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接受生物技术和靶向免疫抑制剂治疗的慢性自身免疫性关节炎患者的结核病风险管理、筛查及预防性治疗

Management of tuberculosis risk, screening and preventive therapy in patients with chronic autoimmune arthritis undergoing biotechnological and targeted immunosuppressive agents.

作者信息

Picchianti-Diamanti Andrea, Aiello Alessandra, De Lorenzo Chiara, Migliori Giovanni Battista, Goletti Delia

机构信息

Department of Clinical and Molecular Medicine, "Sapienza" University, S. Andrea University Hospital, Rome, Italy.

Translational Research Unit, National Institute for Infectious Diseases "Lazzaro Spallanzani"- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.

出版信息

Front Immunol. 2025 Feb 3;16:1494283. doi: 10.3389/fimmu.2025.1494283. eCollection 2025.

Abstract

Tuberculosis (TB) is the leading cause of death in the world from an infectious disease. Its etiologic agent, the (Mtb), is a slow-growing bacterium that has coexisted in humans for thousands of years. According to the World Health Organization, 10.6 million new cases of TB and over 1 million deaths were reported in 2022. It is widely recognized that patients affected by chronic autoimmune arthritis such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) have an increased incidence rate of TB disease compared to the general population. As conceivable, the risk is associated with age ≥65 years and is higher in endemic regions, but immunosuppressive therapy plays a pivotal role. Several systematic reviews have analysed the impact of anti-TNF-α agents on the risk of TB in patients with chronic autoimmune arthritis, as well as for other biologic disease-modifying immunosuppressive anti-rheumatic drugs (bDMARDs) such as rituximab, abatacept, tocilizumab, ustekinumab, and secukinumab. However, the data are less robust compared to those available with TNF-α inhibitors. Conversely, data on anti-IL23 agents and JAK inhibitors (JAK-i), which have been more recently introduced for the treatment of RA and PsA/AS, are limited. TB screening and preventive therapy are recommended in Mtb-infected patients undergoing bDMARDs and targeted synthetic (ts)DMARDs. In this review, we evaluate the current evidence from randomized clinical trials, long-term extension studies, and real-life studies regarding the risk of TB in patients with RA, PsA, and AS treated with bDMARDs and tsDMARDs. According to the current evidence, TNF-α inhibitors carry the greatest risk of TB progression among bDMARDs and tsDMARDs, such as JAK inhibitors and anti-IL-6R agents. The management of TB screening and the updated preventive therapy are reported.

摘要

结核病(TB)是全球因传染病导致死亡的首要原因。其病原体结核分枝杆菌(Mtb)是一种生长缓慢的细菌,已在人类中存在了数千年。根据世界卫生组织的数据,2022年报告了1060万例新的结核病病例,死亡人数超过100万。人们普遍认识到,与普通人群相比,患有类风湿关节炎(RA)、银屑病关节炎(PsA)和强直性脊柱炎(AS)等慢性自身免疫性关节炎的患者结核病发病率有所增加。可以想象,这种风险与年龄≥65岁有关,在流行地区更高,但免疫抑制治疗起着关键作用。几项系统评价分析了抗TNF-α药物对慢性自身免疫性关节炎患者结核病风险的影响,以及对其他生物性疾病改善免疫抑制抗风湿药物(bDMARDs),如利妥昔单抗、阿巴西普、托珠单抗、乌司奴单抗和司库奇尤单抗的影响。然而,与TNF-α抑制剂相比,这些数据的可靠性较低。相反,最近用于治疗RA和PsA/AS的抗IL23药物和JAK抑制剂(JAK-i)的数据有限。对于接受bDMARDs和靶向合成(ts)DMARDs治疗的Mtb感染患者,建议进行结核病筛查和预防性治疗。在本综述中,我们评估了来自随机临床试验、长期扩展研究和真实世界研究的当前证据,这些证据涉及接受bDMARDs和tsDMARDs治疗的RA、PsA和AS患者的结核病风险。根据目前的证据,在bDMARDs和tsDMARDs中,如JAK抑制剂和抗IL-6R药物,TNF-α抑制剂导致结核病进展的风险最大。本文报告了结核病筛查的管理和最新的预防性治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c42/11830708/deff4dd78828/fimmu-16-1494283-g001.jpg

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