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CAR-T cell therapy for ANCA-associated vasculitis: Rationale, current evidence, and future directions CAR-T细胞治疗anca相关性血管炎：理论基础、现有证据和未来方向
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2026-03-01 Epub Date: 2026-04-08 DOI: 10.1016/j.berh.2026.102144
Rachel Tate , Brian Jaros , Anisha Dua
{"title":"CAR-T cell therapy for ANCA-associated vasculitis: Rationale, current evidence, and future directions","authors":"Rachel Tate ,&nbsp;Brian Jaros ,&nbsp;Anisha Dua","doi":"10.1016/j.berh.2026.102144","DOIUrl":"10.1016/j.berh.2026.102144","url":null,"abstract":"<div><div>Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a relapsing, autoantibody-driven disease in which current therapies often fail to achieve durable remission or are limited by cumulative toxicity. Although CD20-directed B-cell depletion has transformed AAV management, persistent autoreactive B-cells and long-lived, tissue-resident plasma cells contribute to refractory disease and relapse. Chimeric antigen receptor (CAR) T-cell therapy offers a mechanistically distinct approach through deep and sustained depletion of pathogenic B-cell lineages and potential “immune reprogramming.” Emerging clinical experience in autoimmune diseases, coupled with preclinical models and early case reports in AAV, has demonstrated rapid disease control, marked reductions in ANCA levels, and prolonged immunologic quiescence following CD19 CAR-T therapy. While safety signals in autoimmune populations appear favorable, critical questions remain regarding the durability of response, long-term immunologic consequences, optimal CAR constructs, and patient selection. This review summarizes the immunopathogenic rationale, existing evidence, safety considerations, and future directions for CAR-based therapies in AAV.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102144"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640422","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
Contemporary approaches to the management of rheumatoid arthritis: precision and progress 类风湿关节炎的当代治疗方法：精确与进步。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.berh.2025.102106
Tania Gudu , Mert Oztas , Elena Nikiphorou
{"title":"Contemporary approaches to the management of rheumatoid arthritis: precision and progress","authors":"Tania Gudu ,&nbsp;Mert Oztas ,&nbsp;Elena Nikiphorou","doi":"10.1016/j.berh.2025.102106","DOIUrl":"10.1016/j.berh.2025.102106","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting synovial joints and extra-articular organs. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) like methotrexate remain the cornerstone of therapy, nearly half of patients demonstrate inadequate response to monotherapy. This review provides a comprehensive overview of the evolving therapeutic landscape in RA, covering standard therapies, novel treatments, and precision medicine approaches. The treatment landscape has dramatically expanded with biologic DMARDs targeting TNF-α, IL-6, B and T cells, and more recently, targeted synthetic DMARDs such as the Janus kinase inhibitors (JAKi). Emerging therapies are discussed, including innovative cell-based approaches, that will likely continue to revolutionize the treatment o. Furthermore, treatment failure, in the context of difficult-to-treat disease and factors associated with this, are addressed. We explore biomarker-driven treatment selection utilizing autoantibodies, imaging, and synovial tissue analysis and address key challenges around drug safety concerns, managing comorbidities and difficult-to-treat RA. Finally, this article concludes with reflections on future directions and the role of machine learning, multi-omics technologies, while maintaining the focus on patient-centered approaches to care.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102106"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214343","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
Novel Therapy 新颖的治疗。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-09-26 DOI: 10.1016/j.berh.2025.102103
Mitsumasa Kishimoto MD, PhD , Peter Nash MD
{"title":"Novel Therapy","authors":"Mitsumasa Kishimoto MD, PhD ,&nbsp;Peter Nash MD","doi":"10.1016/j.berh.2025.102103","DOIUrl":"10.1016/j.berh.2025.102103","url":null,"abstract":"","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102103"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180235","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
Novel therapies for axial spondyloarthritis and future directions 轴性脊柱炎的新疗法及未来发展方向。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI: 10.1016/j.berh.2025.102105
Marta Dzhus , Walter P. Maksymowych
{"title":"Novel therapies for axial spondyloarthritis and future directions","authors":"Marta Dzhus ,&nbsp;Walter P. Maksymowych","doi":"10.1016/j.berh.2025.102105","DOIUrl":"10.1016/j.berh.2025.102105","url":null,"abstract":"<div><div>This update explores emerging therapeutic strategies aimed at novel targets implicated in the pathogenesis of axSpA. Recent clinical trials of bimekizumab, a monoclonal antibody targeting both IL-17A and IL-17F, and janus-kinase inhibitors have demonstrated significant and sustained improvements in clinical and imaging outcomes, with a favorable safety profile and reduced rates of uveitis. Investigational agents targeting GM-CSF and MK2 have not demonstrated efficacy, but the targeting of autoreactive T cell clonotypes shared among individuals with axSpA using depleting antibodies to the variable gene segment 9 of the T cell receptor beta chain appears promising. Preclinical investigation has focused on cytokines, such as macrophage inflammatory protein, and kinases, such as mammalian target of rapamycin and phosphoinositide 3-kinase, and transcriptional factors, such as retinoic acid receptor-related orphan receptor-yt that regulate expression of IL-17A and -F cytokines. Several advances in therapeutic technologies also hold promise for more effective therapeutics based on current targets.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102105"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145276190","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
Novel therapies in osteoporosis – Clinical update – 2025 骨质疏松症的新疗法-临床更新- 2025。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 10.1016/j.berh.2025.102100
Charles Inderjeeth, Diren Che Inderjeeth
{"title":"Novel therapies in osteoporosis – Clinical update – 2025","authors":"Charles Inderjeeth,&nbsp;Diren Che Inderjeeth","doi":"10.1016/j.berh.2025.102100","DOIUrl":"10.1016/j.berh.2025.102100","url":null,"abstract":"<div><div>Rheumatological patients are at high risk of osteoporosis and fracture due to disease, treatments, comorbidity and physical and functional considerations. Treating osteoporosis optimally is paramount. Osteoporosis management is evolving rapidly beyond traditional therapies. This 2025 review examines available traditional therapies and novel pharmacological approaches developed. Key questions addressed include the mechanisms, efficacy, and safety of agents like the sclerostin inhibitor romosozumab, Parathyroid hormone targeted agents, cytokine inhibitors and the status of therapies targeting cathepsin K. We evaluate the growing importance of combined and sequential treatment strategies, particularly initiating potent anabolic or dual-action therapies followed by antiresorptives for high-risk patients. Furthermore, the review explores emerging therapeutic targets such as modulators of the Wnt pathway, inflammation, and bone cell metabolism, alongside advancements in drug delivery, gene therapy, and non-pharmacological interventions. Clinical implications for patient selection, monitoring, and navigating the expanding treatment landscape are discussed, highlighting future directions towards personalized osteoporosis care.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102100"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151689","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
Novel therapies in treatments of SLE SLE治疗的新疗法。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-10-07 DOI: 10.1016/j.berh.2025.102101
Yoshiya Tanaka
{"title":"Novel therapies in treatments of SLE","authors":"Yoshiya Tanaka","doi":"10.1016/j.berh.2025.102101","DOIUrl":"10.1016/j.berh.2025.102101","url":null,"abstract":"<div><div>Systemic lupus erythematosus (SLE) is an autoimmune disease that damages multiple organs. Glucocorticoids (GCs) have been a mainstay of the treatment of SLE, but it is strongly recommended to minimize GCs usage due to the toxicity of long-term use. Currently, development of molecular-targeted therapies based on pathological mechanisms is underway. Activation of B cells through T-B cell interaction play a central role in the pathogenesis, and treatments targeting B cells and co-stimulatory molecules are expected. In addition, many disease susceptibility genes are mediated in signaling by the innate immune mechanisms, such as dendritic cells involvement and cytokines production that stimulates acquired immunity, as well as kinases of intracellular signaling molecules that are described as targets. Furthermore, adoptive transfer of T cells engineered to target CD19 antigen by gene transfer of chimeric antigen receptor and by T cell engagers that recruit T cells and induce B cell cytotoxicity gather attention.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102101"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253228","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
What's new in osteoarthritis? 骨关节炎有什么新进展？
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.berh.2025.102102
Graeme Jones
{"title":"What's new in osteoarthritis?","authors":"Graeme Jones","doi":"10.1016/j.berh.2025.102102","DOIUrl":"10.1016/j.berh.2025.102102","url":null,"abstract":"<div><div>Osteoarthritis is major and growing public health problem. Major advances have occurred in terms of understanding the pathogenesis of the disease primarily due to advances in imaging. Both systemic and local factors are involved. Some of these are modifiable making them attractive targets for therapy and the development of precision medicine in osteoarthritis. A growing number of these trials selecting subgroups of osteoarthritis with specific imaging features have been completed with mixed results. In many cases, the interventional studies have not replicated the results of the basic science and human observational studies and the majority of trials have been negative with a few notable exceptions. There is an urgent need for greater choice of therapies in this condition.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102102"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214362","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
IgG4-Related disease: From diagnosis to remission igg4相关疾病：从诊断到缓解。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-11-14 DOI: 10.1016/j.berh.2025.102108
Arjun Mahajan , Alex Tinianow , Guy Katz
{"title":"IgG4-Related disease: From diagnosis to remission","authors":"Arjun Mahajan ,&nbsp;Alex Tinianow ,&nbsp;Guy Katz","doi":"10.1016/j.berh.2025.102108","DOIUrl":"10.1016/j.berh.2025.102108","url":null,"abstract":"<div><div>Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder that can affect many organ systems. This chapter provides a comprehensive overview of current knowledge regarding IgG4-RD, addressing key questions about disease mechanisms, diagnostic approaches, and therapeutic strategies. We examine the diverse clinical manifestations ranging from glandular enlargement to life-threatening vascular involvement, emphasizing the importance of recognizing both inflammatory and fibrotic disease phenotypes. Diagnostic approaches integrate clinical symptoms, imaging findings, histopathological features, and serological markers while excluding mimicking conditions. Treatment strategies have evolved significantly with the introduction of B cell depletion therapy, particularly inebilizumab. Current treatment paradigms must prioritize glucocorticoid-sparing approaches, though maintenance therapy considerations remain complex. Critical knowledge gaps persist regarding optimal biomarkers for disease activity, standardized remission criteria, and the precise etiopathogenesis of IgG4-RD. Despite therapeutic advances, challenges remain in balancing effective disease control with minimizing the harms of long-term immunosuppression, emphasizing the need for continued research into targeted therapies.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102108"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530788","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
Emerging therapies in idiopathic inflammatory myopathies: Advances in treatment and future directions 特发性炎症性肌病的新疗法：治疗进展和未来方向。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-11-09 DOI: 10.1016/j.berh.2025.102107
Laure Gallay , Eaman Alhassan , Niladri Bhowmick , Rohit Aggarwal
{"title":"Emerging therapies in idiopathic inflammatory myopathies: Advances in treatment and future directions","authors":"Laure Gallay ,&nbsp;Eaman Alhassan ,&nbsp;Niladri Bhowmick ,&nbsp;Rohit Aggarwal","doi":"10.1016/j.berh.2025.102107","DOIUrl":"10.1016/j.berh.2025.102107","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies are a group of rare autoimmune diseases characterized by chronic muscle inflammation and variable systemic involvement. Although conventional therapies, including corticosteroids and immunosuppressants, form the cornerstone of treatment, most patients do not achieve remission, underscoring the need for more effective options. Advances in understanding disease pathogenesis have led to the development of novel targeted therapies. Strategies aimed at disrupting key immune pathways, such as interferon signaling, T cell activation, and B cell maturation, have shown promising results. Additionally, innovative approaches such as engineered cellular therapies are currently explored. These treatments offer the potential to achieve deeper and more durable disease control, reduce corticosteroid dependence, and improve quality of life for the patients. In this chapter, we present the recent findings on novel therapies for the treatment of IIM (all subtypes except IBM) by discussing the rationale behind their use, their potential role in improving patient outcomes in the different IIM subtypes, as well as the limitations of their wide implementation. Future strategies and promising therapies under investigation are also highlighted.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102107"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490760","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
Novel therapies – IMID Co-morbidities 新疗法- IMID合并症。
IF 4.8 2区 医学
Best Practice & Research in Clinical Rheumatology Pub Date : 2025-12-01 Epub Date: 2025-08-12 DOI: 10.1016/j.berh.2025.102089
Tsz On Lam, Ho So, Lai-Shan Tam
{"title":"Novel therapies – IMID Co-morbidities","authors":"Tsz On Lam,&nbsp;Ho So,&nbsp;Lai-Shan Tam","doi":"10.1016/j.berh.2025.102089","DOIUrl":"10.1016/j.berh.2025.102089","url":null,"abstract":"<div><div>Cardiovascular diseases (CVD) and metabolic syndrome are common in patients with immune-mediated inflammatory diseases (IMID). These conditions exhibit significant interactions, between diseases and in relation to treatments, highlighting the need for rheumatologists to take an active role in their management. It is now known that inflammation mediated by adipokines is important in the pathogenesis of obesity and cardiovascular-kidney-metabolic (CKM) syndrome. Novel therapeutics developed for metabolic comorbidities have demonstrated pleiotropic benefit across a range of diseases. Some of them even possess anti-inflammatory and immuno-modulatory effects, serving as adjuncts to the management of IMID. On the other hand, anti-inflammatory drugs have been rigorously tested for their efficacy in CVD and colchicine has become the first anti-inflammatory drug approved for this purpose. This paper will focus on the novel therapeutics and new purposes of conventional drugs in the management of CVD and metabolic syndrome, with additional discussion of their relevance in IMID.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"39 4","pages":"Article 102089"},"PeriodicalIF":4.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849532","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
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