Best Practice & Research in Clinical Rheumatology最新文献

{"title":"Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies","authors":"Jisna R. Paul ,&nbsp;Prateek C. Gandiga ,&nbsp;Rohit Aggarwal","doi":"10.1016/j.berh.2026.102140","DOIUrl":"10.1016/j.berh.2026.102140","url":null,"abstract":"<div><div>Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell– targeted therapies. While monoclonal antibody–based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success.</div><div>Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to “immune reset” with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM.</div><div>This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102140"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147976997","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}

{"title":"CAR T cell therapy: Autoimmune neurological uses and neurotoxicities","authors":"Alec R. Friedman ,&nbsp;Sara Gil-Perotin ,&nbsp;Sarah Flanagan Wesley","doi":"10.1016/j.berh.2026.102145","DOIUrl":"10.1016/j.berh.2026.102145","url":null,"abstract":"<div><div>Chimeric antigen receptor T cell therapy (CAR-T) represents a growing field of cell therapy for the treatment of a range of oncological and autoimmune conditions. From the neurological perspective, it remains limited by immunotoxicities, in particular immune effector cell-associated neurotoxicity syndrome (ICANS) and non-ICANS neurotoxicities, such as movement disorders (parkinsonism) and neurocognitive toxicity, neuropathies, myelopathies, and tumor inflammation-associated neurotoxicity. Despite these potential adverse effects, CAR-T remains promising for the treatment of refractory autoimmune neurological conditions, including myasthenia gravis, multiple sclerosis, chronic inflammatory demyelinating polyneuropathies, stiff person syndrome, and others. CAR-T use for autoimmune neurological disorders marks an exciting paradigm shift from immune suppression to immune reprogramming. Moreover, given success in several T-cell mediated autoimmune conditions, these successful results extend the therapeutic scope of B-cell-targeted CAR-T approaches.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102145"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617163","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}

{"title":"Cellular therapies in systemic Sclerosis: immunopathogenesis-informed precision targeting with CAR-T and CAR-NK approaches","authors":"Gerard Convey ,&nbsp;Masataka Kuwana ,&nbsp;Mandana Nikpour","doi":"10.1016/j.berh.2026.102139","DOIUrl":"10.1016/j.berh.2026.102139","url":null,"abstract":"<div><div>Systemic sclerosis (SSc) is a rare, heterogeneous systemic autoimmune rheumatic disease characterized by immune dysregulation, vasculopathy, and excessive fibrosis. SSc is associated with high morbidity and mortality despite current immunosuppressive and anti-fibrotic therapies. Emerging cellular therapies, particularly chimeric antigen receptor (CAR) T-cell and natural killer (NK) cell approaches offer potential for deep immune reset and long-term remission. This review examines the immunobiological rationale for these therapies in SSc and evaluates their early clinical evidence, including comparisons to other autoimmune diseases.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102139"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617092","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}

{"title":"Bridging clinical phenotypes with molecular mechanisms in autoimmune irAEs: An Etiopathogenic framework","authors":"Whitney Elg-Salsman","doi":"10.1016/j.berh.2026.102152","DOIUrl":"10.1016/j.berh.2026.102152","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICI) have transformed the field of oncology and can induce a durable cancer treatment response in select cancer patients. ICI binding to these checkpoints allows the immune system to be activated in order to target tumor death, but this activation also brings multiple off-target side effects called immune related adverse events (irAE's) including rheumatic irAE's. Review aims will explore novel insights into rheumatic irAE's etiology and etiopathology including ICI-inflammatory arthritis, ICI-Polymyalgia Rheumatica, ICI-activated osteoarthritis, sicca-like syndrome, and ICI induced myositis. This chapter will review rheumatic irAE's and define their proposed mechanisms, which include generalized immune activation owing to checkpoint neutralization, direct off-target effects of checkpoint inhibitors and epitope spreading. Research using cellular profiling methods such as single cell transcriptomics and T cell profiling have helped explore the novel mechanism of these heterogenous rheumatic irAE's. Future goals of research include gaining a better understanding of pathogenesis of rheumatic irAE's to help target precision rheumatic irAE treatment.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102152"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876353","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}

{"title":"CAR T-cell therapy “Living drugs” in systemic lupus erythematosus","authors":"Leila Khalili ,&nbsp;Alberto Nordmann-Gomes ,&nbsp;Marta Mosca ,&nbsp;Anca Askanase","doi":"10.1016/j.berh.2026.102141","DOIUrl":"10.1016/j.berh.2026.102141","url":null,"abstract":"<div><h3>Introduction</h3><div>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).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102141"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","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}

{"title":"Introduction to the issue: Cellular therapies in rheumatology","authors":"Anca Askanase ,&nbsp;Marta Mosca","doi":"10.1016/j.berh.2026.102160","DOIUrl":"10.1016/j.berh.2026.102160","url":null,"abstract":"","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102160"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147935257","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}

{"title":"T-cell engagers in rheumatology","authors":"Alberto Nordmann-Gomes ,&nbsp;Leila Khalili ,&nbsp;Stephen Wax ,&nbsp;Anca Askanase","doi":"10.1016/j.berh.2026.102146","DOIUrl":"10.1016/j.berh.2026.102146","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>This narrative review summarizes the biological rationale, structural diversity, dosing strategies, and emerging clinical efficacy and safety regarding the use of TCEs in rheumatology.</div></div><div><h3>Results</h3><div>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<strong>.</strong> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102146"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","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}

{"title":"Erratum to “Editorial Board” [Best Pract Res Clin Rheumatol (2025) 102094]","authors":"","doi":"10.1016/j.berh.2026.102120","DOIUrl":"10.1016/j.berh.2026.102120","url":null,"abstract":"","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102120"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148247574","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}

{"title":"Malignancy and rheumatic diseases","authors":"Savannah Bowman ,&nbsp;Maria E. Suarez-Almazor","doi":"10.1016/j.berh.2026.102142","DOIUrl":"10.1016/j.berh.2026.102142","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102142"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","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}

{"title":"The management of rheumatic immune related adverse events","authors":"Pankti Reid ,&nbsp;Namrata Singh ,&nbsp;Tawnie Braaten ,&nbsp;Laura C. Cappelli","doi":"10.1016/j.berh.2026.102147","DOIUrl":"10.1016/j.berh.2026.102147","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICI) used for the treatment of cancer can cause immune related adverse events (irAEs) when immune activation affects non-tumor tissues. Rheumatologists care for patients with a variety of rheumatic irAEs; these included inflammatory arthritis (ICI-IA), polymyalgia rheumatica (ICI-PMR), and myositis (ICI-myositis) among others. Rheumatic irAEs are commonly impactful on patients’ quality of life and function and sometimes can cause significant morbidity and mortality. This review will highlight the diagnosis and assessment of rheumatic irAEs. Then treatment for individual irAEs will be discussed in depth with considerations to supportive care, corticosteroid dosing and tapering, steroid sparing immunosuppression and monitoring. Finally, the safety of immunosuppression as it relates to tumor outcomes and considerations by oncologists when selecting ICI therapy will be reviewed.</div></div>","PeriodicalId":50983,"journal":{"name":"Best Practice & Research in Clinical Rheumatology","volume":"40 1","pages":"Article 102147"},"PeriodicalIF":4.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147845853","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}