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布鲁顿酪氨酸激酶抑制剂:它们能否被优化用于治疗神经炎症性疾病?

Bruton tyrosine kinase inhibitors: can they be optimized for the treatment of neuroinflammatory disorders?

机构信息

Neurology Unit, Department of Neurosciences, University of Padova, Padua, Italy.

Hematology Unit, Department of Medicine, University of Padova, Padua, Italy.

出版信息

Expert Opin Investig Drugs. 2023 Jul-Dec;32(12):1105-1111. doi: 10.1080/13543784.2023.2288076. Epub 2023 Dec 28.

Abstract

INTRODUCTION

Bruton's tyrosine kinase (BTK) is a multifaceted player of the immune system which has been involved in the survival of hematological malignancies but also in the pathogenesis of immune-mediated diseases. Oral BTK inhibitors (BTKi) have become a cornerstone for the treatment of patients with B-cell malignancies, and are under investigation for several immune-mediated diseases.

AREAS COVERED

We reviewed the biology of BTK and emerging data on BTKi in patients with neuroinflammatory disorders of both the peripheral and central nervous system.

EXPERT OPINION

We support the use of BTKi in relapsed/refractory patients with multiple sclerosis and anti-MAG antibody neuropathies. However, other immune-mediated neuroinflammatory disorders are likely to benefit from BTKi. Whether BTKi will improve the response rates than conventional therapies in previously untreated patients is unknown and will be assessed within future clinical trials. Furthermore, the availability of more selective BTKi, with less adverse events, will improve patients' tolerability and expand our treatment landscape.

摘要

简介

布鲁顿酪氨酸激酶(BTK)是免疫系统的多面手,它不仅参与了血液系统恶性肿瘤的存活,也参与了免疫介导性疾病的发病机制。口服 BTK 抑制剂(BTKi)已成为治疗 B 细胞恶性肿瘤患者的基石,并正在针对多种免疫介导性疾病进行研究。

涵盖领域

我们回顾了 BTK 的生物学特性以及 BTKi 在周围和中枢神经系统神经炎症性疾病患者中的最新数据。

专家意见

我们支持在复发/难治性多发性硬化症和抗 MAG 抗体神经病患者中使用 BTKi。然而,其他免疫介导的神经炎症性疾病可能也会从 BTKi 中获益。BTKi 是否会比传统疗法在未经治疗的患者中提高应答率尚不清楚,这将在未来的临床试验中进行评估。此外,具有更少不良反应的更具选择性的 BTKi 将提高患者的耐受性并扩大我们的治疗范围。

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