Navigating the landscape of SLE treatment: An expert viewpoint on the rationality and limitations of early biologic intervention

IF 9.2 1区 医学 Q1 IMMUNOLOGY Autoimmunity reviews Pub Date : 2024-10-01 DOI:10.1016/j.autrev.2024.103612
Mariele Gatto , Margherita Zen , Claudio Cruciani , Luca Iaccarino , Andrea Doria
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Abstract

The approval of biologics, namely belimumab and anifrolumab, is being a game-changer in the approach to systemic lupus erythematosus (SLE). Currently we are indeed facing a revolution in the treatment paradigm of SLE, encompassing early combination of biologics with standard treatment in severe manifestations. In this regard, a lively discussion is taking place regarding the better positioning of biologics in the treatment of not necessarily severe, yet refractory and/or disfiguring manifestations which expose patients to worsened quality of life, reduced workability and enhanced risk of organ damage especially related to the misuse of glucocorticoids in the long run. Growing evidence supports the early use of targeted treatments in those patients, including the use of biologics before traditional immunosuppression, to achieve control of disease activity while minimizing treatment-related damage, privileging the timely use of therapeutics selectively impacting on key disease mechanisms in spite of a widespread immunosuppression. Patient profiling on a clinical and endotypical basis is helping in identifying better candidates to targeted drugs. More inflammatory organ involvement including persistent arthritis and infiltrating skin lesions seem likely to respond to anifrolumab, while B-mediated manifestations, a lively serology and a relapsing-remitting SLE course hint at a suitable role for belimumab. This seems at least partially connected to the inner effect of either drug, dampening inflammation through down-regulation of interferon signalling in the case of anifrolumab, while plastically modulating the B cell pool composition and function when coming to belimumab. Nevertheless, the mechanisms of both drugs are immunologically entangled at some extent, thereby requiring careful management especially in patients with longer disease history burdened with mixed manifestations. In this viewpoint we go over pros and cons of anticipatory biologic use in SLE, exploring features linked with better efficacy of either drug and the pathogenic and practical rationale for their positioning before traditional immunosuppression in moderate refractory SLE to be optimally managed in the 21st Century.
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系统性红斑狼疮治疗的导航:专家观点:早期生物干预的合理性和局限性。
生物制剂(即贝利木单抗和阿尼夫单抗)的批准改变了系统性红斑狼疮(SLE)的治疗方法。目前,我们确实正面临着系统性红斑狼疮治疗模式的一场革命,其中包括生物制剂与标准治疗的早期联合应用。在这方面,人们正在热烈讨论生物制剂在治疗不一定严重、但难治性和/或毁容性表现方面的更佳定位,这些表现使患者的生活质量恶化、工作能力下降,器官损伤的风险增加,特别是与长期滥用糖皮质激素有关。越来越多的证据支持对这些患者及早使用靶向治疗,包括在传统免疫抑制之前使用生物制剂,以控制疾病活动,同时最大限度地减少与治疗相关的损害。以临床和内型为基础的患者特征描述有助于确定更好的靶向药物候选者。包括持续性关节炎和皮肤浸润性病变在内的更多炎症器官受累似乎可能对安非罗单抗产生反应,而B介导的表现、活跃的血清学和复发-缓解型系统性红斑狼疮病程则暗示着贝利木单抗的合适作用。这似乎至少部分与这两种药物的内在作用有关:安非罗单抗通过下调干扰素信号抑制炎症,而贝利木单抗则可塑地调节B细胞池的组成和功能。然而,这两种药物的机制在一定程度上存在免疫学上的纠结,因此需要谨慎管理,尤其是对于病史较长、有混合表现的患者。在这篇文章中,我们将阐述在系统性红斑狼疮中使用预期生物制剂的利弊,探讨与这两种药物更好的疗效相关的特征,以及在中度难治性系统性红斑狼疮中将其置于传统免疫抑制之前的病理和实际理由,以便在21世纪对其进行优化管理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Autoimmunity reviews
Autoimmunity reviews 医学-免疫学
CiteScore
24.70
自引率
4.40%
发文量
164
审稿时长
21 days
期刊介绍: Autoimmunity Reviews is a publication that features up-to-date, structured reviews on various topics in the field of autoimmunity. These reviews are written by renowned experts and include demonstrative illustrations and tables. Each article will have a clear "take-home" message for readers. The selection of articles is primarily done by the Editors-in-Chief, based on recommendations from the international Editorial Board. The topics covered in the articles span all areas of autoimmunology, aiming to bridge the gap between basic and clinical sciences. In terms of content, the contributions in basic sciences delve into the pathophysiology and mechanisms of autoimmune disorders, as well as genomics and proteomics. On the other hand, clinical contributions focus on diseases related to autoimmunity, novel therapies, and clinical associations. Autoimmunity Reviews is internationally recognized, and its articles are indexed and abstracted in prestigious databases such as PubMed/Medline, Science Citation Index Expanded, Biosciences Information Services, and Chemical Abstracts.
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