BACKGROUND Phase II and observational studies support the use of rituximab in multiple sclerosis. Standard protocols are lacking, but studies suggest comparable efficacy between low- and high-dose regimens. OBJECTIVE To evaluate effectiveness and safety of de-escalating rituximab dose from 1000 to 500 mg/6 months in multiple sclerosis. METHODS Patients were switched from rituximab 1000 to 500 mg/6 months and prospectively followed for 12 months. Relapses, disability, occurrence of brain/spinal magnetic resonance imaging (MRI) lesions, serum neurofilament light chain (NfL), CD19+ B cell, and IgG concentrations were analyzed. RESULTS Fifty-nine patients were included (37 relapsing-remitting, 22 secondary progressive). No relapses occurred, with no difference in expanded disability status scale (EDSS) between baseline (4 (2.5-4.5) and 12 months (3.5 (2.5-5.5) p = 0.284). Overall, three new T2 lesions appeared during follow-up. NfL concentration was stable between baseline (7.9 (5.9-45.2) pg/mL) and 12 months (9.1 (5.9-21.3) pg/mL, p = 0.120). IgG concentrations decreased with greater rituximab load (coefficient = -0.439, p = 0.041). IgG deficient patients had greater risk of infections (OR = 6.27, 95% CI = 1.71-22.9, p = 0.005). CONCLUSION De-escalating rituximab dose from 1000 to 500 mg/6 months is safe, results in clinical and radiological stability, and does not affect serum NfL over 12 months. Rituximab load negatively influences IgG concentrations, and IgG deficient patients are at higher risk of infections.

中文翻译：

---

降低利妥昔单抗剂量导致多发性硬化症的临床、放射学和血清神经丝水平的稳定性

背景 II 期和观察性研究支持在多发性硬化症中使用利妥昔单抗。缺乏标准方案，但研究表明低剂量和高剂量方案之间的疗效相当。目的 评估将利妥昔单抗剂量从 1000 毫克/6 个月递减至 500 毫克/6 个月治疗多发性硬化症的有效性和安全性。方法 患者从 rituximab 1000 改为 500 mg/6 个月，并前瞻性随访 12 个月。分析了复发、残疾、脑/脊髓磁共振成像 (MRI) 病变的发生、血清神经丝轻链 (NfL)、CD19+ B 细胞和 IgG 浓度。结果 共纳入 59 名患者（37 名复发-缓解，22 名继发性进展）。没有复发，基线（4 (2.5-4.5) 和 12 个月 (3. 5 (2.5-5.5) p = 0.284)。总体而言，随访期间出现了三个新的 T2 病变。NfL 浓度在基线 (7.9 (5.9-45.2) pg/mL) 和 12 个月 (9.1 (5.9-21.3) pg/mL，p = 0.120) 之间保持稳定。IgG 浓度随着利妥昔单抗负载量的增加而降低（系数 = -0.439，p = 0.041）。IgG 缺陷患者感染风险更高（OR = 6.27，95% CI = 1.71-22.9，p = 0.005）。结论 将利妥昔单抗的剂量从 1000 毫克/6 个月递减至 500 毫克/6 个月是安全的，导致临床和放射学稳定性，并且在 12 个月内不会影响血清 NfL。利妥昔单抗负荷对 IgG 浓度产生负面影响，并且 IgG 缺陷患者感染的风险更高。3) pg/mL，p = 0.120)。IgG 浓度随着利妥昔单抗负载量的增加而降低（系数 = -0.439，p = 0.041）。IgG 缺陷患者感染风险更高（OR = 6.27，95% CI = 1.71-22.9，p = 0.005）。结论 将利妥昔单抗的剂量从 1000 毫克/6 个月递减至 500 毫克/6 个月是安全的，导致临床和放射学稳定性，并且在 12 个月内不会影响血清 NfL。利妥昔单抗负荷对 IgG 浓度产生负面影响，并且 IgG 缺陷患者感染的风险更高。3) pg/mL，p = 0.120)。IgG 浓度随着利妥昔单抗负载量的增加而降低（系数 = -0.439，p = 0.041）。IgG 缺陷患者感染风险更高（OR = 6.27，95% CI = 1.71-22.9，p = 0.005）。结论 将利妥昔单抗的剂量从 1000 毫克/6 个月递减至 500 毫克/6 个月是安全的，导致临床和放射学稳定性，并且在 12 个月内不会影响血清 NfL。利妥昔单抗负荷对 IgG 浓度产生负面影响，并且 IgG 缺陷患者感染的风险更高。并且在 12 个月内不会影响血清 NfL。利妥昔单抗负荷对 IgG 浓度产生负面影响，而 IgG 缺陷患者感染的风险更高。并且在 12 个月内不会影响血清 NfL。利妥昔单抗负荷对 IgG 浓度产生负面影响，并且 IgG 缺陷患者感染的风险更高。