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监测重症肌无力患者体内的抗利妥昔单抗抗体对利妥昔单抗治疗期间的事件发生时间有影响。

Monitoring anti-Rituximab antibodies in myasthenia gravis affects the time to event during Rituximab treatment.

作者信息

Héraud Charlotte, Bresch Saskia, Bourg Véronique, Landes-Château Cassandre, Ruetsch-Chelli Caroline, Ticchioni Michel, Seitz-Polski Barbara, Lebrun-Frenay Christine

机构信息

CRC-SEP, Service de Neurologie, Hôpital Pasteur 2, CHU de Nice, Université Côte d'Azur, 30 Voie Romaine, 06200, Nice, France.

Unité de Recherche Clinique de la Côte d'Azur (UR2 CA-URRIS), Université Côte d'Azur, Nice, France.

出版信息

J Neurol. 2025 Jun 9;272(7):451. doi: 10.1007/s00415-025-13161-6.

Abstract

INTRODUCTION

Rituximab (RTX) effectively manages myasthenia gravis (MG) by reducing relapse rates. Anti-Rituximab antibodies can develop in autoimmune diseases and may lead to RTX resistance. Although RTX infusions are increased, these antibodies do not influence the occurrence of adverse events. We conducted a retrospective study to evaluate how anti-drug antibodies (ADAs) impact treatment efficacy.

METHODS

We reviewed 101 MG patients treated with first- or second-line RTX at Nice University Hospital from 2016 to 2023. Clinical assessments were performed quarterly using the Osserman Score (OS). Biological tests included ADA levels, RTX serum levels, CD19+CD27+ memory B cells, and CD19+ cell counts.

RESULTS

Among 101 patients, 38 developed ADAs (37.6%), with a median onset of 433.5 days after the first infusion. The ADA group had significantly more RTX infusions (6.18 vs. 4.29, p=0.002) and more prolonged treatment durations (1908.26 vs. 1441.3 days, p=0.006). No differences in age, gender, or prior immunosuppression were noted. OS scores revealed no significant difference between ADA-positive and ADA-negative patients. The interval between infusions remained consistent before and after the appearance of ADAs.

DISCUSSION

ADAs were found in one-third of MG patients treated with RTX, a higher prevalence than in other conditions. The number of RTX infusions was significantly greater in the ADA-positive group, and the longer is the treatment duration, the higher the likelihood of developing ADAs. Our findings suggest a need to reconsider routine ADA testing, as it does not correlate with clinical outcomes or infusion intervals. This raises questions about how to tailor maintenance therapy for MG patients stabilized with RTX.

摘要

引言

利妥昔单抗(RTX)通过降低复发率有效治疗重症肌无力(MG)。抗利妥昔单抗抗体可在自身免疫性疾病中产生,并可能导致RTX耐药。尽管增加了RTX输注量,但这些抗体并不影响不良事件的发生。我们进行了一项回顾性研究,以评估抗药物抗体(ADA)如何影响治疗效果。

方法

我们回顾了2016年至2023年在尼斯大学医院接受一线或二线RTX治疗的101例MG患者。每季度使用 Osserman评分(OS)进行临床评估。生物学检测包括ADA水平、RTX血清水平、CD19 + CD27 + 记忆B细胞和CD19 + 细胞计数。

结果

101例患者中,38例产生了ADA(37.6%),首次输注后中位发病时间为433.5天。ADA组的RTX输注次数明显更多(6.18次对4.29次,p = 0.002),治疗持续时间更长(1908.26天对1441.3天,p = 0.006)。在年龄、性别或既往免疫抑制方面未发现差异。OS评分显示ADA阳性和ADA阴性患者之间无显著差异。ADA出现前后输注间隔保持一致。

讨论

在接受RTX治疗的MG患者中,三分之一发现了ADA,其患病率高于其他疾病。ADA阳性组的RTX输注次数明显更多,治疗持续时间越长,产生ADA的可能性越高。我们的研究结果表明需要重新考虑常规ADA检测,因为它与临床结果或输注间隔无关。这就引发了关于如何为使用RTX病情稳定的MG患者定制维持治疗的问题。

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