Pub Date : 2024-10-23DOI: 10.1186/s13075-024-03408-4
Nicoletta Del Papa, Silvia Cavalli, Andrea Rindone, Francesco Onida, Giorgia Saporiti, Antonina Minniti, Maria Rosa Pellico, Claudia Iannone, Giorgia Trignani, Nicoletta D’Angelo, Manuel Sette, Raffaella Greco, Claudio Vitali, Roberto Caporali
Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT. Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy. AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function. AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.
{"title":"Long-term outcome of autologous haematopoietic stem cell transplantation in patients with systemic sclerosis: a comparison with patients treated with rituximab and with traditional immunosuppressive agents","authors":"Nicoletta Del Papa, Silvia Cavalli, Andrea Rindone, Francesco Onida, Giorgia Saporiti, Antonina Minniti, Maria Rosa Pellico, Claudia Iannone, Giorgia Trignani, Nicoletta D’Angelo, Manuel Sette, Raffaella Greco, Claudio Vitali, Roberto Caporali","doi":"10.1186/s13075-024-03408-4","DOIUrl":"https://doi.org/10.1186/s13075-024-03408-4","url":null,"abstract":"Autologous haematopoietic stem cell transplantation (AHSCT) is more effective than conventional immunosuppressive therapies (CIT) in improving the outcome of patients with rapidly progressive diffuse cutaneous systemic sclerosis (dcSSc). So far, there is still a paucity of data comparing AHSCT with rituximab (RTX). Aim of the study is to retrospectively compare, in patients with dcSSc, the effectiveness of AHSCT with that of RTX and CIT. Thirty-five dcSSc AHSCT-treated patients were compared with 29 and 36 matched cases treated with RTX and CIT, respectively. The patients were followed up for 5 years by assessing selected outcome measures every year. Overall survival, modified Rodnan skin score (mRSS), lung function tests (FVC and DLCO), and the revised EUSTAR Activity Index (REAI) were the outcome measures chosen to evaluate the therapy efficacy. AHSCT was significantly more effective than RTX and CIT in prolonging survival, inducing a rapid reduction of the mRSS and REAI and maintaining the baseline level of lung function tests for a longer time. RTX therapy was also superior to CIT in reducing REAI, mRSS and in saving lung function. AHSCT is more effective than both RTX and CIT in prolonging survival and inducing prolonged remission in patients with rapidly progressive dcSSc.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"62 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487218","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}
Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood. Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms. Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86+ pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels. In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE.
{"title":"WIF-1 contributes to lupus-induced neuropsychological deficits via the CRYAB/STAT4-SHH axis","authors":"Liping Tan, Yu Fan, Xinyi Xu, Tianshu Zhang, Xiangyu Cao, Chenghao Zhang, Jun Liang, Yayi Hou, Huan Dou","doi":"10.1186/s13075-024-03420-8","DOIUrl":"https://doi.org/10.1186/s13075-024-03420-8","url":null,"abstract":"Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood. Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms. Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86+ pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels. In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"60 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487575","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}
Pub Date : 2024-10-22DOI: 10.1186/s13075-024-03414-6
Xiaoyun Chen, Lianlian Ouyang, Sujie Jia, Ming Zhao
Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear. Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber. We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor. Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment. • SLE skin lesions show abnormal oxysterol metabolism, with fibroblasts being the main source of increased CH25H and CYP7B1 genes. • IL-1β-mediated p38 MAPK and NFκB pathways implicated in CH25H and CYP7B1 upregulation. • Enhanced PBMCs recruitment by IL-1β-stimulated fibroblasts can be attenuated by a GPR183 inhibitor, offering potential SLE skin lesion treatment.
{"title":"Oxysterols contribute to immune cell recruitment in SLE skin lesions","authors":"Xiaoyun Chen, Lianlian Ouyang, Sujie Jia, Ming Zhao","doi":"10.1186/s13075-024-03414-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03414-6","url":null,"abstract":"Abnormal oxysterol metabolism has been observed in the peripheral blood of SLE patients, but its role in systemic lupus erythematosus (SLE) skin lesions remains unclear. Targeted oxidized lipid metabolomics analysis using liquid chromatography-mass spectrometry (LC-MS) was performed to quantify oxysterols in SLE skin lesions. Immunohistochemical staining and single-cell sequencing data analysis confirmed the upregulation of oxysterol-encoding enzymes CH25H and CYP7B1. The impact on fibroblast-mediated PBMCs chemotaxis was assessed using a transwell chamber. We identified aberrant oxidized cholesterol metabolism in SLE skin lesions, characterized by elevated levels of 7-ketocholesterol, 5α-6α-cholestane-3β,5α,6β-triol, and so on. Fibroblasts were the primary cells expressing oxysterol-encoding genes, with CH25H and CYP7B1 expression upregulated via the IL-1β-mediated p38 MAPK and NFκB pathways. Notably, IL-1β-stimulated fibroblasts demonstrated enhanced PBMCs recruitment, which was attenuated by a GPR183 inhibitor. Our findings reveal a potential mechanism by which fibroblasts contribute to immune cell recruitment in SLE skin lesions by expression of CH25H and CYP7B1. This study underscores the significance of oxysterol metabolism in SLE skin lesion pathogenesis and highlights potential therapeutic targets for SLE skin lesion treatment. • SLE skin lesions show abnormal oxysterol metabolism, with fibroblasts being the main source of increased CH25H and CYP7B1 genes. • IL-1β-mediated p38 MAPK and NFκB pathways implicated in CH25H and CYP7B1 upregulation. • Enhanced PBMCs recruitment by IL-1β-stimulated fibroblasts can be attenuated by a GPR183 inhibitor, offering potential SLE skin lesion treatment.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"44 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486703","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}
Pub Date : 2024-10-22DOI: 10.1186/s13075-024-03388-5
Ruiling Feng, Xian Xiao, Bo Huang, Kai Zhang, Xia Zhang, Zhanguo Li, Yuan Jia, Jing He
Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.
{"title":"Predictive biomarkers for low-dose IL-2 therapy efficacy in systemic lupus erythematosus: a clinical analysis","authors":"Ruiling Feng, Xian Xiao, Bo Huang, Kai Zhang, Xia Zhang, Zhanguo Li, Yuan Jia, Jing He","doi":"10.1186/s13075-024-03388-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03388-5","url":null,"abstract":"Low-dose IL-2 (Ld-IL2) has shown favorable therapeutic effects in systemic lupus erythematosus (SLE) therapy. However, previous clinical trials reported an SLE Responder Index-4 (SRI-4) response rate of 65.52%-68%, with approximately half failing to achieve the primary endpoint by week 24. Our study aims to determine the real-world use of Ld-IL2 and to identify determinants of its effectiveness in SLE. We pooled data from 342 SLE patients undergoing sequential Ld-IL2 treatment, with 314 persisting for over 3 months were included in effectiveness and prediction analyses. All patients were categorized into responder (n = 136) and non-responder group (n = 178) according to SRI-4. Lupus Low Disease Activity State (LLDAS) was also analyzed to validate our results. Rash, lower complement 3 (C3), and renal involvement including urine protein, urine occult blood and urine casts emerged as prominent predictors of achieving SRI-4. Adjusting for baseline values using the ratio of change to baseline revealed significant differences in CD4 + T cell immune profiles between responders and non-responders. ROC analysis confirmed a satisfactory performance of rash, renal involvement, percentage change of CD4 + T cells, and C3 in predicting SRI-4, yielding an AUC of 0.933. LLDAS analysis showed that hematological involvements and lower CLA + Treg were potent predictive markers in LLDAS attainment. Conversely, renal involvement failed to have significant association in achieving LLDAS. The analysis of background therapy in SLE patients showed that MMF was more likely to reach the SRI-4 response with the combination of Ld-IL2. These findings uncovered the predictors of Ld-IL2 treatment efficacy in SLE patients and provided guidance to physicians for rational utilization.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"13 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486649","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}
Pub Date : 2024-10-16DOI: 10.1186/s13075-024-03410-w
Yu Zhu, Yang-Zhen Wang, Yi-tian Chen, Jie Guo, Zhen-Zhong Wang
Arthritis notably elevates mortality risk. It remains unclear whether the cardiovascular health (CVH) metrics improves the risk of all-cause mortality in patients with all types of arthritis. This study data from the National Health and Nutrition Examination Survey to probe the link between CVH and all-cause mortality among arthritis sufferers in the United States. CVH evaluation employed the Life's Essential 8 metrics. Mortality outcomes were scrutinized using Cox proportional hazard regression models. Additionally, a restricted cubic spline analysis delineated the linear relationship between CVH and mortality. The study also delved into the singular impact of each CVH component on mortality. In the cohort of 5919 patients with arthritis, improved CVH was linked to lower all-cause mortality. Specifically, each 10-point increment in CVH score was associated with a substantial decline in all-cause mortality risk [unadjusted hazard ratio (HR): 0.77, 95% Confidence Interval (95% CI): 0.71–0.83, P < 0.001]. Adjustments for age, sex, race, and social determinants of health further refined the HR to 0.72 (95% CI: 0.67–0.79, P < 0.001). Higher versus lower CVH scores at baseline markedly reduced mortality risk, with the most substantial decrease seen in those with ideal CVH metrics (HR: 0.39, 95% CI: 0.26–0.59, P < 0.001). Similar results were not observed in patients with inflammatory arthritis, but were seen in those with osteoarthritis or degenerative arthritis, and unknown types of arthritis. Ideal CVH substantially decreases all-cause mortality risk among patients with arthritis, confirming the critical role of CVH in arthritis management. This study advocates for CVH interventions as part of comprehensive arthritis treatment plans.
{"title":"Cardiovascular health metrics and all-cause mortality in osteoarthritis, inflammatory arthritis, and unclassified arthritis patients: a national prospective cohort study","authors":"Yu Zhu, Yang-Zhen Wang, Yi-tian Chen, Jie Guo, Zhen-Zhong Wang","doi":"10.1186/s13075-024-03410-w","DOIUrl":"https://doi.org/10.1186/s13075-024-03410-w","url":null,"abstract":"Arthritis notably elevates mortality risk. It remains unclear whether the cardiovascular health (CVH) metrics improves the risk of all-cause mortality in patients with all types of arthritis. This study data from the National Health and Nutrition Examination Survey to probe the link between CVH and all-cause mortality among arthritis sufferers in the United States. CVH evaluation employed the Life's Essential 8 metrics. Mortality outcomes were scrutinized using Cox proportional hazard regression models. Additionally, a restricted cubic spline analysis delineated the linear relationship between CVH and mortality. The study also delved into the singular impact of each CVH component on mortality. In the cohort of 5919 patients with arthritis, improved CVH was linked to lower all-cause mortality. Specifically, each 10-point increment in CVH score was associated with a substantial decline in all-cause mortality risk [unadjusted hazard ratio (HR): 0.77, 95% Confidence Interval (95% CI): 0.71–0.83, P < 0.001]. Adjustments for age, sex, race, and social determinants of health further refined the HR to 0.72 (95% CI: 0.67–0.79, P < 0.001). Higher versus lower CVH scores at baseline markedly reduced mortality risk, with the most substantial decrease seen in those with ideal CVH metrics (HR: 0.39, 95% CI: 0.26–0.59, P < 0.001). Similar results were not observed in patients with inflammatory arthritis, but were seen in those with osteoarthritis or degenerative arthritis, and unknown types of arthritis. Ideal CVH substantially decreases all-cause mortality risk among patients with arthritis, confirming the critical role of CVH in arthritis management. This study advocates for CVH interventions as part of comprehensive arthritis treatment plans.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"65 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440255","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}
Pub Date : 2024-10-11DOI: 10.1186/s13075-024-03411-9
Andreas Reich, Anja Weiß, Lisa Lindner, Xenofon Baraliakos, Denis Poddubnyy, Silke Zinke, Carsten Stille, Anja Strangfeld, Anne C. Regierer
<p><b>Correction: Arthritis Res Ther 25, 136 (2023)</b></p><p><b>https://doi.org/10.1186/s13075-023-03127-2</b>.</p><p>Following publication of the original article [1], the authors reported an error under the Abstract, Result sub-section.</p><p>The sentence currently reads:</p><p>In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms.</p><p>The sentence should read:</p><p>In both diagnoses, 21% of patients exhibited moderate and 8% severe depressive symptoms.</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Reich A, Weiß A, Lindner L, et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort. Arthritis Res Ther. 2023;25(1):136. https://doi.org/10.1186/s13075-023-03127-2.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>German Rheumatism Research Center (DRFZ Berlin), Epidemiology and Health Services Research, Berlin, Germany</p><p>Andreas Reich, Anja Weiß, Lisa Lindner, Denis Poddubnyy, Anja Strangfeld & Anne C. Regierer</p></li><li><p>Ruhr University Bochum, Bochum, Germany</p><p>Xenofon Baraliakos</p></li><li><p>Rheumazentrum Ruhrgebiet, Herne, Germany</p><p>Xenofon Baraliakos</p></li><li><p>Charité – Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany</p><p>Denis Poddubnyy</p></li><li><p>Berlin, Germany</p><p>Silke Zinke</p></li><li><p>Hannover, Germany</p><p>Carsten Stille</p></li><li><p>Charité – Universitätsmedizin Berlin, Berlin, Germany</p><p>Anja Strangfeld</p></li></ol><span>Authors</span><ol><li><span>Andreas Reich</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Anja Weiß</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Lisa Lindner</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xenofon Baraliakos</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Denis Poddubnyy</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Silke Zinke</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Carsten Stille</span>View author publications<p>You can also search for this author in <span>
更正：Arthritis Res Ther 25, 136 (2023)https://doi.org/10.1186/s13075-023-03127-2.Following 原文[1]发表后，作者报告了摘要中 "结果 "分节下的一个错误。该句目前的内容是：在两种诊断中，有中度抑郁症状的患者比例为8%，有重度抑郁症状的患者比例为21%。Reich A, Weiß A, Lindner L, et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort.Arthritis Res Ther.2023;25(1):136. https://doi.org/10.1186/s13075-023-03127-2.Article PubMed PubMed Central Google Scholar 下载参考文献作者和所属单位德国风湿病研究中心（DRFZ Berlin），流行病学和健康服务研究，德国柏林Andreas Reich, Anja Weiß, Lisa Lindner, Denis Poddubnyy, Anja Strangfeld & Anne C. RegiererRuhr University Bor.RegiererRuhr University Bochum, Bochum, GermanyXenofon BaraliakosRheumazentrum Ruhrgebiet, Herne, GermanyXenofon BaraliakosCharité - Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, GermanyDenis PoddubnyyBerlin, GermanySilke ZinkeHannover, GermanyCarsten StilleCharité - Universitätsmedizin Berlin, Berlin、德国Anja Strangfeld作者Andreas Reich查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Anja Weiß查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Lisa Lindner查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Xenofon Baraliakos查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者ScholarDenis PoddubnyyView 作者发表作品您也可以在 PubMed Google ScholarSilke ZinkeView 作者发表作品您也可以在 PubMed Google ScholarCarsten StilleView 作者发表作品您也可以在 PubMed Google ScholarAnja StrangfeldView 作者发表作品您也可以在 PubMed Google ScholarAnne C．RegiererView author publications您也可以在PubMed Google Scholar中搜索该作者Corresponding authorCorrespondence to Andreas Reich.出版者注释Springer Nature对出版地图中的管辖权主张和机构隶属关系保持中立。原文的在线版本可在https://doi.org/10.1186/s13075-023-03127-2.Open Access 本文采用知识共享署名 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式使用、共享、改编、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出许可使用范围，则您需要直接从版权所有者处获得许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明，否则知识共享公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文Reich, A., Weiß, A., Lindner, L. et al. Correction：抑郁症状与axSpA和PsA患者的疲劳、较差的功能状态和较少的运动参与有关：来自RABBIT-SpA队列的分析。Arthritis Res Ther 26, 177 (2024). https://doi.org/10.1186/s13075-024-03411-9Download citationPublished: 11 October 2024DOI: https://doi.org/10.1186/s13075-024-03411-9Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Correction: Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort","authors":"Andreas Reich, Anja Weiß, Lisa Lindner, Xenofon Baraliakos, Denis Poddubnyy, Silke Zinke, Carsten Stille, Anja Strangfeld, Anne C. Regierer","doi":"10.1186/s13075-024-03411-9","DOIUrl":"https://doi.org/10.1186/s13075-024-03411-9","url":null,"abstract":"<p><b>Correction: Arthritis Res Ther 25, 136 (2023)</b></p><p><b>https://doi.org/10.1186/s13075-023-03127-2</b>.</p><p>Following publication of the original article [1], the authors reported an error under the Abstract, Result sub-section.</p><p>The sentence currently reads:</p><p>In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms.</p><p>The sentence should read:</p><p>In both diagnoses, 21% of patients exhibited moderate and 8% severe depressive symptoms.</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Reich A, Weiß A, Lindner L, et al. Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort. Arthritis Res Ther. 2023;25(1):136. https://doi.org/10.1186/s13075-023-03127-2.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><h3>Authors and Affiliations</h3><ol><li><p>German Rheumatism Research Center (DRFZ Berlin), Epidemiology and Health Services Research, Berlin, Germany</p><p>Andreas Reich, Anja Weiß, Lisa Lindner, Denis Poddubnyy, Anja Strangfeld & Anne C. Regierer</p></li><li><p>Ruhr University Bochum, Bochum, Germany</p><p>Xenofon Baraliakos</p></li><li><p>Rheumazentrum Ruhrgebiet, Herne, Germany</p><p>Xenofon Baraliakos</p></li><li><p>Charité – Universitätsmedizin Berlin, Department of Gastroenterology, Infectiology and Rheumatology, Berlin, Germany</p><p>Denis Poddubnyy</p></li><li><p>Berlin, Germany</p><p>Silke Zinke</p></li><li><p>Hannover, Germany</p><p>Carsten Stille</p></li><li><p>Charité – Universitätsmedizin Berlin, Berlin, Germany</p><p>Anja Strangfeld</p></li></ol><span>Authors</span><ol><li><span>Andreas Reich</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Anja Weiß</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Lisa Lindner</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xenofon Baraliakos</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Denis Poddubnyy</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Silke Zinke</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Carsten Stille</span>View author publications<p>You can also search for this author in <span>","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"3 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405218","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}
Pub Date : 2024-10-11DOI: 10.1186/s13075-024-03406-6
Beatrice Bergström, Tilia Selldén, Miriam Bollmann, Mattias N. D. Svensson, Anna-Karin Hultgård Ekwall
Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators. Primary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations. Six thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages. MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.
{"title":"Methotrexate promotes the release of granulocyte–macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling","authors":"Beatrice Bergström, Tilia Selldén, Miriam Bollmann, Mattias N. D. Svensson, Anna-Karin Hultgård Ekwall","doi":"10.1186/s13075-024-03406-6","DOIUrl":"https://doi.org/10.1186/s13075-024-03406-6","url":null,"abstract":"Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators. Primary RA-FLS were activated by stimulation with interleukin-1β (IL-1β) or platelet-derived growth factor + IL-1β in the presence or absence of MTX or TOFA, with or without additional inhibitors. Co-cultures of synovial cells were performed in direct and indirect systems. Cells were collected for RNA sequencing or qPCR, and supernatants were analyzed for protein concentrations. Six thousand three hundred fifty genes were differentially expressed, the majority being upregulated, in MTX-treated activated RA-FLS and 970 genes, the majority being downregulated, in TOFA-treated samples. Pathway analysis showed that MTX had largest effects on ‘Molecular mechanisms of cancer’ and TOFA on ‘Interferon signaling’. Targeted analysis of disease-associated genes revealed that MTX increased the expression of cell cycle-regulating genes but also of pro-inflammatory mediators like IL-1α (IL1A) and granulocyte–macrophage colony-stimulating factor, GM-CSF (CSF2). The MTX-promoted expression of CSF2 in activated RA-FLS peaked at 48 h, could be mediated via either NF-κB or AP-1 transcription factors, and was abrogated by IL-1 inhibitors (IRAK4 inhibitor and anakinra). In a co-culture setting, MTX-treatment of activated RA-FLS induced IL1B expression in macrophages. MTX treatment induces secretion of IL-1 from activated RA-FLS which by autocrine signaling augments their release of GM-CSF. This unexpected effect of MTX might contribute to the persistence of synovitis.\u0000","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"2 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405220","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}
Pub Date : 2024-10-10DOI: 10.1186/s13075-024-03409-3
Jenna M. Schulz, Trevor B. Birmingham, Holly T. Philpott, C. Thomas Appleton, Hayden F. Atkinson, J. Robert Giffin, Frank Beier
Mechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition. Twenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times. Decreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03–0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]). Decreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.
{"title":"Changes and associations between synovial fluid and magnetic resonance imaging markers of osteoarthritis after high tibial osteotomy","authors":"Jenna M. Schulz, Trevor B. Birmingham, Holly T. Philpott, C. Thomas Appleton, Hayden F. Atkinson, J. Robert Giffin, Frank Beier","doi":"10.1186/s13075-024-03409-3","DOIUrl":"https://doi.org/10.1186/s13075-024-03409-3","url":null,"abstract":"Mechanobiological mechanisms of osteoarthritis (OA) are unclear. Our objectives were to explore: 1) changes in knee joint physiology using a large panel of synovial fluid biomarkers from before to one year after high tibial osteotomy (HTO) surgery, and 2) the association of changes in the synovial fluid biomarkers with the changes in MRI measures of knee effusion-synovitis and articular cartilage composition. Twenty-six patients with symptomatic knee OA and varus alignment underwent synovial fluid aspirations and 3 T MRI before and one year after medial opening wedge HTO. Cytokine and growth factor levels in synovial fluid were measured with multiplex assays. Ontology and pathway enrichment was assessed using data protein sets with gene set enrichment analysis (GSEA), and analyzed using linear mixed effects models. MRIs were analyzed for effusion-synovitis and T2 cartilage relaxation time using manual segmentations. Changes in biomarker concentrations were correlated to changes in MRI effusion-synovitis volume and articular cartilage T2 relaxation times. Decreased enrichment in Toll-like receptor and TNF-α signalling was detected one year after HTO. The leading contributors to this reduction included IL-6, TNF-α and IL-1β, whereas the highest contributors to positive enrichment were EGF, PDGF-BB and FGF-2. Effusion-synovitis volume decreased (mean [95%CI]) one year after HTO (-2811.58 [-5094.40, -528.76mm3]). Effusion-synovitis volume was moderately correlated (r [95% CI]) with decreased MMP-1 (0.44 [0.05; 0.71]), IL-7 (0.41 [0.00; 0.69]) and IL-1β (0.59 [0.25; 0.80]) and increased MIP-1β (0.47 [0.10; 0.73]). Medial tibiofemoral articular cartilage T2 relaxation time decreased (mean [95% CI]) one year after HTO (-0.33 [-2.69; 2.05]ms). Decreased T2 relaxation time was moderately correlated to decreased Flt-3L (0.61 [0.28; 0.81]), IL-10 (0.47 [0.09; 0.73]), IP-10 (0.42; 0.03–0.70) and increased MMP-9 (-0.41 [-0.7; -0.03]) and IL-18 (-0.48 [-0.73; -0.10]). Decreased aberrant knee mechanical loading in patients with OA is associated with decreased biological and imaging measures of inflammation (measured in synovial fluid and on MRI) and increased anabolic processes. These exploratory findings suggest that improvement in knee loading can produce long-term (one year) improvement in joint physiology.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"70 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398058","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}
Pub Date : 2024-10-08DOI: 10.1186/s13075-024-03407-5
Vasileios Georgopoulos, Stephanie Smith, Daniel F. McWilliams, Eamonn Ferguson, Richard Wakefield, Dorothy Platts, Susanne Ledbury, Deborah Wilson, David A. Walsh
Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by ‘static’ (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and ‘dynamic’ (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman’s correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.
{"title":"Contribution of inflammation markers and quantitative sensory testing (QST) indices of central sensitisation to rheumatoid arthritis pain","authors":"Vasileios Georgopoulos, Stephanie Smith, Daniel F. McWilliams, Eamonn Ferguson, Richard Wakefield, Dorothy Platts, Susanne Ledbury, Deborah Wilson, David A. Walsh","doi":"10.1186/s13075-024-03407-5","DOIUrl":"https://doi.org/10.1186/s13075-024-03407-5","url":null,"abstract":"Pain, the primary complaint in rheumatoid arthritis (RA), is multifaceted, and may be driven by inflammatory disease activity and central sensitisation. We aimed to ascertain what proportion of RA pain severity is explained by markers of inflammation and quantitative sensory testing (QST) indices of central sensitisation. This was a cross-sectional analysis of data from individuals with clinically active RA. Pain severity was assessed using numerical rating scales and inflammation via 28-joint Disease Activity Score (DAS28) and Ultrasound (Greyscale, Power Doppler). Pain sensitivity was assessed by ‘static’ (tibialis anterior or brachioradialis pressure pain detection threshold-PPT-TA/PPT-BR) and ‘dynamic’ (temporal summation-TS, conditioned pain modulation-CPM) QST. Bivariate associations used Spearman’s correlation coefficients, and multivariable linear regression models determined relative contributions to pain severity. In bivariate analyses of N = 96 (age 65 ± 10y, 77% females) people with RA, pain severity was significantly associated with inflammation indices (r = 0.20 to 0.55), and CPM (r=-0.26). In multivariable models that included TS, CPM, age, sex, and body mass index, inflammation indices remained significantly associated with pain severity. Multivariable models explained 22 to 27% of pain variance. Heterogeneity was apparent for associations with pain between subscores for pain now, strongest or average over the past 4-weeks. In individuals with clinically active RA, markers of inflammatory disease activity best explain RA pain with only marginal contributions from QST indices of central sensitisation. Although inflammation plays a key role in the experience of RA pain, the greater proportion of pain severity remains unexplained by DAS28 and ultrasound indices of inflammation.","PeriodicalId":8419,"journal":{"name":"Arthritis Research & Therapy","volume":"5 1","pages":""},"PeriodicalIF":4.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384161","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}
Pub Date : 2024-10-04DOI: 10.1186/s13075-024-03405-7
Oh Chan Kwon, Hye Sun Lee, So Young Jeon, Min-Chan Park
Patients with radiographic axial spondyloarthritis (r-axSpA) are at increased risk of incident cardiovascular events. Tumor necrosis factor inhibitors (TNFi) have shown a protective effect against incident cardiovacular events. However, the incidence of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events, and the effect of TNFi on recurrent cardiovascular events remain unclear. We aimed to assess the incidence rate of recurrent cardiovascular events in patients with r-axSpA with a history of cardiovascular events and evaluate the effect of TNFi on the risk of recurrent cardiovascular events. This nationwide cohort study used data from the Korean National Claims Database. Data of patients with r-axSpA who had a history of cardiovascular events after being diagnosed with r-axSpA were extracted from the database. The outcome of interest was the recurrence of cardiovascular events (myocardial infarction or stroke). Patients were followed from the index date (date of the first cardiovascular event) to the date of cardiovascular event recurrence, the last date with claims data, or December 31, 2021, whichever occured first. The incidence rate of recurrent cardiovascular events was calculated. An inverse probability weighted Cox model was used to assess the effect of TNFi exposure on the risk of recurrent cardiovascular events. This study included 413 patients (TNFi non-exposure, n = 338; TNFi exposure, n = 75). The incidence rate of recurrent cardiovascular events was 32 (95% confidence interval [CI] 22–42) per 1,000 person-years (TNFi non-exposure, 36 [95% CI 24–48] per 1,000 person-years; TNFi exposure, 19 [95% CI 2–35] per 1,000 person-years). In the inverse probability weighted Cox model, TNFi exposure was significantly associated with a lower risk of recurrent cardiovascular events (hazard ratio 0.33, 95% CI 0.12–0.94). The incidence rate of recurrent cardiovascular events in patients with r-axSpA is substantial. TNFi exposure was associated with a lower risk of recurrent cardiovascular events.
放射性轴性脊柱关节炎（r-axSpA）患者发生心血管事件的风险增加。肿瘤坏死因子抑制剂（TNFi）对心血管事件有保护作用。然而，在有心血管事件病史的r-axSpA患者中，复发性心血管事件的发生率以及TNFi对复发性心血管事件的影响仍不清楚。我们旨在评估有心血管事件病史的r-axSpA患者的复发性心血管事件发生率，并评估TNFi对复发性心血管事件风险的影响。这项全国性队列研究使用的数据来自韩国国家索赔数据库。研究人员从数据库中提取了确诊为r-axSpA后曾发生过心血管事件的r-axSpA患者的数据。关注的结果是心血管事件（心肌梗死或中风）的复发。对患者的随访从指数日期（首次心血管事件发生日期）开始，到心血管事件复发日期、最后一次有索赔数据的日期或 2021 年 12 月 31 日（以先发生者为准）为止。计算心血管事件复发率。采用逆概率加权Cox模型评估TNFi暴露对心血管事件复发风险的影响。该研究共纳入413例患者（未暴露于TNFi，338例；暴露于TNFi，75例）。复发性心血管事件的发病率为每千人年32例（95%置信区间[CI] 22-42）（TNFi非暴露，每千人年36例[95% CI 24-48]；TNFi暴露，每千人年19例[95% CI 2-35]）。在逆概率加权Cox模型中，TNFi暴露与较低的复发性心血管事件风险显著相关（危险比为0.33，95% CI为0.12-0.94）。r-axSpA患者复发心血管事件的发生率很高。TNFi暴露与较低的复发性心血管事件风险相关。
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