RMD Open最新文献

{"title":"Colchicine enhances macrophage cholesterol efflux by targeting DTL-mediated ubiquitination and degradation of ABCA1.","authors":"Lingfei Tong, Wenming Wu, Yan Wang, Lihua Duan, Hui Li","doi":"10.1136/rmdopen-2025-006553","DOIUrl":"10.1136/rmdopen-2025-006553","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to elucidate the potential pharmacological mechanisms by which colchicine confers clinical benefits in patients with atherosclerotic cardiovascular disease, focusing on its effects on cholesterol efflux.</p><p><strong>Methods: </strong>This study was conducted in multiple cellular models. First, cell viability was assessed and the optimal dosage of colchicine was screened via the Cell Counting Kit-8 assay. Subsequently, Oil Red O staining, commercial kit detection and Boron dipyrromethene (BODIPY) -cholesterol labelling were employed to analyse intracellular lipid accumulation, foam cell formation and cholesterol efflux rate in macrophages, respectively. Furthermore, molecular docking and transcriptome sequencing were performed to explore the potential therapeutic targets and underlying mechanisms of colchicine, followed by a series of cellular experiments (quantitative reverse transcription-PCR, ATP-binding cassette transporter A1 (ABCA1) degradation analysis, plasmid construction and transfection, co-immunoprecipitation, immunoblotting) for comprehensive validation of the identified potential mechanisms.</p><p><strong>Results: </strong>In the present study, we demonstrate that colchicine markedly promotes cholesterol efflux, a key process that reverses macrophage foam cell formation and consequently contributes to its cardioprotective effects. We identified modulation of the ubiquitination of ABCA1 as the pivotal mechanism by which colchicine enhances cholesterol efflux. Our findings reveal for the first time that denticleless E3 ubiquitin protein ligase homologue (DTL) functions as a crucial E3 ligase in this regulatory pathway. Mechanistically, colchicine suppresses DTL expression and disrupts its interaction with ABCA1, leading to increased ABCA1 protein stability, enhanced ABCA1-mediated cholesterol efflux and a subsequent reduction in foam cell formation.</p><p><strong>Conclusion: </strong>Colchicine shows great promise for drug repurposing as a novel therapeutic agent. Its strong capacity to reverse foam cell formation highlights its potential to extend clinical use beyond gout management to cardiovascular secondary prevention.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13347924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148412664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and assessment of an assisted diagnosis model using machine learning for identifying adult-onset Still's disease in fever of unknown origin: a retrospective study in China.","authors":"Jian Liu, Jia Chen, Xuelin He, Yongquan Dong, Yu Tian, Yuqing Jin, Huiyao Sun, Jingsong Li, Yunqing Qiu","doi":"10.1136/rmdopen-2025-006462","DOIUrl":"10.1136/rmdopen-2025-006462","url":null,"abstract":"<p><strong>Background: </strong>Adult-onset Still's disease (AOSD) is a systemic autoinflammatory disorder lacking a gold-standard diagnostic criterion.</p><p><strong>Objective: </strong>To develop and validate a clinically applicable model for identifying AOSD among patients with fever of unknown origin (FUO) who have clinical suspicion for AOSD.</p><p><strong>Methods: </strong>Clinical data (2010-2020) were divided into training and internal test set (7:3) using stratified random sampling according to disease status (AOSD vs non-AOSD). Feature selection was performed using Boruta, recursive feature elimination and least absolute shrinkage and selection operator algorithms. Selected features were used to train logistic regression (LR), random forest and extreme gradient boosting models with fivefold cross-validation. Model performance was evaluated using area under the curve (AUC), receiver operating characteristic curves, sensitivity, specificity and accuracy. External validation was performed at another centre using the same adjudication procedure.</p><p><strong>Results: </strong>A total of 847 patients were included, comprising a derivation cohort of 771 patients and an independent external validation cohort of 75 patients. Six features-age, neutrophil percentage, white blood cell count, infection indicator, ferritin and 'AOSD-related clinical presentation score'-were consistently selected by at least two algorithms and used to build the model. LR achieved the highest AUC in both training (0.969; 95% CI 0.956 to 0.983) and test sets (0.960; 95% CI 0.934 to 0.985). A nomogram based on the LR model demonstrated good real-world performance in the independent validation cohort, with an AUC of 0.906.</p><p><strong>Conclusions: </strong>We developed a machine learning model using electronic medical records to identify AOSD among patients with FUO with clinical suspicion for AOSD. The model shows high accuracy and potential for early identification of AOSD in this specific clinical setting.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucocorticoid in giant cell arteritis: real-world treatment patterns over time and associated burden in a nationwide hospital-based study within the French health insurance database.","authors":"Maxime Beydon, Diane Lacaille, Bruno Fautrel, Raphaèle Seror, David Hajage, Florence Tubach","doi":"10.1136/rmdopen-2026-006866","DOIUrl":"10.1136/rmdopen-2026-006866","url":null,"abstract":"<p><strong>Objective: </strong>Recent advances in giant cell arteritis (GCA) management aim to reduce glucocorticoid (GC). We described changes in treatment patterns over time in real life and assessed associations between cumulative GC use and adverse outcomes.</p><p><strong>Methods: </strong>This retrospective population-based study used the French national health insurance database (Système National des Données de Santé) and included 18 301 incident GCA cases between 2010 and 2022. Latent class growth modelling identified GC use trajectories. We described trends in cumulative dose and sparing agent use. Multivariable survival models assessed factors associated with sustained GC-free remission and association between GC cumulative exposure and mortality, serious infections, major adverse cardiovascular events (MACE) and osteoporotic fractures.</p><p><strong>Results: </strong>Four GC use trajectories were identified. Two high-dose trajectories declined over time. Yet, mean 2-year cumulative GC dose remained high, reaching 7.6 g among patients diagnosed in 2022. Methotrexate use increased until 2020 and plateaued thereafter while tocilizumab prescriptions rose, reaching over 25% in 2022. Male sex and baseline methotrexate or tocilizumab use were associated with faster GC tapering, while age >75 years, hypertension, kidney and neurodegenerative diseases were associated with slower tapering. Each gram of GC was associated with higher mortality (HR per gram 1.024, 95% CI 1.021 to 1.027). Yearly cumulative exposure to doses ≤5 mg/day was associated with increased infection (HR 1.13, 95% CI 1.00 to 1.29) and MACE (HR 1.04, 95% CI 1.01 to 1.08).</p><p><strong>Conclusion: </strong>Despite reductions in high-dose use, cumulative GC exposure in GCA remains substantial and associated with adverse outcomes, even at the lowest doses.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148405840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anifrolumab, a potential treatment for ADA2 deficiency.","authors":"Loris Vincenti, Jonathan Sormani, Alexandre Belot, Maël Richard, Yoann Roubertou, Natacha Grienay-Poletto, Anne Perrine Foray, Anaïs Nombel, Isabelle Durieu, Quitterie Reynaud","doi":"10.1136/rmdopen-2025-006569","DOIUrl":"10.1136/rmdopen-2025-006569","url":null,"abstract":"<p><p>Adenosine deaminase 2 deficiency (DADA2) is an inborn error of immunity leading to systemic vasculitis, haematological manifestations, immune deficiency and/or autoimmunity. We report the case of a 26-year-old female with an initial diagnosis of systemic lupus erythematosus (SLE). However, atypical evolution patterns for SLE (hypogammaglobulinaemia, moderate B-cell lymphopenia, disappearance of anti-dsDNA) led to the identification of a homozygous class 5 missense variant of CECR1/ADA2, thus to a final diagnosis of DADA2. Strikingly, the patient was treated with anifrolumab (an anti-interferon alpha receptor 1 antibody) that rapidly induced clinical remission and significant corticosteroid tapering. Consistently, we show a lower type I interferon (IFN-I) score and a persistently low tumour necrosis factor α (TNFα) and IL-6 expression levels in whole blood cells of the patient during anifrolumab compared to anti-TNFα. Altogether, this case (1) illustrates the challenging diagnosis of DADA2 (SLE with hypogammaglobulinaemia) and (2) reinforces DADA2 as a disease at the border with type I interferonopathies. Besides, we report here, to our knowledge, the first description of a successful use of anifrolumab in DADA2, paving the way for further studies to validate this therapeutic approach.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between SARS-CoV-2 booster vaccination and hospitalisation and/or death due to COVID-19 in adults with immune-mediated inflammatory diseases: nested case-control study using linked primary-care, hospitalisation and mortality data from England.","authors":"Niraj S Kukreja, Georgina Nakafero, Abhishek Abhishek","doi":"10.1136/rmdopen-2026-006834","DOIUrl":"10.1136/rmdopen-2026-006834","url":null,"abstract":"<p><strong>Objectives: </strong>To assess the association between COVID-19 booster vaccination and hospitalisation and/or death due to COVID-19 among adults with immune-mediated inflammatory diseases (IMIDs).</p><p><strong>Methods: </strong>Adults with IMIDs prescribed steroid-sparing immune-suppressing drugs in Clinical Practice Research Datalink Aurum linked to hospitalisation and mortality records were included. Cases were hospitalised for or died due to COVID-19. Controls were risk-set matched to cases. Exposures were number of COVID-19 booster vaccinations between 16 September 2021 and 13 March 2023; receipt of autumn 2021, spring 2022, autumn 2022 boosters; and time since last booster. Multivariable logistic regression was used. Adjusted OR (aOR) and 95% CIs and adjusted vaccine effectiveness (1 - aORs × 100%) were calculated.</p><p><strong>Results: </strong>We included 2178 cases and 17 750 controls (mean age 65.5 years; 60.2% women). Hospitalisation and/or death due to COVID-19 was negatively associated with receipt of three (aOR (95% CI) 0.20 (0.15 to 0.28)), two (aOR (95% CI) 0.29 (0.23 to 0.36)) or one booster (aOR (95% CI) 0.56 (0.48 to 0.65), respectively, compared with no booster. The aOR (95% CI) across the booster cycles were: autumn 2021 (aOR (95% CI) 0.40 (0.32 to 0.50)), spring 2022 (aOR (95% CI) 0.52 (0.42 to 0.65)) and autumn 2022 (aOR (95% CI) 0.33 (0.25 to 0.43)). Hospitalisation and/or death due to COVID-19 was negatively associated with booster vaccination within 365 days compared with no booster vaccination. There was no statistically significant association for boosters received more than 365 days ago.</p><p><strong>Conclusions: </strong>COVID-19 booster vaccination was associated with fewer hospitalisation and/or death due to COVID-19 among adults with IMIDs. These findings support regular booster vaccination in this high-risk population.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343080/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond genotype: clustering analysis highlights clinical heterogeneity in paediatric familial Mediterranean fever.","authors":"Isild Mahé, Claire Billard, Federica Anselmi, Linda Rossi-Semerano, Caroline Galeotti, Isabelle Kone-Paut, Perrine Dusser","doi":"10.1136/rmdopen-2026-006764","DOIUrl":"10.1136/rmdopen-2026-006764","url":null,"abstract":"<p><strong>Background: </strong>Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in the <i>MEFV</i> gene. Despite therapeutic advances with colchicine and interleukin-1 (IL-1) inhibitors, FMF shows marked interindividual variability, including among symptomatic heterozygotes, challenging genotype-phenotype correlations.</p><p><strong>Objectives: </strong>To identify clinically meaningful subgroups of paediatric patients with FMF using a clustering approach and to characterise their clinical features and disease trajectories.</p><p><strong>Methods: </strong>We conducted a monocentric retrospective study including 185 paediatric patients diagnosed with FMF between 2004 and 2025 according to Eurofever criteria. Patients were stratified as genetically confirmed FMF (homozygous, compound heterozygous) or symptomatic heterozygotes. Demographic, clinical, laboratory and treatment data were collected longitudinally. Clustering analysis was used to identify clinically meaningful subgroups.</p><p><strong>Results: </strong>The median age at onset was 2.5 years and the median diagnostic delay was 24 months. Ninety-three (50%) patients were symptomatic heterozygotes. Compared with genetically confirmed FMF, heterozygotes had milder disease, lower colchicine doses and less frequent IL-1 inhibitor use. Cluster analysis identified five distinct subgroups, ranging from asymptomatic or mild heterozygotes without treatment to early-onset homozygous patients with severe disease requiring higher-dose colchicine and IL-1 inhibitors. Not all heterozygous patients had a mild disease course. Sex, age at onset, genotype, attack frequency and inflammatory markers contributed to cluster differentiation. Severe phenotypes were enriched in female patients with early-onset M694V homozygosity.</p><p><strong>Conclusion: </strong>Cluster analysis identified heterogeneous patterns of disease expression, suggesting that the genotype alone does not fully explain clinical variability in FMF. These findings highlight the value of multidimensional approaches to better characterise disease heterogeneity.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belimumab outperforms placebo for attainment of modified DORIS remission and LLDAS without the glucocorticoid component: a post hoc analysis of five phase III SLE trials.","authors":"Ioannis Parodis, Julius Lindblom, Roger A Levy, Alexander Tsoi, Margherita Zen, Dionysis Nikolopoulos, Munther Khamashta, Ryan Tomlinson, Anca Askanase, Ronald van Vollenhoven, Mandana Nikpour","doi":"10.1136/rmdopen-2025-006624","DOIUrl":"10.1136/rmdopen-2025-006624","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate Definition Of Remission In SLE (DORIS) and Lupus Low Disease Activity State (LLDAS) attainment with belimumab versus placebo in a dataset of pooled phase III clinical trials in systemic lupus erythematosus (SLE) using modified definitions that excluded the glucocorticoid (GC) component ('non-GC-DORIS' and 'non-GC-LLDAS') as the trials lacked mandated GC tapering protocols.</p><p><strong>Methods: </strong>In this post hoc analysis, data of adults with SLE receiving belimumab (10 mg/kg/month intravenously or 200 mg/week subcutaneously) or placebo plus standard therapy were pooled from five clinical trials (BLISS-76 (NCT00410384), BLISS-52 (NCT00424476), North East Asia (NCT01345253), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241)). Non-GC-DORIS and non-GC-LLDAS attainment rates (calculated based on SLE Disease Activity Index 2000 and Physician's Global Assessment only) with belimumab versus placebo were compared up to week 52 in the overall population and in patient subgroups of interest.</p><p><strong>Results: </strong>Non-GC-DORIS and non-GC-LLDAS attainment at week 52 were significantly higher with belimumab (n=1869) versus placebo (n=1217; non-GC-DORIS: 18% vs 13%, risk ratio, RR (95% CI): 1.44 (1.20 to 1.71); p<0.001; non-GC-LLDAS: 32% vs 21%, RR (95% CI): 1.50 (1.32 to 1.71); p<0.001). Similar results were observed across most analysed patient subgroups; at week 52, differences were generally greater in the high versus low disease activity subgroups and Asian and White subgroups exhibited significantly higher attainment with belimumab versus placebo.</p><p><strong>Conclusion: </strong>Belimumab was associated with higher attainment of DORIS remission and LLDAS excluding the GC component versus placebo; attainment rates were approximately twofold higher than those previously reported using the full definitions.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of sarcopenia in patients with rheumatoid arthritis: a cross-sectional study.","authors":"Huijuan Wang, Jiaoya Xu, Yunshen Li, Yiming Shi, Yaxin Cheng, Yixin Zheng, Chenyang Song, Fuyu Zhao, Yu Shan, Qiang Ji, Xiaoyu Xiong, Xin Peng, Minrui Liang, Dongyi He","doi":"10.1136/rmdopen-2026-006945","DOIUrl":"10.1136/rmdopen-2026-006945","url":null,"abstract":"<p><strong>Objective: </strong>Sarcopenia, defined by reductions in muscle mass and strength, increases the risk of adverse outcomes in patients with rheumatoid arthritis (RA)-driven in part by chronic inflammation-and is linked to a poor prognosis. This study aimed to investigate the prevalence of sarcopenia in patients with RA using Asian Working Group for Sarcopenia (AWGS) 2025 criteria and to analyse its associated clinical features.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 978 patients with RA (mean age 60.1±12.1 years, range 21-99 years and 86.4% female) diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria. Sarcopenia was diagnosed based on the AWGS 2025 consensus, using bioelectrical impedance analysis for appendicular skeletal muscle mass index, handgrip dynamometry for muscle strength. Demographic data, clinical parameters and medication use were collected. Statistical analysis was performed using SPSS V.21.0.</p><p><strong>Results: </strong>The overall prevalence of sarcopenia among patients with RA was 18.6% (182/978). Male gender (OR 9.140, 95% CI 5.211 to 16.029), body mass index (BMI) (OR 0.586, 95% CI 0.534 to 0.643), disease duration (OR 1.046, 95% CI 1.025 to 1.069), rheumatoid factor (RF)-IgM level (OR 1.002, 95% CI 1.000 to 1.003), prednisone dosage (OR 1.094, 95% CI 1.033 to 1.159), tumour necrosis factor inhibitors (TNF-i) use (OR 0.502, 95% CI 0.312 to 0.808) and tocilizumab use (OR 0.493, 95% CI 0.304 to 0.799) were associated with sarcopenia in patients with RA.</p><p><strong>Conclusion: </strong>The prevalence of sarcopenia is considerable in patients with RA. Key risk factors include male gender, lower BMI, longer disease duration, higher RF-IgM level and higher dosage of glucocorticoid use. The use of tocilizumab and TNF-i may be associated with a reduced incidence of sarcopenia in this population.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treat-to-target strategies are feasible in elderly-onset rheumatoid arthritis given its reassuring risk-benefit profile.","authors":"Hamit Harun Dag, Marloes G B van Onna, Radboud J E M Dolhain, Pascal H P de Jong","doi":"10.1136/rmdopen-2026-007055","DOIUrl":"10.1136/rmdopen-2026-007055","url":null,"abstract":"<p><strong>Objective: </strong>To compare 2-year pharmacotherapy needs and adverse events (AEs) profiles between patients with elderly-onset rheumatoid arthritis (EORA) and young-onset RA (YORA) under a treat-to-target (T2T) strategy with a fixed medication protocol.</p><p><strong>Methods: </strong>Data from the treatment in the Rotterdam Early Arthritis cohort trial, a multicentre randomised controlled study, were analysed. Patients with RA (1987/2010 criteria) were classified as EORA (>65 years) or YORA (18-65 years). Disease Activity Score based on 44 swollen and 53 tender joint counts (DAS44) trajectories, active disease and sustained remission were assessed using mixed-effects models. Protocol-guided disease-modifying antirheumatic drug (DMARD) and glucocorticoid (GC) use, difficult-to-treat (D2T) RA prevalence and AEs were evaluated descriptively. Cox proportional hazards models examined time to first biologic (b)DMARD initiation, bDMARD survival and DMARD-free remission.</p><p><strong>Results: </strong>Among 425 patients with RA, 98 (23%) had EORA (mean age 73 years, SD 5) and 327 (77%) had YORA (mean age 48 years, SD 11). Patients with EORA were more often male (50% vs 28%) and had more comorbidities (76% vs 49%). DAS44 trajectories were similar (mean difference 0.03, 95% CI -0.13 to 0.18), but EORA had less often active disease (OR 0.8, 95% CI 0.4 to 1.5) and more often sustained remission (OR 1.5, 95% CI 0.6 to 3.4). bDMARD initiation rate was lower and slower in EORA than YORA (28% vs 38%; HR 0.7, 95% CI 0.4 to 1). First bDMARD survival and GC use were comparable. D2T-RA was rare (EORA 2% vs YORA 6%) and treatment adjustments due to AEs were similar (43% vs 47%).</p><p><strong>Conclusion: </strong>A T2T approach is feasible and effective in EORA, given its reassuring risk-benefit profile, while recognising the need for individualised management.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles exposing complement split products are associated with kidney involvement in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).","authors":"Anna Juto, Jelena Colic, Apostolos Taxiarchis, Iva Pruner, Vivianne Malmström, Annette Bruchfeld, Iva Gunnarsson, Aleksandra Antovic","doi":"10.1136/rmdopen-2025-006468","DOIUrl":"10.1136/rmdopen-2025-006468","url":null,"abstract":"<p><strong>Background: </strong>The complement system is crucial in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) pathogenesis. Extracellular vesicles (EVs) serve as carriers of bioactive substances, influencing the immune system. We aimed to investigate myeloperoxidase-positive EVs (MPO⁺EVs) exposing complement components (C3a, C4d), terminal complement complex (TCC) and complement factor B (CFB) in relation to disease activity and kidney involvement.</p><p><strong>Methods: </strong>Plasma MPO⁺EVs carrying complement products, C3a, C4d, TCC or CFB, were analysed by flow cytometry. Clinical data, including kidney biopsy findings, were retrieved. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS).</p><p><strong>Results: </strong>Eighty-one patients with AAV with granulomatosis with polyangiitis (n=59) or microscopic polyangiitis (n=22) were included. Active disease was noted in 73 (90.1%) patients and 50 (68.5%) had kidney involvement. Patients with kidney involvement had higher concentrations of MPO⁺, MPO⁺C3a⁺, MPO⁺C4d⁺ and MPO⁺TCC⁺EVs compared to patients without, and concentrations correlated positively with BVAS (p<0.05), respectively. Levels of EVs showed a negative correlation with estimated glomerular filtration rate, and a positive correlation with the proportions of necrosis and crescents in kidney biopsies. ROC curve analysis indicated that MPO⁺EVs could distinguish patients with kidney involvement from non-renal AAV. A binary multivariable logistic regression confirmed an independent association between levels of EV subsets and kidney involvement.</p><p><strong>Conclusions: </strong>Elevated levels of MPO⁺EVs exposing complement components in patients with kidney involvement indicate activation of the classical or lectin and common complement pathways in renal AAV. Furthermore, the association between levels of MPO⁺EVs with the presence of crescents and necrotic lesions in kidney tissue supports a role in renal inflammatory activity.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13343100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}