Pub Date : 2025-12-08DOI: 10.1038/s41584-025-01333-7
Ivonne Melano, M. Elaine Husni, Nicolas S. Piuzzi, Suan-Sin Foo, Weiqiang Chen
Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus–autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations. In this Review, the authors summarize the potential role of emerging viruses in autoimmune rheumatic diseases (AIRDs). They describe the association between viruses and AIRD flare ups, the putative mechanisms linking AIRD to viral infections and hormone modulation of viral pathogenesis and autoimmune diseases.
{"title":"Emerging and underrecognized viral triggers of autoimmune inflammatory rheumatic disease flares","authors":"Ivonne Melano, M. Elaine Husni, Nicolas S. Piuzzi, Suan-Sin Foo, Weiqiang Chen","doi":"10.1038/s41584-025-01333-7","DOIUrl":"10.1038/s41584-025-01333-7","url":null,"abstract":"Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus–autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations. In this Review, the authors summarize the potential role of emerging viruses in autoimmune rheumatic diseases (AIRDs). They describe the association between viruses and AIRD flare ups, the putative mechanisms linking AIRD to viral infections and hormone modulation of viral pathogenesis and autoimmune diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"118-131"},"PeriodicalIF":32.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-08DOI: 10.1038/s41584-025-01336-4
Andras Perl
Endosomal traffic governs various core processes that maintain immune homeostasis and self-tolerance, including receptor signalling, antigen processing, cytokine secretion and cellular metabolism. Traffic-regulated receptors - both intracellular and on the cell surface - modulate immune sensing of infection, nutrient availability and endogenous stress signals arising from cellular or tissue injury. In rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren syndrome and osteoarthritis, mounting evidence implicates disruptions in endosomal pathways as important drivers of disease onset and progression. Dysregulated endosomal trafficking contributes to type I interferon activation via signalling through Toll-like receptors, aberrant autoantigen presentation, and altered expression of metabolite transporters in immune cells and target organs. Endosome trafficking mediates autophagosome formation, the production of exosomes and the turnover of organelles, such as mitochondria that generate oxidative stress, thereby controlling chronic inflammation and connective tissue remodelling. Therefore, understanding the molecular architecture of endosomal recycling pathways and their integration with immune cell function can provide important insight into rheumatic diseases. Restoring trafficking fidelity - through modulation of RAB GTPases, endosomal Toll-like receptor signalling, metabolic reprogramming, autophagic flux and extracellular vesicle biology - represents a promising therapeutic strategy.
{"title":"Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.","authors":"Andras Perl","doi":"10.1038/s41584-025-01336-4","DOIUrl":"https://doi.org/10.1038/s41584-025-01336-4","url":null,"abstract":"Endosomal traffic governs various core processes that maintain immune homeostasis and self-tolerance, including receptor signalling, antigen processing, cytokine secretion and cellular metabolism. Traffic-regulated receptors - both intracellular and on the cell surface - modulate immune sensing of infection, nutrient availability and endogenous stress signals arising from cellular or tissue injury. In rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, systemic sclerosis, Sjögren syndrome and osteoarthritis, mounting evidence implicates disruptions in endosomal pathways as important drivers of disease onset and progression. Dysregulated endosomal trafficking contributes to type I interferon activation via signalling through Toll-like receptors, aberrant autoantigen presentation, and altered expression of metabolite transporters in immune cells and target organs. Endosome trafficking mediates autophagosome formation, the production of exosomes and the turnover of organelles, such as mitochondria that generate oxidative stress, thereby controlling chronic inflammation and connective tissue remodelling. Therefore, understanding the molecular architecture of endosomal recycling pathways and their integration with immune cell function can provide important insight into rheumatic diseases. Restoring trafficking fidelity - through modulation of RAB GTPases, endosomal Toll-like receptor signalling, metabolic reprogramming, autophagic flux and extracellular vesicle biology - represents a promising therapeutic strategy.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-05DOI: 10.1038/s41584-025-01340-8
Jessica McHugh
A new study uncovers how UBA1 mutations in VEXAS syndrome simultaneously promote myeloid inflammatory cell death and skew haematopoietic stem cells towards a myeloid lineage.
{"title":"Unravelling the cellular mechanisms of VEXAS syndrome","authors":"Jessica McHugh","doi":"10.1038/s41584-025-01340-8","DOIUrl":"10.1038/s41584-025-01340-8","url":null,"abstract":"A new study uncovers how UBA1 mutations in VEXAS syndrome simultaneously promote myeloid inflammatory cell death and skew haematopoietic stem cells towards a myeloid lineage.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 1","pages":"5-5"},"PeriodicalIF":32.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1038/s41584-025-01337-3
Rachel Knevel
Advances in artificial intelligence (AI) are transforming patient stratification in rheumatology. In 2025, three landmark studies demonstrated how multimodal AI approaches spanning clinical, molecular and longitudinal data can uncover distinct disease subtypes and predict therapeutic response, advancing the field towards precision rheumatology.
{"title":"Advances in AI-based patient stratification for rheumatic diseases","authors":"Rachel Knevel","doi":"10.1038/s41584-025-01337-3","DOIUrl":"10.1038/s41584-025-01337-3","url":null,"abstract":"Advances in artificial intelligence (AI) are transforming patient stratification in rheumatology. In 2025, three landmark studies demonstrated how multimodal AI approaches spanning clinical, molecular and longitudinal data can uncover distinct disease subtypes and predict therapeutic response, advancing the field towards precision rheumatology.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"75-77"},"PeriodicalIF":32.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-03DOI: 10.1038/s41584-025-01332-8
Kelsey H. Collins, Ida K. Haugen, Tuhina Neogi, Farshid Guilak
Osteoarthritis (OA) is a painful disorder of the synovial joints characterized by dysfunctional cellular metabolism and extracellular matrix degradation that activates maladaptive repair responses, including pro-inflammatory pathways of innate immunity. OA has historically been viewed as an unavoidable consequence of ageing owing to wear-and-tear of the joint. Most strategies to mitigate OA have primarily focused on the articular cartilage and, more recently, other specific joint tissues, which limits understanding of OA as a systemic disease beyond the joint. Preclinical and clinical data support a paradigm shift in understanding OA as a disease of the whole person, focusing on changes throughout the body that both promote and are caused by OA. This shift provides novel insights into why preclinical research findings have not been successfully translated into clinical therapies. Moreover, a viable strategy for OA drug development could be to treat pain separately from OA structural damage. Challenging classically held views that lack evidence or have been disproven is required for progress. We explore some key emerging questions that should be carefully considered in future OA studies. Adapting and integrating new technologies, techniques, and tools into the rapidly evolving understanding of OA could lead to the development of drugs that might not only treat OA but also provide mechanistic insight into other conditions that result from the dysregulation of systemic factors or from the communication breakdown in inter-organ crosstalk. Such developments would reposition OA researchers from adapting approaches from other fields of science and medicine to leaders in the fight against chronic disease. Emerging evidence suggests a paradigm shift in viewing osteoarthritis (OA) as a systemic, bidirectional disease. This Review examines the current data supporting this concept, outlines key challenges in research approaches, and proposes strategies to improve preclinical studies and clinical trial design.
{"title":"Osteoarthritis as a systemic disease","authors":"Kelsey H. Collins, Ida K. Haugen, Tuhina Neogi, Farshid Guilak","doi":"10.1038/s41584-025-01332-8","DOIUrl":"10.1038/s41584-025-01332-8","url":null,"abstract":"Osteoarthritis (OA) is a painful disorder of the synovial joints characterized by dysfunctional cellular metabolism and extracellular matrix degradation that activates maladaptive repair responses, including pro-inflammatory pathways of innate immunity. OA has historically been viewed as an unavoidable consequence of ageing owing to wear-and-tear of the joint. Most strategies to mitigate OA have primarily focused on the articular cartilage and, more recently, other specific joint tissues, which limits understanding of OA as a systemic disease beyond the joint. Preclinical and clinical data support a paradigm shift in understanding OA as a disease of the whole person, focusing on changes throughout the body that both promote and are caused by OA. This shift provides novel insights into why preclinical research findings have not been successfully translated into clinical therapies. Moreover, a viable strategy for OA drug development could be to treat pain separately from OA structural damage. Challenging classically held views that lack evidence or have been disproven is required for progress. We explore some key emerging questions that should be carefully considered in future OA studies. Adapting and integrating new technologies, techniques, and tools into the rapidly evolving understanding of OA could lead to the development of drugs that might not only treat OA but also provide mechanistic insight into other conditions that result from the dysregulation of systemic factors or from the communication breakdown in inter-organ crosstalk. Such developments would reposition OA researchers from adapting approaches from other fields of science and medicine to leaders in the fight against chronic disease. Emerging evidence suggests a paradigm shift in viewing osteoarthritis (OA) as a systemic, bidirectional disease. This Review examines the current data supporting this concept, outlines key challenges in research approaches, and proposes strategies to improve preclinical studies and clinical trial design.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"105-117"},"PeriodicalIF":32.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-02DOI: 10.1038/s41584-025-01296-9
Juhi R. Kuchroo, Naomi Goldman, Arlene H. Sharpe
Immune-checkpoint molecules have essential roles in regulating immune responses, which maintain the delicate balance between physiological immune reactions and autoimmunity. The clinical success of immune checkpoint blockade for cancer therapy, and the occurrence of immune-related adverse events during cancer immunotherapy, highlight the profound effect of modulating these receptors on both tumour-specific and ‘self’-specific responses. As a result, interest in exploring how these molecules can be targeted to treat autoimmune and rheumatological diseases is expanding. Targeting of the immune-checkpoint molecules PD-1, B and T lymphocyte attenuator (BTLA) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) to induce immune tolerance has shown therapeutic promise in pre-clinical models and, in some instances, clinical trials. A comprehensive understanding of how these receptors function in various immune cell populations, particularly T cells, and across different diseases is crucial for the successful translation of these findings to clinical applications. Immune-checkpoint agonists are a promising therapeutic approach for autoimmune disease. This Review discusses the immune-checkpoint receptors PD-1, BTLA and TIGIT as well as the preclinical and clinical evidence for therapeutically targeting these receptors for the treatment of rheumatic diseases.
{"title":"PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease","authors":"Juhi R. Kuchroo, Naomi Goldman, Arlene H. Sharpe","doi":"10.1038/s41584-025-01296-9","DOIUrl":"10.1038/s41584-025-01296-9","url":null,"abstract":"Immune-checkpoint molecules have essential roles in regulating immune responses, which maintain the delicate balance between physiological immune reactions and autoimmunity. The clinical success of immune checkpoint blockade for cancer therapy, and the occurrence of immune-related adverse events during cancer immunotherapy, highlight the profound effect of modulating these receptors on both tumour-specific and ‘self’-specific responses. As a result, interest in exploring how these molecules can be targeted to treat autoimmune and rheumatological diseases is expanding. Targeting of the immune-checkpoint molecules PD-1, B and T lymphocyte attenuator (BTLA) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) to induce immune tolerance has shown therapeutic promise in pre-clinical models and, in some instances, clinical trials. A comprehensive understanding of how these receptors function in various immune cell populations, particularly T cells, and across different diseases is crucial for the successful translation of these findings to clinical applications. Immune-checkpoint agonists are a promising therapeutic approach for autoimmune disease. This Review discusses the immune-checkpoint receptors PD-1, BTLA and TIGIT as well as the preclinical and clinical evidence for therapeutically targeting these receptors for the treatment of rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"89-104"},"PeriodicalIF":32.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1038/s41584-025-01339-1
Christine T. N. Pham, Farshid Guilak
Many of the current therapies for arthritis lack a targeted approach, limiting clinical benefits. Nanoparticle-based delivery systems have enabled more precise and efficient delivery of therapeutic agents, particularly nucleic acids. Studies in 2025 emphasize the promise of these strategies for the treatment of various forms of arthritis.
{"title":"Advances in RNA-based nanotherapies for arthritis","authors":"Christine T. N. Pham, Farshid Guilak","doi":"10.1038/s41584-025-01339-1","DOIUrl":"10.1038/s41584-025-01339-1","url":null,"abstract":"Many of the current therapies for arthritis lack a targeted approach, limiting clinical benefits. Nanoparticle-based delivery systems have enabled more precise and efficient delivery of therapeutic agents, particularly nucleic acids. Studies in 2025 emphasize the promise of these strategies for the treatment of various forms of arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"80-81"},"PeriodicalIF":32.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-28DOI: 10.1038/s41584-025-01338-2
Maria Papatriantafyllou
T helper 17 cells that lose IL-17 expression drive inflammation in a mouse model of chronic rheumatoid arthritis.
在慢性类风湿关节炎小鼠模型中，失去IL-17表达的T辅助17细胞驱动炎症。
{"title":"ExTH17 cells maintain chronic inflammation in RA","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-025-01338-2","DOIUrl":"10.1038/s41584-025-01338-2","url":null,"abstract":"T helper 17 cells that lose IL-17 expression drive inflammation in a mouse model of chronic rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"74-74"},"PeriodicalIF":32.7,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1038/s41584-025-01329-3
Fabian Proft, Andre L. Ribeiro, Shikha Singla, Vinod Chandran, Wilson Liao, Christine Lindsay, Enrique R. Soriano, Tina Bhutani, Atul Deodhar, Kurt de Vlam, Lihi Eder, Mitsumasa Kishimoto, Ying Ying Leung, Ennio Lubrano, Dennis McGonagle, Denis Poddubnyy, Laura Savage, Filip Van den Bosch, Philip Mease
Despite advances in the treatment of psoriatic arthritis (PsA), a substantial proportion of patients continue to report persistent symptoms and impaired quality of life. However, terminology remains inconsistent for patients who fail to achieve disease control despite treatment, which limits research comparability and contributes to therapeutic inertia. To address this gap, a Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) task force developed consensus definitions for two distinct states: complex-to-manage PsA (C2M-PsA) and treatment-refractory PsA (TR-PsA). C2M-PsA is defined as a state of persistent symptoms despite treatment with at least one biologic or targeted synthetic DMARD (b/tsDMARD), extending beyond biological non-response to include factors such as comorbidities, overlapping conditions, psychosocial burden and treatment-related challenges (for example, non-adherence). TR-PsA, a more specific subset of C2M-PsA, is characterized by failure of at least three therapies with distinct mechanisms of action (including at least two biologic/targeted synthetic DMARDs), persistent symptoms considered problematic by both patient and clinician, and objective evidence of ongoing inflammation — after ruling out alternative explanations for treatment refractoriness. These consensus-derived GRAPPA definitions provide a shared framework to standardize terminology, support individualized care, and improve patient stratification in research and practice. Prospective validation across diverse settings and phenotypes is needed to confirm their reliability, responsiveness and clinical utility. In this Consensus Statement, a Group for Research and Assessment of Psoriasis and Psoriatic Arthritis task force presents consensus definitions for two distinct states, complex-to-manage PsA and treatment-refractory PsA, with the aim of standardizing terminology, improving patient stratification and guiding clinical decision-making and future research.
{"title":"Consensus definitions of complex-to-manage and treatment-refractory psoriatic arthritis: a GRAPPA initiative","authors":"Fabian Proft, Andre L. Ribeiro, Shikha Singla, Vinod Chandran, Wilson Liao, Christine Lindsay, Enrique R. Soriano, Tina Bhutani, Atul Deodhar, Kurt de Vlam, Lihi Eder, Mitsumasa Kishimoto, Ying Ying Leung, Ennio Lubrano, Dennis McGonagle, Denis Poddubnyy, Laura Savage, Filip Van den Bosch, Philip Mease","doi":"10.1038/s41584-025-01329-3","DOIUrl":"10.1038/s41584-025-01329-3","url":null,"abstract":"Despite advances in the treatment of psoriatic arthritis (PsA), a substantial proportion of patients continue to report persistent symptoms and impaired quality of life. However, terminology remains inconsistent for patients who fail to achieve disease control despite treatment, which limits research comparability and contributes to therapeutic inertia. To address this gap, a Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) task force developed consensus definitions for two distinct states: complex-to-manage PsA (C2M-PsA) and treatment-refractory PsA (TR-PsA). C2M-PsA is defined as a state of persistent symptoms despite treatment with at least one biologic or targeted synthetic DMARD (b/tsDMARD), extending beyond biological non-response to include factors such as comorbidities, overlapping conditions, psychosocial burden and treatment-related challenges (for example, non-adherence). TR-PsA, a more specific subset of C2M-PsA, is characterized by failure of at least three therapies with distinct mechanisms of action (including at least two biologic/targeted synthetic DMARDs), persistent symptoms considered problematic by both patient and clinician, and objective evidence of ongoing inflammation — after ruling out alternative explanations for treatment refractoriness. These consensus-derived GRAPPA definitions provide a shared framework to standardize terminology, support individualized care, and improve patient stratification in research and practice. Prospective validation across diverse settings and phenotypes is needed to confirm their reliability, responsiveness and clinical utility. In this Consensus Statement, a Group for Research and Assessment of Psoriasis and Psoriatic Arthritis task force presents consensus definitions for two distinct states, complex-to-manage PsA and treatment-refractory PsA, with the aim of standardizing terminology, improving patient stratification and guiding clinical decision-making and future research.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"22 2","pages":"132-144"},"PeriodicalIF":32.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41584-025-01329-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145608735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1038/s41584-025-01328-4
Joshua Heerey, Joanne Kemp, Pim van Klij, Vasco Mascarenhas, Mark Scholes, Fleur Boel, Paul Dijkstra, Kay Crossley, Sita Bierma-Zeinstra, Rintje Agricola
{"title":"Cam morphology and the development of femoroacetabular impingement syndrome and hip osteoarthritis","authors":"Joshua Heerey, Joanne Kemp, Pim van Klij, Vasco Mascarenhas, Mark Scholes, Fleur Boel, Paul Dijkstra, Kay Crossley, Sita Bierma-Zeinstra, Rintje Agricola","doi":"10.1038/s41584-025-01328-4","DOIUrl":"https://doi.org/10.1038/s41584-025-01328-4","url":null,"abstract":"","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"13 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：