而，在奥瑞珠单抗的 II 期临床试验中，两剂 600mg 剂量（两剂 300mg）和两剂 1000mg 剂量（两剂 1000mg）之间严重的 IRR 无显著差异。我们比较了未分割的全剂量（一剂 600mg）和分割剂量（两剂 300mg）奥瑞珠单抗的 IRR，这是标准方案。
选择接受奥瑞珠单抗治疗的 MS 患者（复发型或原发性进展型 MS）由神经科医生或 MS 研究员纳入一项开放标签随机对照试验。该研究使用了伊朗仿制药（Xacrel，由 Cinnagen 生产，于 2021 年获得伊朗食品和药物管理局批准）。参与者接受奥瑞珠单抗首剂量，一次 600mg 剂量或两剂 300mg 剂量，间隔两周。记录输注期间或输注后 24 小时内的 IRR。
在 332 名参与者中，150 名接受两剂 300mg 剂量，182 名接受一剂 600mg 剂量（随机选择）。两组均未观察到危及生命的不良反应。不需要住院过夜或永久性停药。一剂 600mg 剂量组的药物暂时停药显著更高（p 值<0.001）。在输注过程中，干预组的不适（p 值：0.003）、皮肤反应（p 值：0.04）、喉咙肿胀（p 值：0.03）和呼吸困难（p 值：0.01）显著增加。然而，在 24 小时内，两种不同治疗方案（一剂 600mg 剂量或两剂 300mg 剂量）之间的 IRR 起始无显著差异（p 值：0.12）。
这些发现表明，首剂给予奥瑞珠单抗 600mg 剂量相对安全。通过一些方案修改，可以减少患者转诊，节省时间和成本，改善患者的获得性。
