系统性红斑狼疮中的生物制剂：近期进展与益处

Biologics in Systemic Lupus Erythematosus: Recent Evolutions and Benefits.

作者信息

Kundnani Nilima Rajpal, Levai Mihaela Codrina, Popa Mihaela-Diana, Borza Claudia, Iacob Mihai, Mederle Alexandra Laura, Blidisel Alexandru

机构信息

Department of Cardiology-Internal Medicine and Ambulatory Care, Prevention and Cardiovascular Recovery, "Victor Babeș" University of Medicine and Pharmacy, 300041 Timisoara, Romania.

Research Centre of Timișoara Institute of Cardiovascular Diseases, "Victor Babeș" University of Medicine and Pharmacy, 300041 Timisoara, Romania.

出版信息

Pharmaceutics. 2024 Sep 6;16(9):1176. doi: 10.3390/pharmaceutics16091176.

DOI:10.3390/pharmaceutics16091176

PMID:39339212

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11434659/

Abstract

INTRODUCTION

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by significant autoantibodies, particularly targeting nuclear antigens. SLE pathogenesis involves genetic, environmental, and hormonal factors. The disease course includes flares and remission and involves various organs. Recent therapeutic progresses, including biologics, have improved management and prognosis, though the long-term impact of novel therapies remains to be determined. Biologics in SLE: Rituximab, the earliest B-cell-oriented biologic, binds CD20 and depletes CD20+ B cells, leading to remission in some SLE patients. Belimumab is a B-cell-activating factor (BAFF) inhibitor with a recent additional indication for lupus nephritis. The CALIBRATE and BLISS-BELIEVE studies investigated combinations of these drugs with conventional therapies, showing varied efficacy. Ocrelizumab and obinutuzumab, newer CD20-oriented SLE therapies, together with ofatumumab and veltuzumab, are also promising. The latest trials highlight their efficacy and safety. Anifrolumab, targeting type-I interferon receptors, was evaluated in the TULIP 1/2 trials. The ongoing TULIP LTE trial supports the long-term safety and efficacy of anifrolumab. Additionally, the IRIS Phase III trial is exploring anifrolumab for lupus nephritis, showing favorable renal responses. Tocilizumab and secukinumab are being assessed for SLE, with mixed outcomes. Several biologics targeting the C5 complement protein, together with immunomodulators and immunotherapeutics, are also under investigation for potential benefits in SLE.

DISCUSSION

Biologics in SLE target specific immune components, aiming to improve disease control and reduce the side effects of conventional therapy. However, trial outcomes vary due to factors like inclusion criteria and trial design.

CONCLUSIONS

Biotechnology progress enables targeted biologic therapies for SLE, reducing disease activity and improving patients' quality of life.

摘要

引言

系统性红斑狼疮（SLE）是一种多方面的自身免疫性疾病，其特征是存在大量自身抗体，尤其是针对核抗原的抗体。SLE的发病机制涉及遗传、环境和激素因素。疾病过程包括病情发作和缓解，并累及多个器官。尽管新型疗法的长期影响仍有待确定，但包括生物制剂在内的近期治疗进展改善了疾病管理和预后。SLE中的生物制剂：利妥昔单抗是最早的靶向B细胞的生物制剂，它结合CD20并消耗CD20+B细胞，使一些SLE患者病情缓解。贝利尤单抗是一种B细胞激活因子（BAFF）抑制剂，最近增加了狼疮性肾炎的适应证。CALIBRATE和BLISS - BELIEVE研究调查了这些药物与传统疗法的联合应用，显示出不同的疗效。奥瑞珠单抗和奥妥珠单抗是较新的靶向CD20的SLE疗法，与奥法木单抗和维妥珠单抗一样，也很有前景。最新试验突出了它们的疗效和安全性。阿尼鲁单抗靶向I型干扰素受体，在TULIP 1/2试验中进行了评估。正在进行的TULIP LTE试验支持阿尼鲁单抗的长期安全性和疗效。此外，IRIS III期试验正在探索阿尼鲁单抗用于狼疮性肾炎的治疗，显示出良好的肾脏反应。托珠单抗和司库奇尤单抗正在接受SLE评估，结果不一。几种靶向C5补体蛋白的生物制剂，以及免疫调节剂和免疫治疗药物，也正在研究其在SLE中的潜在益处。