Revie Lisa, Jürjens Annika, Eveslage Maria, Trümpelmann Susan, Teschner Valerie, Schulte-Mecklenbeck Andreas, Gross Catharina C, Lünemann Jan D, Grosch Jan, Korsukewitz Catharina, Wiendl Heinz, Klotz Luisa
Department of Neurology With Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.
Mult Scler. 2025 Jun;31(7):813-820. doi: 10.1177/13524585251329849. Epub 2025 Apr 3.
While treatment with ocrelizumab has proven effective in preventing relapse-associated worsening (RAW) in relapsing multiple sclerosis (RMS), a significant number of patients experience progression independent of relapse activity (PIRA).
To investigate the association between B-cell depletion status and the risk of disability accumulation in RMS patients receiving ocrelizumab treatment.
In this monocentric cohort study of 148 RMS patients (2017-2023), we categorized participants into three groups: no evidence of disease activity (NEDA), evidence of disease activity (EDA), and PIRA. B-cell counts were measured every 6-12 months, with suboptimal depletion defined as ⩾10 CD19+ B-cells/µL. Logistic regression and Cox proportional hazards models analyzed the relationship between B-cell depletion and disability progression.
Of 148 patients, 70 (47%) achieved NEDA, 51 (34%) showed EDA, and 25 (17%) developed PIRA. NEDA patients demonstrated significantly lower B-cell counts compared to EDA ( < 0.01) and PIRA ( < 0.001) groups. Insufficient B-cell depletion was the strongest PIRA predictor (OR 3.73, 95% CI: 2.50-5.43, < 0.001) and increased EDSS progression risk (HR 0.50, 95% CI: 0.26-0.97, = 0.039).
PIRA occurs in the context of suboptimal B-cell depletion in RMS patients, highlighting the need for close monitoring and potential adjustment of infusion intervals.
虽然奥瑞珠单抗治疗已被证明可有效预防复发型多发性硬化症（RMS）中与复发相关的病情恶化（RAW），但仍有相当数量的患者出现与复发活动无关的病情进展（PIRA）。
研究接受奥瑞珠单抗治疗的RMS患者的B细胞耗竭状态与残疾累积风险之间的关联。
在这项对148例RMS患者（2017 - 2023年）进行的单中心队列研究中，我们将参与者分为三组：无疾病活动证据（NEDA）、有疾病活动证据（EDA）和PIRA。每6 - 12个月测量一次B细胞计数，次优耗竭定义为≥10个CD19 + B细胞/μL。采用逻辑回归和Cox比例风险模型分析B细胞耗竭与残疾进展之间的关系。
148例患者中，70例（47%）达到NEDA，51例（34%）表现为EDA，25例（17%）出现PIRA。与EDA组（P < 0.01）和PIRA组（P < 0.001）相比，NEDA患者的B细胞计数显著更低。B细胞耗竭不足是最强的PIRA预测因素（OR 3.73，95% CI：2.50 - 5.43，P < 0.001），并增加了扩展残疾状态量表（EDSS）进展风险（HR 0.50，95% CI：0.26 - 0.97，P = 0.039）。
RMS患者中PIRA发生在B细胞耗竭次优的情况下，这突出了密切监测和潜在调整输注间隔的必要性。
