Best Practice & Research in Clinical Rheumatology最新文献_第2页

CAR T-cell therapy "Living drugs" in systemic lupus erythematosus. CAR - t细胞治疗系统性红斑狼疮的“活药”。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-08 DOI: 10.1016/j.berh.2026.102141

Leila Khalili, Alberto Nordmann-Gomes, Marta Mosca, Anca Askanase

{"title":"CAR T-cell therapy \"Living drugs\" in systemic lupus erythematosus.","authors":"Leila Khalili, Alberto Nordmann-Gomes, Marta Mosca, Anca Askanase","doi":"10.1016/j.berh.2026.102141","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102141","url":null,"abstract":"Introduction: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative therapeutic option for patients with severe, refractory autoimmune conditions. Since 2022, several authors have published their experience using CAR T-cell therapy for patients with systemic lupus erythematosus (SLE).Methods: This narrative review summarizes the biological rationale, diverse modalities, targets and platforms, the emerging clinical efficacy and safety data, as well as the barriers and innovations regarding the use of CAR T-cell therapy in SLE.Results: Among the 16 studies reviewed, 13 evaluated products targeting CD19 and the remaining three bispecific products targeting CD19 and B-cell maturation antigen (BCMA). Twelve studies assessed autologous therapies and four allogeneic products. Therapies evaluating CAR natural killer cells (CAR-NK), gamma delta T-cells (γδ T-cells), other transduction methods, and even in vivo CARs are currently being evaluated. Early data has demonstrated significant clinical efficacy, including rapid disease activity reductions, drug-free remission in over 80%, achievement of low-level disease activity in almost 90%, and remission in 70% of the patients where these outcomes were assessed. Cytokine release syndrome occurred in 56% of the patients evaluated, almost exclusively being grade 1 or 2 events, and neurotoxicity was rare.Conclusions: CAR T-cell therapy has demonstrated encouraging clinical efficacy and reassuring safety outcomes so far. However, longer prospective studies are needed to assess durability of response, long term safety, factors associated with poor response, and the appropriate selection and timing of patients for therapy.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102141"},"PeriodicalIF":4.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147646921","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

T-cell engagers in rheumatology. 风湿病中的t细胞接合物。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-08 DOI: 10.1016/j.berh.2026.102146

Alberto Nordmann-Gomes, Leila Khalili, Stephen Wax, Anca Askanase

{"title":"T-cell engagers in rheumatology.","authors":"Alberto Nordmann-Gomes, Leila Khalili, Stephen Wax, Anca Askanase","doi":"10.1016/j.berh.2026.102146","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102146","url":null,"abstract":"Introduction: T-cell engagers (TCEs) have transformed the treatment of hematologic malignancies. Given the central role of B-cells in the pathogenesis of many autoimmune diseases, there has been growing interest in expanding the use of TCEs to rheumatologic indications as a simpler alternative to CAR-T.Methods: This narrative review summarizes the biological rationale, structural diversity, dosing strategies, and emerging clinical efficacy and safety regarding the use of TCEs in rheumatology.Results: Among 12 studies reviewed, 80 patients received a TCE: 33 for SLE, 22 for RA, 14 for SSc, 6 for IIM, 2 for PSS, and 3 for other indications. Thirty-two patients received blinatumomab, 16 teclistamab, 15 mosunetuzumab, and 17 another TCE. Early signs of clinical improvement were observed, including rapid disease activity reduction, improvement in organ-specific manifestations, and normalization of serologic biomarkers. Nonetheless, many patients experienced persistent or recurrent disease activity after treatment discontinuation. There was substantial heterogeneity in dosing strategies across studies, with lower cumulative exposure and shorter treatment duration compared with regimens used in oncology, suggesting potential undertreatment may contribute to lower response rates and disease recurrence in some patients. CRS was observed in 46% of patients, of which 33% were grade 1, 12% were grade 2, and 1% was grade 3. No neurotoxicity or deaths have been reported.Conclusion: TCEs demonstrated encouraging early efficacy and acceptable safety across several refractory autoimmune diseases, supporting their potential role as a novel therapeutic strategy. Longer prospective studies are needed to define adequate dosing schedules, long-term safety, and durability of response.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102146"},"PeriodicalIF":4.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640405","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

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 : 2026-04-08 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, Brian Jaros, Anisha Dua","doi":"10.1016/j.berh.2026.102144","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102144","url":null,"abstract":"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.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102144"},"PeriodicalIF":4.8,"publicationDate":"2026-04-08","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

State of the art and novel treatments in psoriatic arthritis. 银屑病关节炎的最新治疗方法。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-08 DOI: 10.1016/j.berh.2026.102135

Simon Hackett, Hussein Al-Mossawi, Laura C Coates

{"title":"State of the art and novel treatments in psoriatic arthritis.","authors":"Simon Hackett, Hussein Al-Mossawi, Laura C Coates","doi":"10.1016/j.berh.2026.102135","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102135","url":null,"abstract":"Psoriatic arthritis (PsA) is a heterogeneous, immune-mediated inflammatory disease characterised by multidomain clinical involvement, including peripheral arthritis, enthesitis, axial disease, dactylitis, and skin and nail manifestations, alongside a substantial burden of comorbidity. Over the recent decades, therapeutic options for PsA have expanded, with the introduction of multiple biologic and targeted compounds targeting tumour necrosis factor, the IL-23/IL-17 axis, and Janus kinase signalling. These advances have improved outcomes for many patients; however, incomplete responses, domain-specific refractory disease, treatment intolerance, and loss of efficacy remain common. In addition, current treatment strategies are largely reactive, reflecting limited ability to predict treatment response or align immune mechanism with clinical phenotype. This review summarises the current PsA treatment landscape and its limitations, and examines emerging therapeutic directions that aim to address disease heterogeneity and unmet need. These include combinatorial and sequential treatment strategies, next-generation biologics and oral agents, immunometabolic modulation, selective targeting of pathogenic immune cell populations and upstream inflammatory, immune tolerance-based approaches. It is with hope that these developments highlight a shift from incremental therapeutic expansion towards a integrated, targeted and ultimately, more informed treatment approach.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102135"},"PeriodicalIF":4.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647177","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

Renal involvement in systemic sclerosis. 系统性硬化症累及肾脏。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-06 DOI: 10.1016/j.berh.2026.102138

Ibraheem M Almani, Janet E Pope

{"title":"Renal involvement in systemic sclerosis.","authors":"Ibraheem M Almani, Janet E Pope","doi":"10.1016/j.berh.2026.102138","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102138","url":null,"abstract":"Systemic sclerosis is a complex connective tissue disease characterized by immune dysregulation, widespread vasculopathy, and progressive fibrosis affecting the skin and internal organs. Among its visceral complications, renal involvement, manifesting as scleroderma renal crisis, remains organ and life-threatening if not detected. Although its mortality has markedly declined with the life-saving introduction of angiotensin-converting enzyme inhibitors, renal complications remain a major determinant of morbidity, mortality, and long-term health outcomes. Beyond scleroderma renal crisis, a spectrum of renal abnormalities, and secondary renal injury from hypertension or therapeutic agents, contribute to the overall disease burden. This chapter review synthesizes evidence to provide an in-depth analysis of renal involvement in systemic sclerosis. The epidemiology, pathophysiology, clinical presentation, diagnostic approaches, management strategies, and emerging research directions are reviewed, along with developments in precision medicine, single-cell sequencing, molecular profiling, and complement-directed therapies are also discussed, highlighting gaps and future directions to optimize positive outcomes.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102138"},"PeriodicalIF":4.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635179","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

Malignancy and rheumatic diseases. 恶性肿瘤和风湿病。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-03 DOI: 10.1016/j.berh.2026.102142

Savannah Bowman, Maria E Suarez-Almazor

{"title":"Malignancy and rheumatic diseases.","authors":"Savannah Bowman, Maria E Suarez-Almazor","doi":"10.1016/j.berh.2026.102142","DOIUrl":"https://doi.org/10.1016/j.berh.2026.102142","url":null,"abstract":"Several systemic autoimmune rheumatic diseases carry an increased risk of malignancy compared to the general population, including dermatomyositis, Sjogren's disease (SjD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). This is likely a result of chronic inflammation, impaired tumor surveillance related to treatments, and shared risk factors, such as smoking. As treatments for systemic autoimmune rheumatic diseases continue to expand and cancer survival continues to improve, clinicians and patients are increasingly faced with complex decisions regarding the treatment of rheumatic autoimmune diseases in patients with current or prior malignancy. This review describes the risk of malignancy across the most common autoimmune diseases, highlights cancer screening recommendations in this patient population, and examines the evidence on the risk of de novo malignancy, or cancer progression and recurrence with the use of several biologic and targeted synthetic disease-modifying anti-rheumatic drugs. We also highlight important management considerations when selecting therapies to treat autoimmune diseases in patients with current or recent cancer.","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":" ","pages":"102142"},"PeriodicalIF":4.8,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619040","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

CAR T cell therapy: Autoimmune neurological uses and neurotoxicities. CAR - T细胞疗法：自身免疫神经功能和神经毒性

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-02 DOI: 10.1016/j.berh.2026.102145

Alec R Friedman, Sara Gil-Perotin, Sarah Flanagan Wesley

引用次数: 0

Cellular therapies in systemic Sclerosis: immunopathogenesis-informed precision targeting with CAR-T and CAR-NK approaches. 系统性硬化症的细胞治疗：CAR-T和CAR-NK方法的免疫发病机制信息精确靶向。

IF 4.8 2区医学

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-04-02 DOI: 10.1016/j.berh.2026.102139

Gerard Convey, Masataka Kuwana, Mandana Nikpour

引用次数: 0

Psoriatic arthritis-evolution of our understanding of the phenotype. 银屑病关节炎-我们对表型的理解的演变。