Guy Katz, Cory Perugino, Zachary S Wallace, Bohang Jiang, Thomas Guy, Grace A McMahon, Isha Jha, Yuqing Zhang, Hang Liu, Ana D Fernandes, Shiv S Pillai, John Patterson Atkinson, Alfred Hyoungju Kim, John H Stone
Objectives: Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.
Methods: We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia.
Results: Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia.
Conclusions: Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology.
目的:低补体血症常见于 IgG4 相关疾病(IgG4-RD)患者。我们旨在确定与低补体血症相关的 IgG4-RD 特征,并研究这种疾病的补体激活机制:我们对符合IgG4-RD分类标准的279名患者进行了单中心横断面研究,使用未调整和多变量调整的逻辑回归来确定与低补体血症相关的因素:结果:90 例(32%)患者出现低补体血症。在未调整模型中,受累器官的数量(OR 1.42,95% CI 1.23 至 1.63)和受累淋巴结(OR 3.87,95% CI 2.19 至 6.86)、肺(OR 3.81,95% CI 2.10至6.89)、胰腺(OR 1.66,95% CI 1.001至2.76)、肝脏(OR 2.73,95% CI 1.17至6.36)和肾脏(OR 2.48,95% CI 1.47至4.18)分别与低补体血症相关。在对年龄、性别和受累器官数量进行调整后,只有淋巴结(OR 2.59,95% CI 1.36 至 4.91)和肺(OR 2.56,95% CI 1.35 至 4.89)受累仍与低补体血症相关,而肾脏受累的相关性减弱(OR 1.6,95% CI 0.92 至 2.98)。在调整分析中,纤维化疾病表现(OR 0.43,95% CI 0.21 至 0.87)和泪腺受累(OR 0.53,95% CI 0.28 至 0.999)与低补体血症呈反比关系。低补体血症与较高的所有 IgG 亚类和 IgE 浓度有关(所有 p 结论:IgG4-RD 中的低补体血症并非肾脏受累患者所独有,它可能反映了疾病的程度。IgG1 与 IgG4-RD 中的低补体血症有独立的相关性,但 IgG4 则没有。补体激活可能与 IgG4-RD 的病理生理学有关。
{"title":"Multiorgan involvement and circulating IgG1 predict hypocomplementaemia in IgG4-related disease.","authors":"Guy Katz, Cory Perugino, Zachary S Wallace, Bohang Jiang, Thomas Guy, Grace A McMahon, Isha Jha, Yuqing Zhang, Hang Liu, Ana D Fernandes, Shiv S Pillai, John Patterson Atkinson, Alfred Hyoungju Kim, John H Stone","doi":"10.1136/ard-2024-225846","DOIUrl":"https://doi.org/10.1136/ard-2024-225846","url":null,"abstract":"<p><strong>Objectives: </strong>Hypocomplementaemia is common in patients with IgG4-related disease (IgG4-RD). We aimed to determine the IgG4-RD features associated with hypocomplementaemia and investigate mechanisms of complement activation in this disease.</p><p><strong>Methods: </strong>We performed a single-centre cross-sectional study of 279 patients who fulfilled the IgG4-RD classification criteria, using unadjusted and multivariable-adjusted logistic regression to identify factors associated with hypocomplementaemia.</p><p><strong>Results: </strong>Hypocomplementaemia was observed in 90 (32%) patients. In the unadjusted model, the number of organs involved (OR 1.42, 95% CI 1.23 to 1.63) and involvement of the lymph nodes (OR 3.87, 95% CI 2.19 to 6.86), lungs (OR 3.81, 95% CI 2.10 to 6.89), pancreas (OR 1.66, 95% CI 1.001 to 2.76), liver (OR 2.73, 95% CI 1.17 to 6.36) and kidneys (OR 2.48, 95% CI 1.47 to 4.18) were each associated with hypocomplementaemia. After adjusting for age, sex and number of organs involved, only lymph node (OR 2.59, 95% CI 1.36 to 4.91) and lung (OR 2.56, 95% CI 1.35 to 4.89) involvement remained associated with hypocomplementaemia while the association with renal involvement was attenuated (OR 1.6, 95% CI 0.92 to 2.98). Fibrotic disease manifestations (OR 0.43, 95% CI 0.21 to 0.87) and lacrimal gland involvement (OR 0.53, 95% CI 0.28 to 0.999) were inversely associated with hypocomplementaemia in the adjusted analysis. Hypocomplementaemia was associated with higher concentrations of all IgG subclasses and IgE (all p<0.05). After adjusting for serum IgG1 and IgG3, only IgG1 but not IgG4 remained strongly associated with hypocomplementaemia.</p><p><strong>Conclusions: </strong>Hypocomplementaemia in IgG4-RD is not unique to patients with renal involvement and may reflect the extent of disease. IgG1 independently correlates with hypocomplementaemia in IgG4-RD, but IgG4 does not. Complement activation is likely involved in IgG4-RD pathophysiology.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854586","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}
Alekhya Amudalapalli, Sandeep Nagar, Rasmi Ranjan Sahoo, Ashlesha Shukla, Abhichandra Maddineni, Adya Kinkar Panda, Pradeepta Patro
{"title":"Mystery of hidden pearls: bursitis in the shoulder.","authors":"Alekhya Amudalapalli, Sandeep Nagar, Rasmi Ranjan Sahoo, Ashlesha Shukla, Abhichandra Maddineni, Adya Kinkar Panda, Pradeepta Patro","doi":"10.1136/ard-2024-226359","DOIUrl":"https://doi.org/10.1136/ard-2024-226359","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141854587","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}
Lieve Van Hoovels, Liesbeth E Bakker-Jonges, Dina Vara, Caroline Bijnens, Lucy Studholme, Daniela Sieghart, Bert Vander Cruyssen, Patrick Verschueren, Guenter Steiner, Jan G M C Damoiseaux, Xavier Bossuyt
{"title":"New WHO ACPA standard enables standardisation among anti-CCP2 assays, but not other ACPA assays using different antigens.","authors":"Lieve Van Hoovels, Liesbeth E Bakker-Jonges, Dina Vara, Caroline Bijnens, Lucy Studholme, Daniela Sieghart, Bert Vander Cruyssen, Patrick Verschueren, Guenter Steiner, Jan G M C Damoiseaux, Xavier Bossuyt","doi":"10.1136/ard-2024-226169","DOIUrl":"https://doi.org/10.1136/ard-2024-226169","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750898","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}
Objectives: Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK.
Methods: VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments.
Results: Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients.
Conclusions: VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.
目的:动脉壁炎症和重塑是高安氏动脉炎(TAK)的特征。有人认为,血管平滑肌细胞(VSMC)是炎症损伤的主要靶细胞,并参与了 TAK 的动脉重塑。血管平滑肌细胞是否积极参与了动脉壁炎症尚未得到阐明。研究表明,组织中的细胞衰老与局部炎症的持续存在密切相关。我们旨在研究 VSMCs 衰老是否导致血管炎症以及 TAK 中的前衰老因子:方法:通过组织学检查、大样本RNA-Seq和单细胞RNA-Seq检测TAK患者血管手术样本中的VSMCs衰老和衰老相关分泌表型。在一系列体外和体内实验中研究了关键的前衰老因子及其下游信号通路:组织学发现、原代细胞培养和转录组分析表明,TAK 患者的血管内皮细胞具有早衰特征,并通过上调与衰老相关的炎性细胞因子的表达,在很大程度上导致了血管炎症。研究发现,IL-6是促使TAK患者VSMC衰老和衰老相关线粒体功能障碍的关键细胞因子。从机理上讲,IL-6诱导的磷酸化STAT3(Tyr705)的非典型线粒体定位阻止了丝裂霉素2(MFN2)的蛋白酶体降解,进而促进了衰老相关的线粒体功能障碍和VSMCs衰老。抑制线粒体STAT3或MFN2可改善TAK患者体外培养动脉中VSMCs的衰老:结论:VSMCs呈现出细胞衰老的特征,并积极参与TAK患者的血管炎症。血管IL-6-线粒体STAT3-MFN2信号是VSMC衰老的重要驱动因素。
{"title":"Association between premature vascular smooth muscle cells senescence and vascular inflammation in Takayasu's arteritis.","authors":"Chenglong Fang, Lihong Du, Shang Gao, Yuexin Chen, Zuoguan Chen, Zhiyuan Wu, Lili Li, Jing Li, Xiaofeng Zeng, Mengtao Li, Yongjun Li, Xinping Tian","doi":"10.1136/ard-2024-225630","DOIUrl":"10.1136/ard-2024-225630","url":null,"abstract":"<p><strong>Objectives: </strong>Arterial wall inflammation and remodelling are the characteristic features of Takayasu's arteritis (TAK). It has been proposed that vascular smooth muscle cells (VSMCs) are the main targeted cells of inflammatory damage and participate in arterial remodelling in TAK. Whether VSMCs are actively involved in arterial wall inflammation has not been elucidated. Studies have shown that cellular senescence in tissue is closely related to local inflammation persistence. We aimed to investigate whether VSMCs senescence contributes to vascular inflammation and the prosenescent factors in TAK.</p><p><strong>Methods: </strong>VSMCs senescence and senescence-associated secretory phenotype were detected by histological examination, bulk RNA-Seq and single-cell RNA-seq conducted on vascular surgery samples of TAK patients. The key prosenescent factors and the downstream signalling pathway were investigated in a series of in vitro and ex vivo experiments.</p><p><strong>Results: </strong>Histological findings, primary cell culture and transcriptomic analyses demonstrated that VSMCs of TAK patients had the features of premature senescence and contributed substantially to vascular inflammation by upregulating the expression of senescence-associated inflammatory cytokines. IL-6 was found to be the critical cytokine that drove VSMCs senescence and senescence-associated mitochondrial dysfunction in TAK. Mechanistically, IL-6-induced non-canonical mitochondrial localisation of phosphorylated STAT3 (Tyr705) prevented mitofusin 2 (MFN2) from proteasomal degradation, and subsequently promoted senescence-associated mitochondrial dysfunction and VSMCs senescence. Mitochondrial STAT3 or MFN2 inhibition ameliorated VSMCs senescence in ex vivo cultured arteries of TAK patients.</p><p><strong>Conclusions: </strong>VSMCs present features of cellular senescence and are actively involved in vascular inflammation in TAK. Vascular IL-6-mitochondrial STAT3-MFN2 signalling is an important driver of VSMCs senescence.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178721","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}
Edward K L Chan, K Michael Pollard, Marvin J Fritzler
{"title":"Eng Meng Tan.","authors":"Edward K L Chan, K Michael Pollard, Marvin J Fritzler","doi":"10.1136/ard-2024-226025","DOIUrl":"10.1136/ard-2024-226025","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141236571","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}
Kamini E Kuchinad, Ji Soo Kim, Adrianne Woods, Gwen Leatherman, Laura Gutierrez-Alamillo, Maureen D Mayes, Robyn Domsic, Paula S Ramos, Richard M Silver, John Varga, Lesley Ann Saketkoo, Suzanne Kafaja, Victoria K Shanmugan, Jessica Gordon, Lorinda Chung, Elana J Bernstein, Pravitt Gourh, Francesco Boin, Daniel L Kastner, Scott L Zeger, Livia Casciola-Rosen, Fredrick M Wigley, Ami A Shah
Objective: To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.
Methods: 803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared.
Results: Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%.
Conclusions: This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.
{"title":"Racial variability in immune responses only partially explains differential systemic sclerosis disease severity.","authors":"Kamini E Kuchinad, Ji Soo Kim, Adrianne Woods, Gwen Leatherman, Laura Gutierrez-Alamillo, Maureen D Mayes, Robyn Domsic, Paula S Ramos, Richard M Silver, John Varga, Lesley Ann Saketkoo, Suzanne Kafaja, Victoria K Shanmugan, Jessica Gordon, Lorinda Chung, Elana J Bernstein, Pravitt Gourh, Francesco Boin, Daniel L Kastner, Scott L Zeger, Livia Casciola-Rosen, Fredrick M Wigley, Ami A Shah","doi":"10.1136/ard-2023-225458","DOIUrl":"10.1136/ard-2023-225458","url":null,"abstract":"<p><strong>Objective: </strong>To understand if autoantibodies account for racial variation in disease severity, we compared autoantibody distribution and associated phenotype between self-identified black and white systemic sclerosis (SSc) patients.</p><p><strong>Methods: </strong>803 black and 2178 white SSc patients had systematic testing for autoantibodies using Euroimmun (centromere (ACA), RNA-polymerase III (POLR3), Scl70, PM/Scl, NOR90, Th/To, Ku, U3RNP and Ro52) and commercial ELISA (U1RNP). In this observational study, logistic regression was performed to assess the association between self-identified race and outcomes, adjusting for autoantibodies. To estimate whether the effect of race was mediated by autoantibody status, race coefficients from multivariate models including and excluding autoantibodies were compared.</p><p><strong>Results: </strong>Anti-Scl70, anti-U1RNP, anti-U3RNP, anti-Th/To, anti-Ku and anti-NOR90 were more common in the black cohort than in the white cohort, which was enriched for ACA, anti-POLR3 and anti-PM/Scl. Black individuals had a higher prevalence of severe Raynaud's, skin, lung, gastrointestinal and renal disease whereas white individuals had a higher prevalence of severe heart and muscle disease. Adjusting for autoantibodies decreased the effect of race on outcome for telangiectasias, forced vital capacity <70%, pulmonary hypertension and severe lung, heart, muscle and gastrointestinal disease by 11%-44% and increased the association between race and renal crisis and severe kidney disease by 37%-52%.</p><p><strong>Conclusions: </strong>This study is the largest systematic analysis of autoantibody responses in a geographically diverse population of black SSc patients. Black and white individuals with SSc have distinct autoantibody profiles. Autoantibodies explain only a fraction of the effect of race on clinical outcomes, suggesting other factors contribute to disparate outcomes between these groups.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632466","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}
Elise van Mulligen, Maureen Rutten-van Mölken, Annette van der Helm-van Mil
Objective: Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis.
Methods: Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs.
Results: Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (β=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, β=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (β=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices.
Conclusion: When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs.
目的:早期诊断和开始治疗是类风湿关节炎(RA)的关键所在,但对于早期诊断与晚期诊断的经济效益却从未进行过调查。我们的目的是研究与晚期诊断相比,早期诊断 RA 是否会降低治疗相关费用:研究对象为 2011 年至 2017 年间连续纳入莱顿早期关节炎诊所的 RA 患者(431 人)。症状持续时间定义为从症状出现到首次到门诊就诊的时间;早期治疗开始时间定义为症状持续时间:在自身抗体阴性的RA患者中,晚期治疗组的费用比早期治疗组高316%(β=4.16(95% CI 1.57至11.1);4856欧元对1159欧元)。如果采用2012年的价格,结果类似。对于自身抗体阳性的RA患者,晚期组的费用高出19%(9418欧元对7934欧元,β=1.19,0.57对2.47)。如果采用2012年的价格,这一影响依然存在,但幅度较小。在使用生物制剂的自身抗体阳性的RA患者中,治疗开始晚与46%的高成本相关(β=1.46(0.91至2.33));如果使用2012年的价格,成本也会更高:结论:如果在症状出现后12周内发现RA,自身抗体阴性和自身抗体阳性RA的治疗相关费用均较低。这项研究首次报告了早期诊断和治疗对治疗相关费用的影响。
{"title":"Early identification of rheumatoid arthritis: does it induce treatment-related cost savings?","authors":"Elise van Mulligen, Maureen Rutten-van Mölken, Annette van der Helm-van Mil","doi":"10.1136/ard-2024-225746","DOIUrl":"https://doi.org/10.1136/ard-2024-225746","url":null,"abstract":"<p><strong>Objective: </strong>Early diagnosis and treatment-start is key for rheumatoid arthritis (RA), but the economic effect of an early versus a later diagnosis has never been investigated. We aimed to investigate whether early diagnosis of RA is associated with lower treatment-related costs compared with later diagnosis.</p><p><strong>Methods: </strong>Patients with RA consecutively included in the Leiden Early Arthritis Clinic between 2011 and 2017 were studied (n=431). Symptom duration was defined as the time between symptom onset and first presentation at the outpatient clinic; early treatment start was defined as symptom duration <12 weeks. Information on disease-modifying anti-rheumatic drug use per patient over 5 years was obtained from prescription data from patient records. Prices were used from 2022 and 2012 (proxy of time of prescription) to study the impact of changes in drug costs. Autoantibody-positive and autoantibody-negative RA were studied separately because differences in disease severity may influence costs.</p><p><strong>Results: </strong>Within autoantibody-negative RA, costs were 316% higher in the late compared with the early group (β=4.16 (95% CI 1.57 to 11.1); €4856 vs €1159). When using 2012 prices, results were similar. For autoantibody-positive RA, costs were 19% higher in the late group (€9418 vs €7934, β=1.19, 0.57 to 2.47). This effect was present but smaller when using 2012 prices. Within patients with autoantibody-positive RA using biologicals, late treatment start was associated with 46% higher costs (β=1.46 (0.91 to 2.33)); higher costs were also seen when using 2012 prices.</p><p><strong>Conclusion: </strong>When RA is detected within 12 weeks after symptom onset, treatment-related costs were lower in both autoantibody-negative and autoantibody-positive RA. This study is the first to report how early diagnosis and treatment start impact treatment-related costs.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632465","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}
Esperanza Naredo, Maria Antonietta D'Agostino, Lene Terslev, Carlos Pineda, M Isabel Miguel, Joan Blasi, George A Bruyn, Marion C Kortekaas, Peter Mandl, Rodina Nestorova, Marcin Szkudlarek, Plamen Todorov, Violeta Vlad, Priscilla Wong, Catherine Bakewell, Emilio Filippucci, Alen Zabotti, Mihaela Micu, Florentin Vreju, Mohamed Mortada, José Alexandre Mendonça, Carlos A Guillen-Astete, Otto Olivas-Vergara, Annamaria Iagnocco, Petra Hanova, Ilaria Tinazzi, Peter V Balint, Sibel Zehra Aydin, David Kane, Helen Keen, Gurjit S Kaeley, Ingrid Möller
Objectives: The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system.
Methods: The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis.
Results: 32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39-0.71) and intraobserver reliability good to excellent (κ 0.80-0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes).
Conclusions: We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.
{"title":"Validation and incorporation of digital entheses into a preliminary GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis.","authors":"Esperanza Naredo, Maria Antonietta D'Agostino, Lene Terslev, Carlos Pineda, M Isabel Miguel, Joan Blasi, George A Bruyn, Marion C Kortekaas, Peter Mandl, Rodina Nestorova, Marcin Szkudlarek, Plamen Todorov, Violeta Vlad, Priscilla Wong, Catherine Bakewell, Emilio Filippucci, Alen Zabotti, Mihaela Micu, Florentin Vreju, Mohamed Mortada, José Alexandre Mendonça, Carlos A Guillen-Astete, Otto Olivas-Vergara, Annamaria Iagnocco, Petra Hanova, Ilaria Tinazzi, Peter V Balint, Sibel Zehra Aydin, David Kane, Helen Keen, Gurjit S Kaeley, Ingrid Möller","doi":"10.1136/ard-2023-225278","DOIUrl":"10.1136/ard-2023-225278","url":null,"abstract":"<p><strong>Objectives: </strong>The main objective was to generate a GLobal OMERACT Ultrasound DActylitis Score (GLOUDAS) in psoriatic arthritis and to test its reliability. To this end, we assessed the validity, feasibility and applicability of ultrasound assessment of finger entheses to incorporate them into the scoring system.</p><p><strong>Methods: </strong>The study consisted of a stepwise process. First, in cadaveric specimens, we identified enthesis sites of the fingers by ultrasound and gross anatomy, and then verified presence of entheseal tissue in histological samples. We then selected the entheses to be incorporated into a dactylitis scoring system through a Delphi consensus process among international experts. Next, we established and defined the ultrasound components of dactylitis and their scoring systems using Delphi methodology. Finally, we tested the interobserver and intraobserver reliability of the consensus- based scoring systemin patients with psoriatic dactylitis.</p><p><strong>Results: </strong>32 entheses were identified in cadaveric fingers. The presence of entheseal tissues was confirmed in all cadaveric samples. Of these, following the consensus process, 12 entheses were selected for inclusion in GLOUDAS. Ultrasound components of GLOUDAS agreed on through the Delphi process were synovitis, tenosynovitis, enthesitis, subcutaneous tissue inflammation and periextensor tendon inflammation. The scoring system for each component was also agreed on. Interobserver reliability was fair to good (κ 0.39-0.71) and intraobserver reliability good to excellent (κ 0.80-0.88) for dactylitis components. Interobserver and intraobserver agreement for the total B-mode and Doppler mode scores (sum of the scores of the individual abnormalities) were excellent (interobserver intraclass correlation coefficient (ICC) 0.98 for B-mode and 0.99 for Doppler mode; intraobserver ICC 0.98 for both modes).</p><p><strong>Conclusions: </strong>We have produced a consensus-driven ultrasound dactylitis scoring system that has shown acceptable interobserver reliability and excellent intraobserver reliability. Through anatomical knowledge, small entheses of the fingers were identified and histologically validated.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140292499","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}
Yasuhiro Katsumata, Eisuke Inoue, Masayoshi Harigai, Jiacai Cho, Worawit Louthrenoo, Alberta Hoi, Vera Golder, Chak Sing Lau, Aisha Lateef, Yi-Hsing Chen, Shue-Fen Luo, Yeong-Jian Jan Wu, Laniyati Hamijoyo, Zhanguo Li, Sargunan Sockalingam, Sandra Navarra, Leonid Zamora, Yanjie Hao, Zhuoli Zhang, Madelynn Chan, Shereen Oon, Kristine Ng, Jun Kikuchi, Tsutomu Takeuchi, Fiona Goldblatt, Sean O'Neill, Nicola Tugnet, Annie Hui Nee Law, Sang-Cheol Bae, Yoshiya Tanaka, Naoaki Ohkubo, Sunil Kumar, Rangi Kandane-Rathnayake, Mandana Nikpour, Eric F Morand
Objectives: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE).
Methods: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.
Results: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.
Conclusions: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.
{"title":"Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study.","authors":"Yasuhiro Katsumata, Eisuke Inoue, Masayoshi Harigai, Jiacai Cho, Worawit Louthrenoo, Alberta Hoi, Vera Golder, Chak Sing Lau, Aisha Lateef, Yi-Hsing Chen, Shue-Fen Luo, Yeong-Jian Jan Wu, Laniyati Hamijoyo, Zhanguo Li, Sargunan Sockalingam, Sandra Navarra, Leonid Zamora, Yanjie Hao, Zhuoli Zhang, Madelynn Chan, Shereen Oon, Kristine Ng, Jun Kikuchi, Tsutomu Takeuchi, Fiona Goldblatt, Sean O'Neill, Nicola Tugnet, Annie Hui Nee Law, Sang-Cheol Bae, Yoshiya Tanaka, Naoaki Ohkubo, Sunil Kumar, Rangi Kandane-Rathnayake, Mandana Nikpour, Eric F Morand","doi":"10.1136/ard-2023-225369","DOIUrl":"10.1136/ard-2023-225369","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred.</p><p><strong>Results: </strong>Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day.</p><p><strong>Conclusions: </strong>In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":null,"pages":null},"PeriodicalIF":20.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995416","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}