B 淋巴细胞指导下的补救治疗有助于在接受利妥昔单抗治疗的 MS 患者中建立良好的疗效和安全性特征。

B-lymphocyte-guided retreatment contributes to establish good effectiveness and safety profile in MS patients treated with rituximab.

机构信息

Multiple Sclerosis Unit, Department of Neurology, Hospital Universitario Ramón y Cajal, IRYCIS, M-607, 9, 100, Madrid 28034, Spain.

出版信息

Mult Scler Relat Disord. 2022 Dec;68:104218. doi: 10.1016/j.msard.2022.104218. Epub 2022 Oct 8.

DOI:10.1016/j.msard.2022.104218

PMID:36270253

Abstract

BACKGROUND

Rituximab is extensively used for multiple sclerosis (MS) treatment. However, the best dosage remains to be established. It has been proposed that retreatment could be guided by B lymphocyte (BL) percentages.

OBJECTIVE

To establish the best BL value for retreatment with rituximab in MS and to confirm the safety and efficacy of this approach.

METHODS

A prospective study was done with an exploratory cohort and a confirmatory cohort of MS patients treated with rituximab between 2017 and 2021. The first one comprised 10 MS patients with BL assessed every 3 months after rituximab infusion and retreatment done when BL values were ≥0.5%. The confirmatory cohort included 41 MS patients (41.5% women, 87.8% with secondary progressive MS, median age = 46.3 (interquartile range: 41.3-52.1) years, disease duration = 14.1 (9-19.6) years, EDSS score = 5.5 (4.0-6.5)). The confirmatory cohort was treated with rituximab following the pattern established in the exploratory cohort.

RESULTS

In the exploratory cohort, ≥0.2% BL was established as the best value for retreatment because in most cases, a substantial increase of BL counts was preceded by initial values of 0.2-0.3%. In the confirmatory cohort, rituximab reduced the annualized relapse rate (ARR 0.56 vs. 0.125, p < 0.001), proportion of patients with appearance of new/enlarged T2 lesions (63.4% vs. 12.2%, p < 0.001), gadolinium-enhancing lesions (39% vs. 0%, p < 0.001), and confirmed disability progression (55% vs. 27.5%, p = 0.037). There were 22 patients (53.7%) who achieved NEDA-3. No patients had severe infections, and 10.7% cases had reduced IgG levels.

CONCLUSION

Rituximab treatment guided by BL showed high effectiveness and a good safety profile for MS patients after one year of treatment.

摘要

背景

利妥昔单抗广泛用于多发性硬化症（MS）的治疗。然而，最佳剂量仍有待确定。有人提出，再治疗可以通过 B 淋巴细胞（BL）百分比来指导。

目的

确定 MS 患者接受利妥昔单抗再治疗的最佳 BL 值，并确认这种方法的安全性和有效性。

方法

对 2017 年至 2021 年期间接受利妥昔单抗治疗的 MS 患者进行了一项前瞻性研究，包括一个探索性队列和一个验证性队列。第一个队列包括 10 名 BL 每 3 个月评估一次的 MS 患者，在 BL 值≥0.5%时进行再治疗。验证性队列包括 41 名 MS 患者（41.5%为女性，87.8%为继发进展性 MS，中位年龄 46.3（四分位距：41.3-52.1）岁，病程 14.1（9-19.6）年，EDSS 评分为 5.5（4.0-6.5））。验证性队列按照探索性队列中建立的模式接受利妥昔单抗治疗。

结果

在探索性队列中，确定 BL≥0.2%为再治疗的最佳值，因为在大多数情况下，BL 计数的显著增加之前，初始值为 0.2-0.3%。在验证性队列中，利妥昔单抗降低了年复发率（ARR 0.56 与 0.125，p<0.001），出现新/扩大 T2 病变的患者比例（63.4%与 12.2%，p<0.001），钆增强病变（39%与 0%，p<0.001）和确诊的残疾进展（55%与 27.5%，p=0.037）。有 22 名患者（53.7%）达到了 NEDA-3。没有患者发生严重感染，10.7%的患者出现 IgG 水平降低。