Pub Date : 2025-01-15DOI: 10.1038/s41584-024-01210-9
Marit Stockfelt, Y. K. Onno Teng, Edward M. Vital
B cell depletion with rituximab, a chimeric monoclonal antibody that selectively targets B cells by binding CD20, has been used off label in severe and resistant systemic lupus erythematosus (SLE) for over two decades. Several biological mechanisms limit the efficacy of rituximab, including immunological reactions towards the chimeric molecule, increased numbers of residual B cells, including plasmablasts and plasma cells, and a post-treatment surge in B cell-activating factor (BAFF) levels. Consequently, rituximab induces remission in only a proportion of patients, and safety issues limit its use. However, the use of rituximab has established the value of B cell depletion strategies in SLE and has guided the development of several improved B cell depletion therapies for SLE. These include enhanced monoclonal antibodies, modalities that redirect the specificity of patient T cells using chimeric antigen receptor T cells or bispecific T cell engagers, and combination treatment that simultaneously inhibits the BAFF pathway. In this Review, we consider evidence gathered from over two decades of using rituximab in SLE and examine how B cell depletion therapies could be further optimized to achieve immunological and clinical efficacy. In addition, we discuss the prospects of B cell depletion strategies for personalized treatment in SLE based on genetic research and studies in pre-symptomatic individuals.
{"title":"Opportunities and limitations of B cell depletion approaches in SLE","authors":"Marit Stockfelt, Y. K. Onno Teng, Edward M. Vital","doi":"10.1038/s41584-024-01210-9","DOIUrl":"https://doi.org/10.1038/s41584-024-01210-9","url":null,"abstract":"<p>B cell depletion with rituximab, a chimeric monoclonal antibody that selectively targets B cells by binding CD20, has been used off label in severe and resistant systemic lupus erythematosus (SLE) for over two decades. Several biological mechanisms limit the efficacy of rituximab, including immunological reactions towards the chimeric molecule, increased numbers of residual B cells, including plasmablasts and plasma cells, and a post-treatment surge in B cell-activating factor (BAFF) levels. Consequently, rituximab induces remission in only a proportion of patients, and safety issues limit its use. However, the use of rituximab has established the value of B cell depletion strategies in SLE and has guided the development of several improved B cell depletion therapies for SLE. These include enhanced monoclonal antibodies, modalities that redirect the specificity of patient T cells using chimeric antigen receptor T cells or bispecific T cell engagers, and combination treatment that simultaneously inhibits the BAFF pathway. In this Review, we consider evidence gathered from over two decades of using rituximab in SLE and examine how B cell depletion therapies could be further optimized to achieve immunological and clinical efficacy. In addition, we discuss the prospects of B cell depletion strategies for personalized treatment in SLE based on genetic research and studies in pre-symptomatic individuals.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"27 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981504","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 : 2025-01-10DOI: 10.1038/s41584-024-01215-4
Holly Webster
A study implicates the Hes1–Piezo1 signalling pathway in osteocytes in the pathogenesis of glucocorticoid-induced osteoporosis and demonstrates the beneficial effects of Yoda1, a Piezo1 agonist.
{"title":"Piezo1 as a therapeutic target for glucocorticoid-induced osteoporosis","authors":"Holly Webster","doi":"10.1038/s41584-024-01215-4","DOIUrl":"https://doi.org/10.1038/s41584-024-01215-4","url":null,"abstract":"A study implicates the Hes1–Piezo1 signalling pathway in osteocytes in the pathogenesis of glucocorticoid-induced osteoporosis and demonstrates the beneficial effects of Yoda1, a Piezo1 agonist.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"20 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939529","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 : 2025-01-10DOI: 10.1038/s41584-024-01204-7
Hannah C. Ainsworth, DeAnna Baker Frost, S. Sam Lim, Paula S. Ramos
Health disparities in rheumatic disease are well established and urgently need addressing. Obstacles to precision medicine equity span both the clinical and the research domains, with a focus placed on structural barriers limiting equitable health care access and inclusivity in research. Less articulated factors include the use of inaccurate population descriptors and the existence of research silos in rheumatology research, which creates a knowledge gap that precludes addressing the health disparities and fulfilling the goals of precision medicine to understand the ‘full patient’. The biopsychosocial model is a research framework that intertwines layers of biological and environmental effects to understand disease. However, very limited rheumatology research bridges across molecular and epidemiological studies of environmental exposures, such as physical and social determinants of health. In this Review, we discuss clinical obstacles to health care equity, including access to health care and the use of inaccurate language when labelling population groups. We explore the goals and data needed for research under the biopsychosocial model. We describe results from a rheumatic disease literature search that highlights the paucity of studies investigating the molecular influences of systemic exposures. We conclude with a list of considerations and recommendations to help achieve equitable precision medicine.
{"title":"Breaking research silos to achieve equitable precision medicine in rheumatology","authors":"Hannah C. Ainsworth, DeAnna Baker Frost, S. Sam Lim, Paula S. Ramos","doi":"10.1038/s41584-024-01204-7","DOIUrl":"https://doi.org/10.1038/s41584-024-01204-7","url":null,"abstract":"<p>Health disparities in rheumatic disease are well established and urgently need addressing. Obstacles to precision medicine equity span both the clinical and the research domains, with a focus placed on structural barriers limiting equitable health care access and inclusivity in research. Less articulated factors include the use of inaccurate population descriptors and the existence of research silos in rheumatology research, which creates a knowledge gap that precludes addressing the health disparities and fulfilling the goals of precision medicine to understand the ‘full patient’. The biopsychosocial model is a research framework that intertwines layers of biological and environmental effects to understand disease. However, very limited rheumatology research bridges across molecular and epidemiological studies of environmental exposures, such as physical and social determinants of health. In this Review, we discuss clinical obstacles to health care equity, including access to health care and the use of inaccurate language when labelling population groups. We explore the goals and data needed for research under the biopsychosocial model. We describe results from a rheumatic disease literature search that highlights the paucity of studies investigating the molecular influences of systemic exposures. We conclude with a list of considerations and recommendations to help achieve equitable precision medicine.</p>","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"50 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142939507","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 : 2025-01-02DOI: 10.1038/s41584-024-01214-5
Ewa M. Roos
In 2024, studies using more advanced methods to calculate the minimal important change have described how different methods and timings of estimating minimal important changes can affect the estimates.
{"title":"Advances in the calculation of minimal important change estimates for patient-reported outcome measures","authors":"Ewa M. Roos","doi":"10.1038/s41584-024-01214-5","DOIUrl":"https://doi.org/10.1038/s41584-024-01214-5","url":null,"abstract":"In 2024, studies using more advanced methods to calculate the minimal important change have described how different methods and timings of estimating minimal important changes can affect the estimates.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"34 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911486","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 : 2024-12-23DOI: 10.1038/s41584-024-01209-2
Shiwen Yuan, David J. Hunter
Results of the STEP 9 trial show that semaglutide leads to improvements in knee osteoarthritis-related symptoms. The findings support weight-management pharmacotherapies as a feasible option for management of knee osteoarthritis, but cost-effectiveness, risk of toxicity and likelihood of rebound must be considered.
{"title":"Precision weight management in people with knee osteoarthritis and overweight or obesity","authors":"Shiwen Yuan, David J. Hunter","doi":"10.1038/s41584-024-01209-2","DOIUrl":"https://doi.org/10.1038/s41584-024-01209-2","url":null,"abstract":"Results of the STEP 9 trial show that semaglutide leads to improvements in knee osteoarthritis-related symptoms. The findings support weight-management pharmacotherapies as a feasible option for management of knee osteoarthritis, but cost-effectiveness, risk of toxicity and likelihood of rebound must be considered.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"24 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874052","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 : 2024-12-20DOI: 10.1038/s41584-024-01213-6
Maria Papatriantafyllou
Synovial dendritic cell profiles and localization patterns provide insights about the roles of dendritic cell subsets in the initiation, remission and relapse of rheumatoid arthritis.
滑膜树突状细胞谱和定位模式提供了树突状细胞亚群在类风湿关节炎的起始、缓解和复发中的作用。
{"title":"Synovial dendritic cell subsets in RA","authors":"Maria Papatriantafyllou","doi":"10.1038/s41584-024-01213-6","DOIUrl":"https://doi.org/10.1038/s41584-024-01213-6","url":null,"abstract":"Synovial dendritic cell profiles and localization patterns provide insights about the roles of dendritic cell subsets in the initiation, remission and relapse of rheumatoid arthritis.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"40 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866964","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 : 2024-12-20DOI: 10.1038/s41584-024-01211-8
Sarah Onuora
In a new study, inhibition of CDK7 disrupted the RNA polymerase II transcription cycle, leading to anti-inflammatory effects and metabolic reprogramming in macrophages and attenuation of arthritis in mouse models.
{"title":"Blocking CDK7 attenuates inflammatory arthritis","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01211-8","DOIUrl":"https://doi.org/10.1038/s41584-024-01211-8","url":null,"abstract":"In a new study, inhibition of CDK7 disrupted the RNA polymerase II transcription cycle, leading to anti-inflammatory effects and metabolic reprogramming in macrophages and attenuation of arthritis in mouse models.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"14 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866965","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 : 2024-12-20DOI: 10.1038/s41584-024-01205-6
Robyn T. Domsic
The updated 2023 EULAR recommendations for treatment of systemic sclerosis bring notable changes to recommendations for skin, peripheral vascular disease, interstitial lung disease and pulmonary arterial hypertension therapies, based on newer evidence. These updates provide the first glimmer of personalized patient management.
{"title":"European expert recommendations for managing systemic sclerosis and its complications","authors":"Robyn T. Domsic","doi":"10.1038/s41584-024-01205-6","DOIUrl":"https://doi.org/10.1038/s41584-024-01205-6","url":null,"abstract":"The updated 2023 EULAR recommendations for treatment of systemic sclerosis bring notable changes to recommendations for skin, peripheral vascular disease, interstitial lung disease and pulmonary arterial hypertension therapies, based on newer evidence. These updates provide the first glimmer of personalized patient management.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"30 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866966","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 : 2024-12-20DOI: 10.1038/s41584-024-01208-3
Coziana Ciurtin, Elizabeth C. Jury
Here, we highlight three publications in 2024 that have advanced the field of molecular and immunological profiling, for the diagnosis, prognosis and treatment of patients with systemic autoimmune rheumatic diseases.
{"title":"Molecular profiling for advancing precision rheumatology","authors":"Coziana Ciurtin, Elizabeth C. Jury","doi":"10.1038/s41584-024-01208-3","DOIUrl":"https://doi.org/10.1038/s41584-024-01208-3","url":null,"abstract":"Here, we highlight three publications in 2024 that have advanced the field of molecular and immunological profiling, for the diagnosis, prognosis and treatment of patients with systemic autoimmune rheumatic diseases.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"32 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866967","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 : 2024-12-20DOI: 10.1038/s41584-024-01212-7
Sarah Onuora
In a phase III clinical trial of abatacept for idiopathic inflammatory myopathy, the primary endpoint was not met but the results suggest abatacept could have benefits in some subtypes of the disease.
{"title":"Abatacept for myositis","authors":"Sarah Onuora","doi":"10.1038/s41584-024-01212-7","DOIUrl":"https://doi.org/10.1038/s41584-024-01212-7","url":null,"abstract":"In a phase III clinical trial of abatacept for idiopathic inflammatory myopathy, the primary endpoint was not met but the results suggest abatacept could have benefits in some subtypes of the disease.","PeriodicalId":18810,"journal":{"name":"Nature Reviews Rheumatology","volume":"25 1","pages":""},"PeriodicalIF":33.7,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867113","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}
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