Background: The cerebellum is a functionally and anatomically complex structure, which, in multiple sclerosis (MS), is affected by focal white/gray matter lesions and by secondary neurodegeneration of afferent/efferent connections to the supratentorial brain and the spinal cord.

Objectives: To assess the efficacy of ocrelizumab compared with interferon β-1a (IFN β-1a)/placebo on cerebellar volume loss and the effect of switching to ocrelizumab on volume change in the Phase III trials in relapsing MS (RMS, OPERA I/II) and in primary progressive MS (PPMS, ORATORIO).

Methods: Cerebellar volume change was computed using paired Jacobian integration and analyzed using a mixed-effect repeated measurement model.

Results: In RMS, ocrelizumab reduced cerebellar volume loss in the double-blind period (DBP) and the difference (30% at DBP end) was maintained in the open-label extension (OLE) after control patients (IFN β-a) were switched to ocrelizumab. In PPMS, there was a small numerical difference in the DBP, but a larger (up to 22%) difference in favor of ocrelizumab in the OLE.

Conclusions: In both RMS and PPMS, early treatment with ocrelizumab helps to prevent additional cerebellar volume loss compared with delayed switching to ocrelizumab. Further analysis is needed to fully understand the clinical impact of cerebellar atrophy.

Keywords: Ocrelizumab; atrophy; cerebellum; multiple sclerosis; treatment outcome.

背景: 小脑是一个功能和结构上都非常复杂的组织，在多发性硬化症（MS）中，它会受到局部白质/灰质病变的影响，并且由于与小脑上方大脑和脊髓的传入/传出连接的继发性神经退行性疾病而受到影响。

目的: 评估奥瑞珠单抗与干扰素β-1a (IFN β-1a)/安慰剂相比对小脑体积损失的影响，并研究在III期试验中从干扰素β-1a转换为奥瑞珠单抗对复发性多发性硬化症（RMS，OPERA I/II）和原发进展型多发性硬化症（PPMS，ORATORIO）患者的小脑体积变化的影响。

方法: 使用配对雅可比积分法计算小脑体积的变化，并通过混合效应重复测量模型进行分析。

结果: 在RMS中，奥瑞珠单抗在双盲期(DBP)减少了小脑体积的损失，在开放标签扩展期(OLE)，对照组患者（IFN β-a）转换为奥瑞珠单抗后，差异（DBP结束时达30%）得以维持。在PPMS中，DBP期间存在一个微小的数值差异，但在OLE期间，奥瑞珠单抗的优势更为明显（最大达到22%）。

结论: 在RMS和PPMS患者中，早期使用奥瑞珠单抗有助于防止与延迟转换到奥瑞珠单抗相比的小脑体积进一步损失。需要进行更多的分析以全面理解小脑萎缩的临床影响。

关键词: 奥瑞珠单抗；萎缩；小脑；多发性硬化症；治疗结果。