Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Department of Neurology, Focus Program Translational Neuroscience (FTN), and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
Med. 2023 Jun 9;4(6):361-372.e3. doi: 10.1016/j.medj.2023.05.001. Epub 2023 May 25.
Long-term B cell depletion with ocrelizumab in multiple sclerosis (MS) is associated with severe side effects such as hypogammaglobulinemia and infections. Our study therefore aimed to assess immunoglobulin levels under treatment with ocrelizumab and implement an extended interval dosing (EID) scheme.
Immunoglobulin levels of 51 patients with ≥24 months of treatment with ocrelizumab were analyzed. After ≥4 treatment cycles, patients chose to either continue on the standard interval dosing (SID) regimen (n = 14) or, in the case of clinically and radiologically stable disease, switch to B cell-adapted EID (n = 12, next dose at CD19 B cells >1% of peripheral blood lymphocytes).
Levels of immunoglobulin M (IgM) declined rapidly under ocrelizumab treatment. Risk factors for IgM and IgA hypogammaglobulinemia were lower levels at baseline and more previous disease-modifying therapies. B cell-adapted EID of ocrelizumab increased the mean time until next infusion from 27.3 to 46.1 weeks. Ig levels declined significantly in the SID group over 12 months but not in the EID group. Previously stable patients remained stable under EID as measured by expanded disability status scale (EDSS), neurofilament light chain, timed 25-foot walk (T25-FW), 9-hole peg test (9-HPT), symbol digit modalities test (SDMT), and multiple sclerosis impact scale (MSIS-29).
In our pilot study, B cell-adapted EID of ocrelizumab prevented the decline of Ig levels without affecting disease activity in previously stable patients with MS. Based on these findings, we propose a new algorithm for long-term ocrelizumab treatment.
This study was supported by the Deutsche Forschungsgemeinschaft (SFB CRC-TR-128, SFB 1080, and SFB CRC-1292) and the Hertie Foundation.
奥瑞珠单抗在多发性硬化症（MS）中的长期 B 细胞耗竭与低丙种球蛋白血症和感染等严重副作用相关。因此，我们的研究旨在评估奥瑞珠单抗治疗下的免疫球蛋白水平，并实施扩展间隔给药（EID）方案。
分析了 51 例接受奥瑞珠单抗治疗≥24 个月的患者的免疫球蛋白水平。在≥4 个治疗周期后，患者选择继续接受标准间隔剂量（SID）方案（n=14），或者在疾病和影像学稳定的情况下，转换为 B 细胞适应的 EID（n=12，下一次剂量在 CD19 B 细胞＞外周血淋巴细胞的 1%时）。
奥瑞珠单抗治疗下，免疫球蛋白 M（IgM）水平迅速下降。IgM 和 IgA 低丙种球蛋白血症的危险因素是基线水平较低和更多先前的疾病修正治疗。奥瑞珠单抗的 B 细胞适应 EID将下一次输注的平均时间从 27.3 周延长至 46.1 周。SID 组在 12 个月内 Ig 水平显著下降，但 EID 组没有。根据扩展残疾状态量表（EDSS）、神经丝轻链、25 英尺步行计时测试（T25-FW）、9 孔钉测试（9-HPT）、符号数字模态测试（SDMT）和多发性硬化症影响量表（MSIS-29），先前稳定的患者在 EID 下仍保持稳定。
在我们的初步研究中，奥瑞珠单抗的 B 细胞适应 EID 防止了 Ig 水平的下降，而没有影响先前稳定的多发性硬化症患者的疾病活动。基于这些发现，我们提出了一种新的奥瑞珠单抗长期治疗算法。
本研究得到德国研究基金会（SFB CRC-TR-128、SFB 1080 和 SFB CRC-1292）和赫蒂基金会的支持。
