Objectives

To evaluate the effect of intrathecally (IT) delivered rituximab as a therapeutic intervention for progressive multiple sclerosis (PMS) during a 3-year follow-up period.

Methods

Participants of a 1-year open-label phase 1b study of IT delivered rituximab to patients with PMS were offered extended treatment with follow-up for an additional 2 years. During the extension phase, treatment with 25 mg rituximab was administered every 6 months via a subcutaneous Ommaya reservoir connected to the right frontal horn with a ventricular catheter.

Results

Mild to moderate vertigo and nausea occurred in 4 out of 14 participants as temporary adverse events associated with IT rituximab infusion. During the entire 3-year period, two cases of low-virulent bacterial meningitis occurred, which were successfully treated. Walking speed deteriorated significantly during the study.

Conclusions

IT administration of rituximab via a ventricular catheter was well tolerated. Considering the meningitis cases, the risk of infection was not negligible. The continued loss of walking speed indicates that IT rituximab was not able to stop disease progression.

Classification of evidence

This study provides class IV evidence that intraventricularly administered rituximab in progressive MS is associated with a risk for bacterial meningitis and does not halt disease progression.

EU Clinical Trial Register

EudraCT; 2008-002626-11 and 2012-000721-53

中文翻译：

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利妥昔单抗在进行性 MS 中的鞘内治疗试验：延长 2 年后的结果。

目标

在 3 年的随访期内，评估鞘内 (IT) 递送利妥昔单抗作为进行性多发性硬化症 (PMS) 治疗干预的效果。

方法

一项为期 1 年的开放标签 1b 期 IT 研究的参与者向 PMS 患者提供了利妥昔单抗，并获得了延长治疗和额外 2 年的随访。在扩展阶段，每 6 个月通过皮下 Ommaya 贮液器给予 25 mg 利妥昔单抗治疗，该贮液器通过心室导管与右额角相连。

结果

14 名参与者中有 4 名出现轻度至中度眩晕和恶心，这是与 IT 利妥昔单抗输注相关的暂时性不良事件。整个3年期间，发生2例低毒力细菌性脑膜炎，均成功治疗。研究期间步行速度显着下降。

结论

通过心室导管 IT 给药的利妥昔单抗耐受性良好。考虑到脑膜炎病例，感染的风险不容忽视。步行速度的持续下降表明 IT 利妥昔单抗无法阻止疾病进展。

证据分类

这项研究提供了 IV 类证据，表明在进行性 MS 中脑室内给予利妥昔单抗与细菌性脑膜炎的风险相关，并且不会阻止疾病进展。

欧盟临床试验注册

EudraCT; 2008-002626-11 和 2012-000721-53