Pub Date : 2024-10-21DOI: 10.1016/S2665-9913(24)00280-7
Chokan Baimukhamedov , Galymzhan Togizbayev
{"title":"Gout in central Asia: a few things make a big difference","authors":"Chokan Baimukhamedov , Galymzhan Togizbayev","doi":"10.1016/S2665-9913(24)00280-7","DOIUrl":"10.1016/S2665-9913(24)00280-7","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142510636","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 : 2024-10-18DOI: 10.1016/S2665-9913(24)00225-X
Yujie Shen, Jinchao Jia, Jialin Teng, Chengde Yang, Qiongyi Hu
Still's disease, a systemic autoinflammatory disorder with a classic multigenetic background, is characterised by polyarthritis, high-spiking fever, salmon-like evanescent skin rash, and hyperferritinaemia. Although the exact cause of Still's disease remains unclear, it is believed to be influenced by genetic factors, infections, and immune dysregulation. Current studies indicate that neutrophils and macrophages play crucial roles in the pathogenesis of Still's disease, along with involvement of natural killer cells, T cells, and B cells. Advances in biologic agents have expanded treatment strategies beyond conventional approaches, with cytokine-targeted agents showing promise in the management of Still's disease. Some cytokine-targeting biologic agents can be developed based on clinical manifestations, complications, immune cells, and molecular networks. Emphasis of immunophenotyping for precise clinical subtyping and targeted molecular therapies based on these findings is crucial for optimising treatment outcomes. In this Review, we discuss the latest advancements in the understanding of Still's disease pathogenesis and corresponding therapeutic approaches.
斯蒂尔病是一种具有典型多基因遗传背景的系统性自身炎症性疾病，其特征是多关节炎、高热、鲑鱼状皮疹和高铁蛋白血症。尽管 Still's 病的确切病因仍不清楚，但据信它受到遗传因素、感染和免疫失调的影响。目前的研究表明，中性粒细胞和巨噬细胞在 Still's 病的发病机制中起着关键作用，自然杀伤细胞、T 细胞和 B 细胞也参与其中。生物制剂的进步使治疗策略超越了传统方法，细胞因子靶向制剂在治疗斯蒂尔病方面大有可为。一些细胞因子靶向生物制剂可根据临床表现、并发症、免疫细胞和分子网络进行开发。强调通过免疫分型进行精确的临床亚型分析，并根据这些发现进行有针对性的分子治疗，对于优化治疗效果至关重要。在本综述中，我们将讨论在了解斯蒂尔病发病机制和相应治疗方法方面取得的最新进展。
{"title":"Advancing personalised precision treatment for Still's disease based on molecular characteristics and disease progression.","authors":"Yujie Shen, Jinchao Jia, Jialin Teng, Chengde Yang, Qiongyi Hu","doi":"10.1016/S2665-9913(24)00225-X","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00225-X","url":null,"abstract":"<p><p>Still's disease, a systemic autoinflammatory disorder with a classic multigenetic background, is characterised by polyarthritis, high-spiking fever, salmon-like evanescent skin rash, and hyperferritinaemia. Although the exact cause of Still's disease remains unclear, it is believed to be influenced by genetic factors, infections, and immune dysregulation. Current studies indicate that neutrophils and macrophages play crucial roles in the pathogenesis of Still's disease, along with involvement of natural killer cells, T cells, and B cells. Advances in biologic agents have expanded treatment strategies beyond conventional approaches, with cytokine-targeted agents showing promise in the management of Still's disease. Some cytokine-targeting biologic agents can be developed based on clinical manifestations, complications, immune cells, and molecular networks. Emphasis of immunophenotyping for precise clinical subtyping and targeted molecular therapies based on these findings is crucial for optimising treatment outcomes. In this Review, we discuss the latest advancements in the understanding of Still's disease pathogenesis and corresponding therapeutic approaches.</p>","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478078","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 : 2024-10-15DOI: 10.1016/S2665-9913(24)00221-2
Mark D Russell, Mark Gibson, Benjamin Zuckerman, Kanta Kumar, Shirish Dubey, Maryam A Adas, Edward Alveyn, Samir Patel, Zijing Yang, Katie Bechman, Elizabeth Price, Sarah Gallagher, Andrew P Cope, Sam Norton, James B Galloway
<p><strong>Background: </strong>Quantifying health-care inequality is essential to addressing the imbalance in outcomes attributable to age, sex, race or ethnicity, and multimorbidity. In this study, we analysed differences in the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis within the universal health-care system of England and Wales, UK.</p><p><strong>Methods: </strong>An observational cohort study was conducted using the National Early Inflammatory Arthritis Audit (NEIAA) dataset. We included all patients with rheumatoid arthritis who were enrolled in NEIAA between May 8, 2018, and April 30, 2022, and who had 12-month follow-up data available. Modified Poisson regression was used to explore factors associated with the initiation of biological and targeted synthetic DMARDs within 12 months of initial rheumatology assessment. The factors evaluated included age, sex, ethnicity, socioeconomic status (index of multiple deprivation), smoking status, and relevant comorbidities (lung disease, cardiovascular disease, cancer, and depression). NEIAA is supported by people with lived experience of rheumatoid arthritis, who contributed to study design and the interpretation of findings.</p><p><strong>Findings: </strong>6098 patients in NEIAA had new diagnoses of rheumatoid arthritis and available follow-up data. The mean age was 59·2 years (SD 14·9); 3912 (64·2%) patients were women and 2186 (35·8%) were men. 6047 (99·2%) patients had available ethnicity data, of whom 5215 (86·2%) were White, 152 (2·5%) were Black, 478 (7·9%) were Asian, and 202 (3·3%) were of mixed or other ethnicities. 508 (8·3%) of 6098 patients initiated biological and targeted synthetic DMARDs within 12 months. Patients younger than 40 years were more likely to be initiated on biological and targeted synthetic DMARDs than individuals older than 65 years (multivariable-adjusted risk ratio 2·41 [95% CI 1·83-3·19]; p<0·0001). Asian individuals were less likely to be initiated on biological and targeted synthetic DMARDs than White individuals (0·52 [0·36-0·76]; p=0·0007), which persisted after adjustment for socioeconomic status, comorbidities, baseline disease severity, and the initial response to conventional synthetic DMARDs. These differences were evident for Asian women but not Asian men. Black individuals were more likely to be initiated on biological and targeted synthetic DMARDs than White individuals (1·54 [1·10-2·16]; p=0·012), which became non-significant after adjusting for baseline disease severity and autoantibody status.</p><p><strong>Interpretation: </strong>The initiation of biological and targeted synthetic DMARDs for patients with newly diagnosed rheumatoid arthritis varies markedly by ethnicity and age in the universal health-care system of England and Wales. This study demonstrates the importance of providing tailored information and ensuring equitable access to high-quality care fo
{"title":"Factors associated with biological and targeted synthetic disease-modifying antirheumatic drug initiation for rheumatoid arthritis in underserved patient groups in England and Wales, UK: a national cohort study.","authors":"Mark D Russell, Mark Gibson, Benjamin Zuckerman, Kanta Kumar, Shirish Dubey, Maryam A Adas, Edward Alveyn, Samir Patel, Zijing Yang, Katie Bechman, Elizabeth Price, Sarah Gallagher, Andrew P Cope, Sam Norton, James B Galloway","doi":"10.1016/S2665-9913(24)00221-2","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00221-2","url":null,"abstract":"<p><strong>Background: </strong>Quantifying health-care inequality is essential to addressing the imbalance in outcomes attributable to age, sex, race or ethnicity, and multimorbidity. In this study, we analysed differences in the initiation of biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis within the universal health-care system of England and Wales, UK.</p><p><strong>Methods: </strong>An observational cohort study was conducted using the National Early Inflammatory Arthritis Audit (NEIAA) dataset. We included all patients with rheumatoid arthritis who were enrolled in NEIAA between May 8, 2018, and April 30, 2022, and who had 12-month follow-up data available. Modified Poisson regression was used to explore factors associated with the initiation of biological and targeted synthetic DMARDs within 12 months of initial rheumatology assessment. The factors evaluated included age, sex, ethnicity, socioeconomic status (index of multiple deprivation), smoking status, and relevant comorbidities (lung disease, cardiovascular disease, cancer, and depression). NEIAA is supported by people with lived experience of rheumatoid arthritis, who contributed to study design and the interpretation of findings.</p><p><strong>Findings: </strong>6098 patients in NEIAA had new diagnoses of rheumatoid arthritis and available follow-up data. The mean age was 59·2 years (SD 14·9); 3912 (64·2%) patients were women and 2186 (35·8%) were men. 6047 (99·2%) patients had available ethnicity data, of whom 5215 (86·2%) were White, 152 (2·5%) were Black, 478 (7·9%) were Asian, and 202 (3·3%) were of mixed or other ethnicities. 508 (8·3%) of 6098 patients initiated biological and targeted synthetic DMARDs within 12 months. Patients younger than 40 years were more likely to be initiated on biological and targeted synthetic DMARDs than individuals older than 65 years (multivariable-adjusted risk ratio 2·41 [95% CI 1·83-3·19]; p<0·0001). Asian individuals were less likely to be initiated on biological and targeted synthetic DMARDs than White individuals (0·52 [0·36-0·76]; p=0·0007), which persisted after adjustment for socioeconomic status, comorbidities, baseline disease severity, and the initial response to conventional synthetic DMARDs. These differences were evident for Asian women but not Asian men. Black individuals were more likely to be initiated on biological and targeted synthetic DMARDs than White individuals (1·54 [1·10-2·16]; p=0·012), which became non-significant after adjusting for baseline disease severity and autoantibody status.</p><p><strong>Interpretation: </strong>The initiation of biological and targeted synthetic DMARDs for patients with newly diagnosed rheumatoid arthritis varies markedly by ethnicity and age in the universal health-care system of England and Wales. This study demonstrates the importance of providing tailored information and ensuring equitable access to high-quality care fo","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478081","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 : 2024-10-11DOI: 10.1016/S2665-9913(24)00223-6
Amanda Malone, Mark M Kowalski, James Helliwell, Sidsel Lynggaard Boll, Helene Rovsing, Kathrine Moriat, Alejandro Castillo Mondragón, Yanqi Li, Claire Prener Miller, Asger Reinstrup Bihlet, Christine Dobek, Vik Peck, Mike Wilmink, Lee S Simon, Philip G Conaghan
<p><strong>Background: </strong>Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis.</p><p><strong>Methods: </strong>SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</p><p><strong>Findings: </strong>Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Ef
{"title":"Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial.","authors":"Amanda Malone, Mark M Kowalski, James Helliwell, Sidsel Lynggaard Boll, Helene Rovsing, Kathrine Moriat, Alejandro Castillo Mondragón, Yanqi Li, Claire Prener Miller, Asger Reinstrup Bihlet, Christine Dobek, Vik Peck, Mike Wilmink, Lee S Simon, Philip G Conaghan","doi":"10.1016/S2665-9913(24)00223-6","DOIUrl":"https://doi.org/10.1016/S2665-9913(24)00223-6","url":null,"abstract":"<p><strong>Background: </strong>Corticosteroids are among the few effective treatments for knee osteoarthritis, but short duration of action limits their utility. EP-104IAR, a long-acting formulation of fluticasone propionate for intra-articular injection, optimises the action of fluticasone propionate through novel diffusion-based extended-release technology. The SPRINGBOARD trial assessed the efficacy, safety, and pharmacokinetics of EP-104IAR in people with knee osteoarthritis.</p><p><strong>Methods: </strong>SPRINGBOARD was a randomised, vehicle-controlled, double-blind, phase 2 trial done at 12 research sites in Denmark, Poland, and Czech Republic. We recruited adults aged 40 years or older with primary knee osteoarthritis (Kellgren-Lawrence grade 2-3) who reported Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain scores of at least 4 and no more than 9 out of 10. Participants were randomly assigned (1:1) to receive one intra-articular dose of 25 mg EP-104IAR or vehicle control. Randomisation was done via interactive web-based access to a central predefined computer-generated list with block size of six (allocated by clinical site). Participants and assessors were masked to treatment allocation. Participants were followed up for 24 weeks. The primary outcome was the difference between groups in change in WOMAC pain score from baseline to week 12, analysed in all participants who were randomly assigned and received treatment. Safety, including laboratory analyses, and pharmacokinetics from quantification of fluticasone propionate in peripheral blood were assessed in all participants who received a dose of randomly assigned treatment. A person with lived experience of knee osteoarthritis was involved in study interpretation and writing of the report. This trial is registered with ClinicalTrials.gov, NCT04120402, and the EU Clinical Trials Register, EudraCT 2021-000859-39, and is complete.</p><p><strong>Findings: </strong>Between Sept 10, 2021, and Nov 16, 2022, 1294 people were screened for eligibility, and 319 were randomly assigned to EP-104IAR (n=164) or vehicle control (n=155). One participant in the EP-104IAR group was excluded from all analyses because treatment was not administered due to an adverse event. 318 participants (135 [42%] male and 183 [58%] female, 315 [99%] White) received randomly assigned treatment and were included in the primary analysis and safety analysis (EP-104IAR, n=163; vehicle control, n=155). At week 12, least squares mean change in WOMAC pain score from baseline was -2·89 (95% CI -3·22 to -2·56) in the EP-104IAR group and -2·23 (-2·56 to -1·89) in the vehicle control group, with a between-group difference of -0·66 (-1·11 to -0·21; p=0·0044); a significant between-group difference persisted to week 14. 106 (65%) of 163 participants in the EP-104IAR group had one or more treatment-emergent adverse event compared with 89 (57%) of 155 participants in the vehicle control group. Ef","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478080","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 : 2024-10-03DOI: 10.1016/S2665-9913(24)00276-5
Xiaoyan Chen , Huifeng Shi , Barbara Wilkinson , Yuanfang Zhu
{"title":"Inclusion of pregnant populations in clinical trials in China: the ethical considerations","authors":"Xiaoyan Chen , Huifeng Shi , Barbara Wilkinson , Yuanfang Zhu","doi":"10.1016/S2665-9913(24)00276-5","DOIUrl":"10.1016/S2665-9913(24)00276-5","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142382044","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 : 2024-10-01DOI: 10.1016/S2665-9913(24)00271-6
Ameenat Lola Solebo , Salomey Kellett
{"title":"Inclusive study design to better serve the needs of children and young people with rheumatological conditions","authors":"Ameenat Lola Solebo , Salomey Kellett","doi":"10.1016/S2665-9913(24)00271-6","DOIUrl":"10.1016/S2665-9913(24)00271-6","url":null,"abstract":"","PeriodicalId":48540,"journal":{"name":"Lancet Rheumatology","volume":null,"pages":null},"PeriodicalIF":15.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376156","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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