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Rheumatoid arthritis: prediction of future clinically-apparent disease, and prevention. 类风湿性关节炎:未来临床显现疾病的预测和预防。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-05 DOI: 10.1097/BOR.0000000000001013
Kevin D Deane

Purpose of review: This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA).

Recent findings: In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a 'simple' score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA.

Summary: Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.

综述的目的:本综述讨论了预测和预防未来类风湿性关节炎(RA)的最新进展:在有肌肉骨骼症状和瓜氨酸蛋白抗体(ACPA)升高但无临床炎症性关节炎(IA)的个体中,"简单 "评分对1年内临床IA/RA的阳性预测值(PPV)为28%,综合评分(包括超声波)对5年内临床RA的阳性预测值(PPV)为71%。对未来可能患上 RA 的高危人群进行了对照临床试验,使用了皮质类固醇、利妥昔单抗、阿托伐他汀、甲氨蝶呤、羟氯喹和阿帕他赛。在试验中,阿巴他赛普适度降低了临床 RA 病发率和影像学炎症,利妥昔单抗推迟了临床 IA,而甲氨蝶呤改善了功能、症状和影像学炎症。含有或不含有欧米伽 3 脂肪酸的维生素 D 可降低包括 RA 在内的自身免疫性疾病的发病率。小结:尽管目前还没有获得批准的预防干预措施,但 RA 的预测和预防工作正在取得进展。未来的研究应包括对RA发展的病理生理学进行更深入的评估,以提高预测能力,确定未来临床试验的目标关键途径,以及开发支持预防相关研究的基础设施。
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引用次数: 0
Management of postinfectious inflammatory arthritis. 感染后炎症性关节炎的治疗。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-02-21 DOI: 10.1097/BOR.0000000000001009
Hailey Baker, J Kennedy Amaral, Robert T Schoen

Purpose of review: Postinfectious inflammatory arthritis can result from various pathogens, including bacteria, viruses, fungi, and parasites. Prompt identification and treatment of acute infection is vital, but some cases progress to chronic arthritis despite successful treatment of infection. Postinfectious inflammatory arthritis varies from mild, self-limited arthralgia to severe, refractory arthritis, necessitating ongoing disease-modifying treatment. This review explores the spectrum of postinfectious inflammatory arthritis to provide insights into effective management.

Recent findings: Research continues regarding the benefit of antimicrobial therapy, beyond treatment of the acute infection, to diminish the severity of postinfectious inflammatory arthritis. Following treatment of acute infection, most cases are self-limited so treatment is symptomatic. However, a difficult-to-predict fraction of cases develop chronic postinfectious inflammatory arthritis that can be challenging to manage. Recently, as more biologic, and targeted synthetic DMARDs have become available, treatment options have expanded.

Summary: In this article, we use the term 'postinfectious inflammatory arthritis' rather than 'reactive arthritis' because it describes a broader spectrum of diseases and emphasizes the common pathogenesis of a postinfectious inflammatory process. We summarize the conventional therapies and recent management developments for the most frequently encountered postinfectious inflammatory arthritides.

审查目的:感染后炎性关节炎可由各种病原体引起,包括细菌、病毒、真菌和寄生虫。及时发现和治疗急性感染至关重要,但有些病例尽管成功治疗了感染,却发展为慢性关节炎。感染后炎症性关节炎从轻微的自限性关节痛到严重的难治性关节炎不等,需要持续的疾病调整治疗。这篇综述探讨了感染后炎症性关节炎的范围,为有效治疗提供了见解:除治疗急性感染外,有关抗菌治疗对减轻感染后炎症性关节炎严重程度的益处的研究仍在继续。在治疗急性感染后,大多数病例都会自愈,因此只需对症治疗。然而,有一部分病例会发展为慢性感染后炎症性关节炎,其治疗难度难以预测。摘要:在本文中,我们使用 "感染后炎症性关节炎 "而不是 "反应性关节炎",因为它描述的疾病范围更广,并强调了感染后炎症过程的共同发病机制。我们总结了最常见的感染后炎症性关节炎的传统疗法和最新治疗进展。
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引用次数: 0
Updates on interstitial lung disease and other selected extra-articular manifestations of rheumatoid arthritis. 类风湿关节炎间质性肺病及其他部分关节外表现的最新进展。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-02-23 DOI: 10.1097/BOR.0000000000001007
Elena Myasoedova, Eric L Matteson

Purpose of review: To discuss changes in epidemiology, recent advances in understanding of the pathogenesis and management of selected extraarticular manifestations of rheumatoid arthritis (ExRA).

Recent findings: The incidence of ExRA overall and subcutaneous rheumatoid nodules in particular is declining after 2000. These trends reflect improved RA disease activity with early effective immunosuppressive treatments; changing environmental risk factors can be contributing. ExRA continues to carry a two-fold increased mortality risk. RA-associated interstitial lung disease (RA-ILD) is a major contributor to mortality, with no decline in incidence and scant therapeutic options. Individualized risk stratification for RA-ILD based on patient-level risk factors and biomarker profile is evolving with MUC5B as a major genetic risk factor. Clinical trials are underway to evaluate the benefits of novel antifibrotic therapies and targeted therapies for RA-ILD. The risk of cardiovascular disease in RA is generally amendable to treatment with disease-modifying antirheumatic drugs, although cardiovascular risk associated with JAK inhibition is not fully understood.

Summary: Despite reduction in incidence of ExRA overall, the incidence of RA-ILD shows no significant decline and remains a major therapeutic challenge. The use of novel antifibrotics and immunosuppressive drugs shows promise in slowing the progression of RA-ILD.

综述的目的:讨论流行病学的变化、对类风湿关节炎(ExRA)部分关节外表现的发病机制和管理的最新进展:最近的研究结果:2000年后,类风湿关节炎(ExRA)的总体发病率,尤其是皮下类风湿结节的发病率正在下降。这些趋势反映出随着早期有效的免疫抑制治疗,类风湿关节炎的疾病活动性有所改善;环境风险因素的变化也可能是原因之一。类风湿关节炎的死亡风险继续增加两倍。RA相关性间质性肺病(RA-ILD)是导致死亡的主要因素,发病率没有下降,治疗方案也很少。根据患者的风险因素和生物标志物特征对RA-ILD进行个体化风险分层,MUC5B是一个主要的遗传风险因素。目前正在进行临床试验,以评估新型抗纤维化疗法和靶向疗法对RA-ILD的益处。RA的心血管疾病风险一般可通过使用改变病情的抗风湿药物进行治疗,但与JAK抑制剂相关的心血管疾病风险尚未完全明了。摘要:尽管ExRA的总体发病率有所下降,但RA-ILD的发病率并未显著下降,仍是一项重大的治疗挑战。新型抗纤维化药物和免疫抑制剂的使用有望减缓 RA-ILD 的进展。
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引用次数: 0
Describing calcium pyrophosphate deposition: undoing the tower of Babel! 描述焦磷酸钙沉积:打破巴别塔!
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-01-31 DOI: 10.1097/BOR.0000000000001001
Silvia Sirotti, Robert Terkeltaub, Georgios Filippou

Purpose of review: In 1977, McCarty astutely observed, 'The variety of names suggested for the condition associated with deposits of calcium pyrophosphate dihydrate crystals is exceeded only by the variations of its clinical presentation'. Fast forward to 2024, a standardized nomenclature for calcium pyrophosphate deposition (CPPD) is still lacking. This review aims to delineate the challenges in characterizing CPPD through nomenclature and imaging.

Recent findings: Despite the effort of nomenclature standardization in 2011 by the EULAR, confusion persists in the literature and clinical practice, with pseudo-forms and obscure abbreviations. The Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) has launched a project to redefine CPPD nomenclature and formulate a user-friendly language for effective communication with patients and other stakeholders. Additionally, recent advancements in imaging, have shed light on various aspects of the disorder.

Summary: Almost 60 years from the first description of a clinical manifestation related to calcium pyrophosphate crystals, a common language describing the disorder is still lacking. A redefined CPPD nomenclature, together with lay-friendly terminology, would significantly contribute to the uniformity of CPPD research, enhance public understanding and awareness and improve doctor-patient communication and therefore disease outcomes. Imaging can provide deep insights into CPPD elements, promoting comprehension of this disorder.

审查目的:1977 年,麦卡蒂(McCarty)敏锐地指出:"焦磷酸钙二水结晶沉积症的病名多种多样,只有其临床表现的多样性才能与之媲美"。"时至 2024 年,焦磷酸钙沉积症(CPPD)仍然缺乏标准化的命名。本综述旨在通过命名法和影像学描述 CPPD 所面临的挑战:尽管 EULAR 在 2011 年努力实现术语标准化,但文献和临床实践中仍存在混乱,存在伪式和晦涩的缩写。痛风、高尿酸血症和晶体相关疾病网络(G-CAN)发起了一个项目,旨在重新定义CPPD术语,并制定一种用户友好型语言,以便与患者和其他利益相关者进行有效沟通。此外,影像学的最新进展也揭示了该疾病的各个方面。摘要:从首次描述焦磷酸钙结晶相关临床表现至今已近 60 年,但描述该疾病的通用语言仍然缺乏。重新定义的焦磷酸钙结晶症命名法以及通俗易懂的术语将极大地促进焦磷酸钙结晶症研究的统一性,增强公众的理解和认识,改善医患沟通,从而改善疾病预后。影像学可以深入揭示 CPPD 的要素,促进对这一疾病的理解。
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引用次数: 0
Emerging biologic therapies for systemic lupus erythematosus. 治疗系统性红斑狼疮的新兴生物疗法。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-02-01 DOI: 10.1097/BOR.0000000000001003
Hiroshi Kato, J Michelle Kahlenberg

Purpose of review: The approval of belimumab and anifrolumab has expanded the scope of treatment for systemic lupus erythematosus (SLE) patients. However, many patients remain refractory to currently available therapies and suffer from drug toxicities. This review will discuss approved and target-specific therapeutics in development that bring hope for better SLE treatments.

Recent findings: Since the last review on this subject in the journal, the FDA has approved anifrolumab and belimumab for SLE and lupus nephritis (LN), respectively. A fully humanized anti-CD20, obinutuzumab, met the primary end point in a phase II trial in LN. A Tyk2 inhibitor, deucravacitinib, and an antibody targeting plasmacytoid dendritic cells, litifilimab, met the primary end point in phase II trials in SLE and cutaneous lupus erythematosus (CLE). Ustekinumab and baricitinib met the primary end point in phase II but not in phase III trials.

Summary: While many drug candidates which met the end points in phase II trials have failed phase III trials, the number of target-specific therapies for SLE has continued to expand.

审查目的:贝利木单抗(belimumab)和阿尼单抗(anifrolumab)的批准扩大了系统性红斑狼疮(SLE)患者的治疗范围。然而,许多患者对目前可用的疗法仍不耐受,并遭受药物毒性的折磨。本综述将讨论已获批准和正在开发中的靶向治疗药物,它们为更好地治疗系统性红斑狼疮带来了希望:最近的发现:自本刊上一篇相关综述发表以来,美国食品和药物管理局(FDA)已批准阿尼单抗(anifrolumab)和贝利木单抗(belimumab)分别用于系统性红斑狼疮和狼疮肾炎(LN)。一种全人源化的抗CD20药物obinutuzumab在狼疮肾炎的II期试验中达到了主要终点。一种Tyk2抑制剂deucravacitinib和一种靶向浆细胞树突状细胞的抗体litifilimab在系统性红斑狼疮和皮肤红斑狼疮(CLE)的II期试验中达到了主要终点。总结:虽然许多在II期试验中达到终点的候选药物在III期试验中失败了,但治疗系统性红斑狼疮的靶向特异性疗法的数量仍在继续增加。
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引用次数: 0
Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis? 钠-葡萄糖共转运体 2 抑制剂:它们准备好进入狼疮肾炎治疗的黄金时代了吗?
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-01-31 DOI: 10.1097/BOR.0000000000001002
Benjamin R Wagner, Panduranga S Rao

Purpose of review: Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis.

Recent findings: SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity.

Summary: SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.

审查目的:狼疮肾炎是系统性红斑狼疮的常见并发症,与严重的发病率和死亡率有关。钠-葡萄糖共转运体 2(SGLT2)抑制剂在治疗狼疮性肾炎方面的作用目前尚不确定。在此,我们总结了狼疮肾炎患者使用SGLT2抑制剂的理由:SGLT2 抑制剂最初是作为降血糖药物开发的。此后,在对慢性肾病患者、伴有或不伴有糖尿病的患者以及伴有或不伴有蛋白尿的患者进行的大型临床试验中,SGLT2 抑制剂被证明在减缓慢性肾病的进展和降低心血管疾病的长期风险方面具有额外的深远影响。由于担心感染风险,近期接受过免疫抑制治疗的患者被排除在这些试验之外。在少数针对狼疮肾炎患者的小型试验中,SGLT2 抑制剂的耐受性良好。研究显示,它们可以减少狼疮性肾炎患者的蛋白尿,对血压和体重指数也有一定的益处。总结:SGLT2 抑制剂在减轻狼疮性肾炎对肾脏和心血管的慢性影响方面可能发挥作用。SGLT2抑制剂应在使用适当的免疫抑制剂稳定肾功能后,与血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂一起使用。目前,它们在活动性疾病中没有作用。
{"title":"Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis?","authors":"Benjamin R Wagner, Panduranga S Rao","doi":"10.1097/BOR.0000000000001002","DOIUrl":"10.1097/BOR.0000000000001002","url":null,"abstract":"<p><strong>Purpose of review: </strong>Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis.</p><p><strong>Recent findings: </strong>SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity.</p><p><strong>Summary: </strong>SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.</p>","PeriodicalId":11145,"journal":{"name":"Current opinion in rheumatology","volume":null,"pages":null},"PeriodicalIF":5.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rheumatoid arthritis - the challenge of heterogeneity. 类风湿性关节炎--异质性的挑战。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-26 DOI: 10.1097/BOR.0000000000001005
David A Fox
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引用次数: 0
Safety of biologic agents for the management of rheumatic diseases during pregnancy. 治疗妊娠期风湿病的生物制剂的安全性。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-03-08 DOI: 10.1097/BOR.0000000000001014
Jonathan D D'Gama, Bonnie L Bermas

Purpose of review: To discuss the current understanding regarding the use of biologic therapeutics in pregnancy.

Recent findings: Our understanding of the mechanisms underlying the potential fetal and infant exposure to biologics as well as a growing body of empirical evidence from real world use of biologics in pregnancy have demonstrated that biologics are generally compatible preconception and during pregnancy. Long-term effects of exposure to biologic agents in utero are not known, but will be uncovered in time. Biosimilars, which are becoming more popular, may not always share the same safety profiles as their originators.

Summary: Biologics have revolutionized the management of rheumatologic disease and ushered in a new era of clinical remission among patients. These agents, developed and introduced into clinical use at the beginning of the new millennium, are very potent, yet their efficacy in treating disease often in reproductive aged women, raises questions regarding their safety during pregnancy. These therapeutics can cause immunosuppression and can inhibit immunologic circuits that are not only involved in disease pathophysiology but hypothetically could impact the development of the fetal immune system. Reassuringly, biologics, typically antibodies or antibody-based proteins, are introduced to the fetus via the typical route of transplacental antibody transfer, and thus only begin to be transferred in appreciable amounts in the second trimester (after organogenesis). From theoretic and empirical standpoints, biologic use during pregnancy appears well tolerated for fetal development and to not substantially affect infant immune development.

综述目的讨论目前对妊娠期使用生物制剂治疗的认识:我们对胎儿和婴儿可能暴露于生物制剂的机制的了解,以及越来越多的妊娠期实际使用生物制剂的经验证据表明,生物制剂在孕前和妊娠期通常是兼容的。宫内暴露于生物制剂的长期影响尚不清楚,但随着时间的推移将会揭晓。生物仿制药越来越受欢迎,但其安全性不一定与原研药相同。摘要:生物制剂彻底改变了风湿病的治疗方法,并开创了患者临床缓解的新纪元。这些药物是在新千年之初开发并投入临床使用的,具有很强的疗效,但它们在治疗育龄妇女疾病方面的疗效却引发了有关其在妊娠期安全性的问题。这些疗法会导致免疫抑制,抑制免疫回路,而免疫回路不仅参与疾病的病理生理学,而且可能影响胎儿免疫系统的发育。令人欣慰的是,生物制剂(通常是抗体或基于抗体的蛋白质)是通过典型的经胎盘抗体转移途径进入胎儿体内的,因此只有在妊娠后三个月(器官形成之后)才开始以可观的数量转移。从理论和经验的角度来看,妊娠期使用生物制剂对胎儿的发育似乎具有良好的耐受性,不会对婴儿的免疫发育产生重大影响。
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引用次数: 0
Cardiovascular complications of rheumatoid arthritis. 类风湿性关节炎的心血管并发症。
IF 5.1 2区 医学 Q1 Medicine Pub Date : 2024-05-01 Epub Date: 2024-02-09 DOI: 10.1097/BOR.0000000000001004
Elizabeth Park, Joan Bathon

Purpose of review: Rheumatoid arthritis (RA) patients remain at higher cardiovascular (CV) risk compared to non-RA patients, driven by accelerated atherosclerosis, leading to plaque rupture and acute CV events (CVE), including heart failure (HF). It has been hypothesized that chronic inflammation is the main driving force behind such outcomes. We summarize the current evidence supporting this hypothesis, focusing on arterial disease and myocardial disease.

Recent findings: RA patients demonstrate higher prevalence of subclinical atherosclerosis (high risk plaque and arterial inflammation) compared to non-RA patients, with RA disease activity correlating independently with CVE and death. Nonischemic HF with preserved ejection fraction (HFpEF) is more common in RA compared to non-RA, with subclinical myocardial structural and functional alterations also more prevalent in RA. HFpEF and myocardial remodeling and dysfunction bear a strong and independent association with inflammatory correlates.

Summary: All of this suggests that inflammation contributes to enhanced risk of CVE in RA. A more accurate and specific CV risk stratification tool for RA, incorporating biomarkers or imaging, is needed. Likewise, more prospective studies outlining the trajectory from preclinical to clinical HF, incorporating biomarkers and imaging, are also needed.

综述目的:与非类风湿性关节炎(RA)患者相比,类风湿性关节炎(RA)患者的心血管(CV)风险仍然较高,原因是动脉粥样硬化加速,导致斑块破裂和急性 CV 事件(CVE),包括心力衰竭(HF)。据推测,慢性炎症是造成这种结果的主要原因。我们总结了目前支持这一假设的证据,重点关注动脉疾病和心肌疾病:与非 RA 患者相比,RA 患者亚临床动脉粥样硬化(高危斑块和动脉炎症)的发病率更高,RA 疾病活动与 CVE 和死亡独立相关。与非RA患者相比,射血分数保留的非缺血性心房颤动(HFpEF)在RA患者中更为常见,亚临床心肌结构和功能改变在RA患者中也更为普遍。HFpEF和心肌重塑及功能障碍与炎症相关性有很强的独立关联。我们需要一种结合生物标志物或成像技术的更准确、更具体的 RA CV 风险分层工具。同样,还需要进行更多的前瞻性研究,结合生物标志物和成像技术,勾勒出从临床前高血压到临床高血压的发展轨迹。
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引用次数: 0
Chimeric antigen receptors: "CARs" in the fast lane for rheumatology. 嵌合抗原受体:风湿病学快车道上的 "CAR"。
IF 5.2 2区 医学 Q1 RHEUMATOLOGY Pub Date : 2024-05-01 Epub Date: 2024-03-26 DOI: 10.1097/BOR.0000000000001012
Nathan M Johnson, Fotios Koumpouras

Purpose of review: Recent advances in hematology-oncology have pioneered cell-mediated elimination of pathologic B-cell populations employing chimeric antigen receptor (CAR) T cells. In this review, we discuss recent adoption of CAR-T treatment for severe refractory autoimmune disease. We highlight unique aspects of the autoimmune model and review current clinical data regarding treatment of rheumatologic disease.

Recent findings: To date, several CAR-Ts are FDA approved for Multiple Myeloma and B-cell malignancies and have demonstrated extraordinary clinical responses in refractory disease. Realizing the central role of B-cells in certain autoimmune diseases, CAR-T is now being explored for achieving drug-free remission induction, and potentially cure, of several rheumatologic diseases. The largest experience to date in the field of autoimmunity, building off the University Hospital Erlangen groups' earlier success treating a single patient with CD19-CAR in severe refractory SLE, Mackensen et al. enrolled five patients in a compassionate use program. Following autologous CD19-CAR T infusion, they demonstrated drug-free clinical and laboratory remission for at least 12 months in all five patients, with reconstitution of B cells expressing a naïve phenotype.

Summary: CAR-T treatment has shown striking drug-free responses in severe lupus and other autoimmune diseases, creating a need for further exploration and development.

综述的目的:血液肿瘤学的最新进展开创了利用嵌合抗原受体(CAR)T 细胞通过细胞介导消除病理性 B 细胞群的方法。在这篇综述中,我们讨论了最近采用 CAR-T 治疗严重难治性自身免疫性疾病的情况。我们强调了自身免疫模型的独特之处,并回顾了目前治疗风湿病的临床数据:迄今为止,美国食品及药物管理局(FDA)已批准几种CAR-T用于治疗多发性骨髓瘤和B细胞恶性肿瘤,并已在难治性疾病中显示出非凡的临床反应。由于认识到 B 细胞在某些自身免疫性疾病中的核心作用,CAR-T 目前正被用于实现无药缓解诱导,并有可能治愈多种风湿性疾病。埃尔兰根大学医院的研究小组早先成功用 CD19-CAR 治疗了一名重症难治性系统性红斑狼疮患者,在此基础上,Mackensen 等人又在一项同情使用计划中招募了五名患者,这是迄今为止自身免疫领域最大规模的治疗。在自体 CD19-CAR T 细胞输注后,他们证明所有五名患者的临床和实验室治疗均在至少 12 个月内无药物缓解,并重建了表达天真表型的 B 细胞。摘要:CAR-T 治疗已在重症狼疮和其他自身免疫性疾病中显示出惊人的无药物反应,因此需要进一步探索和开发。
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引用次数: 0
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Current opinion in rheumatology
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