Annals of the Rheumatic Diseases最新文献

{"title":"Spatial transcriptomic analysis of muscle biopsy from patients with treatment-naive juvenile dermatomyositis reveals mitochondrial abnormalities despite disease-related interferon-driven signature.","authors":"Aris E Syntakas, Melissa Kartawinata, Nia M L Evans, Huong D Nguyen, Charalampia Papadopoulou, Muthana Al Obaidi, Clarissa Pilkington, Yvonne Glackin, Christopher B Mahony, Adam P Croft, Simon Eaton, Mario Cortina-Borja, Olumide Ogunbiyi, Ashirwad Merve, Lucy R Wedderburn, Meredyth G Ll Wilkinson","doi":"10.1016/j.ard.2025.07.015","DOIUrl":"10.1016/j.ard.2025.07.015","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the spatial transcriptomic landscape of muscle tissue from patients with treatment-naive juvenile dermatomyositis (JDM) in comparison to healthy paediatric muscle tissue.</p><p><strong>Methods: </strong>Muscle biopsies from 3 patients with JDM and 3 age-matched controls were analysed using the Nanostring GeoMx Digital Spatial Profiler. Regions of interest were selected based on muscle fibres without immune cells, immune cell infiltration and CD68+ macrophage enrichment. Differential gene expression, pathway analysis and pathways clustering analysis were conducted. Key findings were validated in 19 cases of JDM using immunohistochemistry and chemical stains, and a bulk RNAseq dataset of 4 cases of JDM.</p><p><strong>Results: </strong>JDM muscle tissues exhibited significant interferon pathway activation and mitochondrial dysfunction compared to controls. A 15-gene interferon signature was significantly elevated in JDM muscle and macrophage-enriched regions, correlating with clinical weakness. In contrast, mitochondrial dysregulation, characterised by downregulated respiratory chain pathways, was present regardless of interferon activity or muscle strength. The interferon-driven and mitochondrial signatures were replicated in an independent RNAseq dataset from JDM muscle; the lack of association between interferon signature and mitochondrial dysregulation was validated in 19 cases by conventional staining methods. Clustering analysis revealed distinct transcriptomic profiles between JDM and control tissues, as well as between patients with JDM with varying clinical phenotypes.</p><p><strong>Conclusions: </strong>This study highlights mitochondrial dysfunction as a consistent pathological feature in JDM muscle, which may be independent of interferon-driven inflammation. These findings highlight the potential for mitochondrial-targeted therapies in JDM management and emphasise the need for further studies to explore their therapeutic value.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1706-1720"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815730","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}

{"title":"Mycophenolate mofetil plus methotrexate versus cyclophosphamide with sequential azathioprine for treatment of Takayasu arteritis.","authors":"Xiaochuan Sun, Jing Li, Xinwang Duan, Yahong Wang, Yu Chen, Ying Wang, Liyun Zhang, Dongyun Yao, Jing Xue, Zhenbiao Wu, Yi Zhao, Li Luo, Hongfeng Zhang, Xiuling Zhang, Lili Pan, Xiaofeng Zeng, Mengtao Li, Peter A Merkel, Xinping Tian","doi":"10.1016/j.ard.2025.07.018","DOIUrl":"10.1016/j.ard.2025.07.018","url":null,"abstract":"<p><strong>Objectives: </strong>Study the efficacy and safety of mycophenolate mofetil (MMF) combined with methotrexate (MTX) compared to cyclophosphamide (CYC) followed by azathioprine (AZA) to treat active Takayasu arteritis (TAK).</p><p><strong>Methods: </strong>Adults with active TAK were randomised in a 2:1 ratio to receive oral MMF plus MTX or intravenous CYC followed by oral AZA. All subjects also received high-dose oral glucocorticoids with a predefined taper. The primary endpoint was overall response rate at week 52, defined as achieving a complete response (CR) or partial response (PR). Secondary endpoints included rates of CR and PR at weeks 28 and 52.</p><p><strong>Results: </strong>A total of 111 patients with TAK were enrolled: 74 in the MMF+MTX group and 37 in the CYC/AZA group, with comparable baseline demographic and clinical features. The overall response rates at 28 and 52 weeks were 58.1% and 55.4% in the MMF+MTX group, respectively, higher than 32.4% at both time points in the CYC/AZA group (P = .011 and .022). CR and PR rates at 28 and 52 weeks were also higher in the MMF+MTX group. Relapse occurred in 4 patients in the MMF+MTX group and 2 in the CYC/AZA group. One serious adverse event, neutropenia with fever, occurred in 1 patient in the CYC/AZA group.</p><p><strong>Conclusions: </strong>Treatment of active TAK with MMF+MTX has more favourable efficacy compared to CYC/AZA. These findings provide evidence to use the combination of MTX and MMF, 2 generally well-tolerated and inexpensive therapies, to treat TAK.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1733-1742"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940130","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}

{"title":"In immune-mediated necrotising myopathy, anti-HMGCR antibodies inhibit HMGCR activity, leading to the sarcoplasmic accumulation of lipid droplets and myofibres necrosis.","authors":"Margherita Giannini, Giulia Quiring, Mustapha Oulad-Abdelghani, Béatrice Lannes, Yves Allenbach, Olivier Benveniste, Olivier Boyer, Aleksandra Nadaj Pakleza, Bernard Geny, Alain Meyer","doi":"10.1016/j.ard.2025.04.027","DOIUrl":"10.1016/j.ard.2025.04.027","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1752-1755"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131788","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}

{"title":"EULAR recommendations for a core dataset to support clinical care and translational and observational research in systemic lupus erythematosus.","authors":"Johanna Mucke, George Bertsias, Martin Aringer, Laurent Arnaud, Carina Boström, Ricard Cervera, Gamal Chehab, László Czirják, Lene Wohlfahrt Dreyer, Luís Inês, Søren Jacobsen, Charite Kjaerside Nielsen, Emiliano Marasco, Marta Mosca, Kirsi Myllys, Cristina Pamfil, Jose M Pego-Reigosa, Jutta G Richter, Savino Sciascia, Farah Tamirou, Michel Tsang-A-Sjoe, Edward M Vital, Ronald Van Vollenhoven, Chris Wincup, Matthias Schneider","doi":"10.1016/j.ard.2025.07.001","DOIUrl":"10.1016/j.ard.2025.07.001","url":null,"abstract":"<p><strong>Objectives: </strong>To enhance clinical and multicentre research outcomes in systemic lupus erythematosus (SLE), standardised documentation of patient- and disease-related features is important. The aim of this European Alliance of Associations for Rheumatology (EULAR) taskforce was to define a core set of essential items for the comprehensive care of SLE patients in clinical practice, with an extension for vital elements required for translational and observational research.</p><p><strong>Methods: </strong>A multidisciplinary EULAR task force group engaged in a multistep approach including a 4-round Delphi survey and a face-to-face meeting.</p><p><strong>Results: </strong>Twenty-five stakeholders from 14 different countries participated. During the process, the initial list of 99 items was reduced to 73 items for inclusion in the clinical core dataset and 8 additional items for research extension. The items were grouped in the domains 'general', 'disease activity', 'disease history', 'disease damage', 'comorbidities', 'patient reported outcomes', 'laboratory markers', 'outcomes', and 'treatment', with suggested frequencies of assessment.</p><p><strong>Conclusions: </strong>The presented clinical core dataset and its research extension are designed to improve SLE patient care and facilitate collaborative research by ensuring the comparability of datasets and cohort descriptions. This initiative lays the foundation for the establishment of a global SLE data space and has the potential to expedite the implementation of personalised medicine in SLE care.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":"1621-1631"},"PeriodicalIF":20.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144940096","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}

{"title":"Response to correspondence about our article Hernández-Cruz B, Otero-Varela L, Freire-González M, Busquets-Pérez N, García González AJ, Moreno-Ramos M, et al. Janus kinase inhibitors and tumour necrosis factor inhibitors show a favourable safety profile and similar persistence in rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: real-world data from the BIOBADASER registry. Ann Rheum Dis. 2024 Aug 27;83(9):1189-99. doi:10.1136/ard-2023-225271.","authors":"Blanca Hernández-Cruz","doi":"10.1016/j.ard.2025.08.022","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.022","url":null,"abstract":"","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205479","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}

{"title":"Short-chain fatty acids and their gut microbial pathways distinguish rheumatoid arthritis in discordant monozygotic twins.","authors":"Rebecca B Blank, Kevin Bu, Xinyuan Zhang, Weixi Chen, Ian Cunningham, Jeremy Sokolove, Lauren Lahey, Adriana Heguy, Rhina Medina, Carles Ubeda, Renuka R Nayak, Jiyuan Hu, Adam Cantor, Jakleen Lee, Frances M K Williams, Jose C Clemente, Jose U Scher","doi":"10.1016/j.ard.2025.08.029","DOIUrl":"10.1016/j.ard.2025.08.029","url":null,"abstract":"<p><strong>Objectives: </strong>Although genetic risk factors, such as HLA-DRB1 alleles, contribute to the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other factors are involved in disease development. Further, the relative contribution of nongenetic elements in identical twins has not been characterised. Here, we aimed to characterise host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multiomics approach.</p><p><strong>Methods: </strong>Eight pairs of MZ twins discordant for RA (N = 16) were enrolled in the United States (US). The gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and plasma proteins were measured in both plasma and faeces. Levels of short-chain fatty acids (SCFAs) from serum and faeces were quantified using gas chromatography mass spectrometry (GC-MS). Metagenomic data from a UK twin registry (TwinsUK) (N = 14) were used to validate findings in the US population.</p><p><strong>Results: </strong>Although microbiome diversity and composition did not differ between twins, we observed a significant decrease in the SCFA-producing bacteria Blautia faecis and significantly lower concentrations of faecal butyrate and propionate in affected RA twins in the US. TwinsUK showed a similar reduction in the SCFA-producers Gemmiger formicilis and Faecalicatena fissicatena, as well as bacterial SCFA metabolism pathways.</p><p><strong>Conclusions: </strong>Multiomics biomarkers differentiate MZ twins discordant for RA. Faecal butyrate and propionate, as well as SCFA-producing bacteria, were decreased in affected twins. We found a similar decrease in SCFA-producing taxa in affected twins in a geographically distinct cohort in the UK. Our results suggest that, if further validated in larger cohorts, multiomics approaches may improve our understanding of RA pathogenesis and, potentially, contribute to more accurate diagnostics and coadjuvant therapies.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197937","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}

{"title":"The likelihood of joint inflammation recurrence in previously affected joints during psoriatic arthritis disease course.","authors":"Mark Berman, Ori Elkayam, Dafne Capelusnik","doi":"10.1016/j.ard.2025.08.020","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.020","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the likelihood of joint inflammation recurrence in previously affected joints during the disease course of psoriatic arthritis, and to identify joint-specific predictors associated with recurrence risk using real-world data.</p><p><strong>Methods: </strong>Patients with PsA followed at the Tel Aviv Medical Center Rheumatology Institute were included. At each visit, the 68-swollen joint count (SJC68) was assessed. The association between baseline joint swelling and recurrence was analysed using mixed-effects logistic regression, adjusting for joint location and for follow-up visit. An interaction analysis was conducted to determine the association of each joint location.</p><p><strong>Results: </strong>A total of 492 patients were included, with a median of 6 (IQR 4-9) follow-up visits. Of these, 44% were male, with a mean age at baseline of 48 y/o (SD 15), and a mean disease duration of 1 year (1.9). At baseline, 420 (85%) patients had at least 1 swollen joint, with a median SJC68 of 2 (1-5). Among the 33,456 joints assessed, 1402 were swollen at baseline (4.2%), and 514 (36.7%) of them recurred during follow-up. Mixed-effect logistic regression showed that baseline swelling predicted future swelling (odds ratio 2.88, 95% CI 2.61-3.18) with variation by joint location. This association was not modified by sex, age, or disease duration.</p><p><strong>Conclusions: </strong>This study identified a strong association between baseline joint swelling and subsequent swelling episodes in patients with PsA. This association varied by joint and remained significant when limited to the most frequently swollen joints.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172617","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}

{"title":"Development and validation of a Disease Activity index for PSoriatic Arthritis based on 44 joints (DAPSA44).","authors":"Dafne Capelusnik, Clementina Lopez-Medina, Désirée van der Heijde, Daniel Aletaha, Josef Smolen, Anna Molto, Sofia Ramiro","doi":"10.1016/j.ard.2025.08.027","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.027","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to develop a modified Disease Activity index for PSoriatic Arthritis (DAPSA) score using the 44-joint count instead of the 66 swollen/68 tender joint counts (SJC/TJC) in patients with spondyloarthritis (SpA) (axial SpA [axSpA], peripheral SpA [pSpA], and psoriatic arthritis [PsA]) and evaluate its construct validity.</p><p><strong>Methods: </strong>Patients with axSpA, pSpA, and PsA included in the Assessment of SpondyloArthritis international Society-PerSpA (PERipheral involvement in SpondyloArthritis) study were randomly allocated 1:2 stratified for diagnosis and country into a derivation and validation cohort. For all patients, the 66SJC/68TJC were available, from which the SJC44/TJC44 were extracted. The derivation cohort was used to calculate the conversion factors for SJC66/TJC68 into SJC44/TJC44 to obtain the DAPSA44 using mixed-effects linear regression models. The validation cohort assessed the DAPSA44 construct validity through the agreement between continuous original-DAPSA/DAPSA44 (intraclass correlation coefficient [ICC]) and DAPSA disease activity states (weighted-kappa), Bland-Altman plot, Spearman correlations between original-DAPSA/DAPSA44 and external constructs, and discrimination between known groups (standardised mean differences [SMDs]) after stratifying patients into active/inactive based on a combination of patient global assessment (≥5/<5) and SJC (≥1/0 or ≥2/<2).</p><p><strong>Results: </strong>A total of 4121 patients (65% axSpA, 10% pSpA, and 25% PsA) were included. Conversion factors from the derivation cohort (n = 1364) for TJC and SJC were 1.30 and 1.34, respectively. The validation cohort (n = 2757) analyses showed almost-perfect agreement between original-DAPSA and DAPSA44 (ICC 0.98, kappa 0.95). Spearman correlation coefficients between DAPSA44 and external constructs fell within the predefined 0.3-wide range of corresponding original-DAPSA coefficients. DAPSA44 demonstrated excellent discriminatory ability (SMD > 0.8) across all scenarios of active/inactive disease.</p><p><strong>Conclusions: </strong>These findings support the use of DAPSA44 as a comparable tool to the original DAPSA for assessing disease activity due to peripheral arthritis in SpA, especially in situations where only a reduced joint count is available.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172627","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}

{"title":"Augmentation of immunothrombosis as a key mechanism underlying JAK inhibition associated hypercoagulability in rheumatoid arthritis.","authors":"Paula David, Tom Macleod, Ala Altaie, Yu Shi, Kerem Abacar, Sami Giryes, Gabrielle de Mello Santos, Payal Ganguly, Mark Harland, Chi Wong, Andrew Scarsbrook, Paul Emery, Kulveer Mankia, Shouvik Dass, Andrea Di Matteo, Benazir Saleem, Cédric Duval, Robert Ariëns, Dennis McGonagle","doi":"10.1016/j.ard.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.ard.2025.09.002","url":null,"abstract":"<p><strong>Objectives: </strong>Venous thromboembolism (VTE), following Janus kinase inhibitors treatment (JAKi), is poorly understood in rheumatoid arthritis (RA). We investigated whether JAKi augmented immune cell-driven clotting or immunothrombosis in RA.</p><p><strong>Methods: </strong>Peripheral blood leukocytes (PBLs) isolated from patients with RA and healthy controls were treated with various JAKi classes, before stimulation with Toll-like receptor (TLR)-4 (lipopolysaccharide [LPS]) or TLR3 (polyinosinic-polycytidylic acid-poly (I:C)) agonists. Conditioned supernatants were used in plasma turbidity assays to evaluate clot formation and lysis dynamics, while bulk RNA sequencing, enzyme-linked immunosorbent assay, and bead-based immunoassays were used to explore immunothrombosis mechanisms.</p><p><strong>Results: </strong>Turbidity analyses showed that conditioned media from PBLs treated with LPS and tofacitinib significantly accelerated clot formation when compared to LPS alone, and this effect was tissue factor pathway dependent and accompanied by elevations in immunothrombotic cytokines, including tumour necrosis factor α, interleukin (IL)-1β, and IL-6. PBLs from patients with active RA exhibited significantly greater immunothrombotic potential compared to those with low disease activity, despite comparable baseline cytokine levels. RNA sequencing analysis revealed significant pathway enrichment in tofacitinib/LPS-treated PBLs, including activation of Nuclear Factor (NF)-κB pathways, increased tissue factor expression, and reduced levels of anticoagulant factors such as protein S. Pharmacological inhibition assays with 5 JAK therapies suggested that JAK1/tyrosine kinase 2-dependent effect underscored increased thrombosis but selective JAK3 inhibition did not reproduce the prothrombotic effects. Finally, patients with RA with JAK-associated pulmonary embolism showed interstitial changes compatible with immunothrombosis in 4/6 (67%).</p><p><strong>Conclusions: </strong>Immunothrombosis offers a novel explanation for JAKi-associated VTE in RA.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145172655","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}

{"title":"Use of statins and its association with major adverse cardiovascular events with tofacitinib vs TNF inhibitors in patients with rheumatoid arthritis with and without atherosclerotic cardiovascular disease.","authors":"Jon T Giles, Christina Charles-Schoeman, Maya H Buch, Maxime Dougados, Zoltán Szekanecz, Ted R Mikuls, Steven R Ytterberg, Gary G Koch, Kenneth Kwok, Mary Jane Cadatal, Sujatha Menon, Yan Chen, Annette M Diehl, Jose L Rivas, Arne Yndestad, Deepak L Bhatt","doi":"10.1016/j.ard.2025.08.028","DOIUrl":"https://doi.org/10.1016/j.ard.2025.08.028","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to assess statin usage and its association with incident major adverse cardiovascular (CV) events (MACE) in patients with rheumatoid arthritis (RA) treated with tofacitinib vs tumour necrosis factor inhibitors (TNFi) in ORAL Surveillance.</p><p><strong>Methods: </strong>Patients with RA aged ≥50 years and ≥1 additional CV risk factor received tofacitinib 5 mg (N = 1455) or 10 mg twice a day (N = 1456) or TNFi (N = 1451). Statin treatment was assessed at baseline and during the study. Hazard ratios (HR) were evaluated for MACE in participants with a history of atherosclerotic cardiovascular disease (ASCVD) and in categories of predicted CV risk.</p><p><strong>Results: </strong>Among participants with a history of ASCVD or high CV risk, 53.0% and 26.9%, respectively, used a statin at baseline. Baseline statin use was similar in tofacitinib and TNFi-treated participants. In participants with or without statins, low-density lipoprotein and high-density lipoprotein increased from baseline and to a larger extent with tofacitinib than with TNFi. Occurrence of MACE in participants with a history of ASCVD and no use of statins at any time was higher with tofacitinib vs TNFi (HR 4.07 [95% CI 1.20-13.82]). In participants with a history of ASCVD and use of statins at baseline or at any time, there was no difference in incident MACE with tofacitinib vs TNFi (HR 1.17 [95% CI 0.46-3.00]).</p><p><strong>Conclusions: </strong>This post hoc analysis of ORAL Surveillance emphasises the gap in the CV preventive care of patients with RA. Among patients with a history of ASCVD, use of statins may mitigate the previously reported MACE risk observed to accompany tofacitinib use vs TNFi. This trial was registered with NCT number NCT02092467.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136186","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}