Department of Neuroscience, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, 00185 Rome, Italy.
IRCCS Istituto Neurologico Mediterraneo Neuromed, 86077 Pozzilli, Italy.
Int J Mol Sci. 2024 May 14;25(10):5353. doi: 10.3390/ijms25105353.
Ocrelizumab (OCR), an anti-CD20 monoclonal antibody, is approved for treating relapsing remitting (RR) and primary progressive (PP) multiple sclerosis (MS). The standard interval dosing (SID) regimen requires intravenous infusions every six months. Experience of extended dosing due to COVID-19 pandemic-related issues suggests that this strategy may provide comparable efficacy while reducing treatment burden and healthcare costs. This study aimed to evaluate clinical effectiveness, changes in B- and T-cell count, and immunoglobulin dynamics associated with extended interval dosing (EID) of ocrelizumab in a real-world setting. We retrospectively included RRMS or PPMS patients treated with OCR that had already received two OCR cycles and with at least 6 months of follow up after the last infusion. EID was defined as a ≥4 weeks delay compared to SID. Clinical outcomes were occurrence of relapses, MRI activity, 6-months confirmed disability progression (CDP) and their combination (No Evidence of Disease Activity, NEDA-3). We also evaluated changes in CD19+ B cell count, CD4+ and CD8+ T cell count, immunoglobulin titers, and occurrence of hypogammaglobulinemia (hypo-Ig). Frequency tests, multivariate regression models, and survival analysis were applied as appropriate. We analyzed data on 93 subjects (75.3% RRMS) for a total of 389 infusions (272 SID, 117 EID). Clinical and MRI activity, CDP, and NEDA 3 did not significantly differ between EID and SID. EID was associated with lower rates of B-cell depletion. T-cell dynamics and incidence of hypo-Ig were comparable following EID and SID. Hypo-IgG at index infusion was associated with further occurrence of hypo-IgG; male sex and hypo-IgM at index infusion were independently associated with hypo-IgM. In conclusion, OCR EID does not impact MS clinical and radiological outcomes, although it interferes with B-cell dynamics. These findings provide support for a tailored schedule of OCR in MS.
奥瑞珠单抗（OCR）是一种抗 CD20 单克隆抗体，已被批准用于治疗复发缓解型（RR）和原发性进展型（PP）多发性硬化症（MS）。标准间隔给药（SID）方案要求每 6 个月静脉输注一次。由于 COVID-19 大流行相关问题而延长给药间隔的经验表明，这种策略可能提供相当的疗效，同时减轻治疗负担和医疗保健成本。本研究旨在评估在真实环境中奥瑞珠单抗延长间隔给药（EID）的临床疗效、B 细胞和 T 细胞计数变化以及免疫球蛋白动态变化。我们回顾性纳入已接受 2 个 OCR 周期治疗的 RRMS 或 PPMS 患者，且末次输注后至少有 6 个月的随访。EID 定义为与 SID 相比延迟≥4 周。临床结局为复发、MRI 活动、6 个月确认的残疾进展（CDP）及其组合（无疾病活动证据，NEDA-3）。我们还评估了 CD19+B 细胞计数、CD4+和 CD8+T 细胞计数、免疫球蛋白滴度以及低丙种球蛋白血症（低 Ig）的发生变化。适当应用频率检验、多变量回归模型和生存分析。我们分析了 93 名受试者（75.3%为 RRMS）的 389 次输注（272 次 SID，117 次 EID）的数据。EID 和 SID 之间的临床和 MRI 活动、CDP 和 NEDA 3 无显著差异。EID 与 B 细胞耗竭率较低相关。EID 和 SID 后 T 细胞动力学和低 Ig 发生率相当。索引输注时的低 IgG 与进一步发生低 IgG 相关；索引输注时的男性和低 IgM 与低 IgM 独立相关。总之，OCR EID 不影响 MS 的临床和影像学结局，尽管它干扰了 B 细胞动力学。这些发现为 MS 中 OCR 的个体化治疗方案提供了支持。
