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马伏鲁单抗:类风湿关节炎治疗现状的独特见解和更新。

Mavrilimumab: a unique insight and update on the current status in the treatment of rheumatoid arthritis.

机构信息

a Department of Rheumatology , Gaetano Pini Institute , Milan , Italy.

b Department of Clinical Sciences and Health Community , University of Milan, Division of Rheumatology, Gaetano Pini Institute , Milan , Italy.

出版信息

Expert Opin Investig Drugs. 2019 Jul;28(7):573-581. doi: 10.1080/13543784.2019.1631795. Epub 2019 Jun 17.

Abstract

: Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease, which affects joints and extra-articular structures. Nowadays, the armamentarium of therapeutic options is progressively expanding and embraces several mechanisms of action: TNF inhibition, B-cell depletion, T-cell co-stimulation inhibition, IL-6 blockade, and JAK-inhibition. Granulocyte-Monocyte-Colony-Stimulating-Factor (GM-CSF) is a mediator acting as a cytokine with a proven pathogenetic role in RA, providing a potential alternative target for the management of the disease. Mavrilimumab is a monoclonal antibody against GM-CSF receptor, which has been successfully tested in RA patients. : Beginning with a description of the preclinical evidence and the rationale for GM-CSF blockade in RA, this review will provide a wide overview of mavrilimumab efficacy and safety profile by analyzing phase I/II RCTs conducted in patients with moderate to severe RA. : According to the promising results from phase I-II RCTs, mavrilimumab could be considered as an additional therapeutic option for RA patients multi-resistant to the available targeted drugs. However, the optimal dose and the profile of this new drug should be confirmed in phase III RCTs before the marketing.

摘要

类风湿关节炎(RA)是一种慢性、系统性、自身免疫性疾病,影响关节和关节外结构。如今,治疗选择的武器库正在不断扩大,包括几种作用机制:TNF 抑制、B 细胞耗竭、T 细胞共刺激抑制、IL-6 阻断和 JAK 抑制。粒细胞-单核细胞集落刺激因子(GM-CSF)是一种细胞因子介质,在 RA 中具有已被证实的发病机制作用,为疾病的治疗提供了一个潜在的替代靶点。Mavrilimumab 是一种针对 GM-CSF 受体的单克隆抗体,已在 RA 患者中成功进行了测试。:本文从 GM-CSF 阻断在 RA 中的临床前证据和原理描述开始,通过分析在中度至重度 RA 患者中进行的 I/II 期 RCT,全面概述 mavrilimumab 的疗效和安全性概况。:根据 I/II 期 RCT 的有希望的结果,mavrilimumab 可以被认为是对现有靶向药物耐药的 RA 患者的另一种治疗选择。然而,在上市之前,应在 III 期 RCT 中确认这种新药的最佳剂量和特征。

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