Multiple Sclerosis Center of the 2nd Neurological University Department, School of Medicine, Aristotle University of Thessaloniki, AHEPA General University Hospital, 54636 Thessaloniki, Greece.
Microbiology Laboratory, Department of Immunology, AHEPA University Hospital, 54636 Thessaloniki, Greece.
Cells. 2022 Jun 17;11(12):1959. doi: 10.3390/cells11121959.
Ocrelizumab is a B-cell-depleting monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (RRMS) and active primary progressive MS (aPPMS). This prospective, uncontrolled, open-label, observational study aimed to assess the efficacy of ocrelizumab in patients with aPPMS and to dissect the clinical, radiological and laboratory attributes of treatment response. In total, 22 patients with aPPMS followed for 24 months were included. The primary efficacy outcome was the proportion of patients with optimal response at 24 months, defined as patients free of relapses, free of confirmed disability accumulation (CDA) and free of T1 Gd-enhancing lesions and new/enlarging T2 lesions on the brain and cervical MRI. In total, 14 (63.6%) patients and 13 patients (59.1%) were classified as responders at 12 and 24 months, respectively. Time exhibited a significant effect on mean absolute and normalized gray matter cerebellar volume (F = 4.342, = 0.23 and F = 4.279, = 0.024, respectively). Responders at 24 months exhibited reduced peripheral blood ((%) of CD19+ cells) plasmablasts compared to non-responders at the 6-month point estimate (7.69 ± 4.4 vs. 22.66 ± 7.19, respectively, = 0.043). Response to ocrelizumab was linked to lower total and gray matter cerebellar volume loss over time. Reduced plasmablast depletion was linked for the first time to sub-optimal response to ocrelizumab in aPPMS.
奥瑞珠单抗是一种 B 细胞耗竭型单克隆抗体，已被批准用于治疗复发缓解型多发性硬化症（RRMS）和活跃的原发性进展型多发性硬化症（aPPMS）。这项前瞻性、非对照、开放标签、观察性研究旨在评估奥瑞珠单抗在 aPPMS 患者中的疗效，并剖析治疗反应的临床、影像学和实验室特征。共纳入 22 例随访 24 个月的 aPPMS 患者。主要疗效结局为 24 个月时达到最佳反应的患者比例，定义为无复发、无确诊残疾进展（CDA）且脑和颈 MRI 上无 T1 Gd 增强病变和新/扩大 T2 病变的患者。共有 14 例（63.6%）和 13 例（59.1%）患者分别在 12 个月和 24 个月时被归类为应答者。时间对平均绝对和归一化小脑灰质体积（F = 4.342， = 0.23 和 F = 4.279， = 0.024）有显著影响。24 个月时的应答者与 6 个月时的非应答者相比，外周血（%的 CD19+细胞）浆母细胞减少（7.69 ± 4.4 与 22.66 ± 7.19， = 0.043）。奥瑞珠单抗的应答与随时间推移总体积和小脑灰质体积的减少相关。浆母细胞耗竭减少与 aPPMS 中奥瑞珠单抗的亚最佳应答首次相关。
