Clinical and experimental rheumatology最新文献

{"title":"Correction to: IL-1 targeting agents in Schnitzler syndrome: a multicentre, real-world study from the international AIDA Network Schnitzler Registry.","authors":"Laura Calabrese, Alessandra Cartocci, Antonio Vitale, Eduardo Martín-Nares, Martina D'Onghia, Valeria Caggiano, Jiram Torres-Ruiz, Roberta Lopez, Karina Jahnz-Rozyk, Katarzyna Rybak, Micol Frassi, Franco Franceschini, Francesca Crisafulli, Abdurrahman Tufan, Hamit Kucuk, Aslihan Avanoglu Guler, Antonio Gidaro, Leyla La Cava, Francesca Della Casa, Ilaria Mormile, Elisa Cinotti, Giuseppe Lopalco, Jurgen Sota, Jessica Sbalchiero, Giacomo Emmi, Andreas Recke, Stefania Costi, Paolo Sfriso, Sara Monti, Ombretta Viapiana, Andrea Hinojosa-Azaola, Alberto Balistreri, Claudia Fabiani, Bruno Frediani, Pietro Rubegni, Ewa Wiesik-Szewczyk, Luca Cantarini","doi":"10.55563/clinexprheumatol/ys6qle","DOIUrl":"https://doi.org/10.55563/clinexprheumatol/ys6qle","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":"44 5","pages":"1056"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High sensitivity measurement of circulating interferon proteins in systemic lupus erythematosus.","authors":"Yun-Ju Huang, Charlotte M Bottomley, Robert T Maughan, Alex Field, Geoffrey H D Leung, Liz Lightstone, Thomas D Cairns, Tabitha Turner-Stokes, Marie B Condon, James E Peters, Marina Botto, Matthew C Pickering","doi":"10.55563/clinexprheumatol/lyd5es","DOIUrl":"10.55563/clinexprheumatol/lyd5es","url":null,"abstract":"<p><strong>Objectives: </strong>Increased expression of type I interferon-induced genes is a hallmark of systemic lupus erythematosus (SLE). Measurement of interferon proteins in plasma has been challenging due to their low abundance. Here we utilise a new high sensitivity assay to evaluate levels of interferon proteins in SLE patients.</p><p><strong>Methods: </strong>Seven interferon proteins (type I: IFNα1:IFNα13, IFNα2, IFNβ, IFNω; type II: IFNγ; type III: IFNλ1, IFNλ2:IFNλ3) were measured in 266 SLE patients using the NULISAseq Inflammation Panel 250 (Alamar Biosciences). IFN profiles (normal or high) were determined using the 95th percentile threshold in healthy controls for each IFN protein. Their relationship to disease activity and type I interferon-stimulated gene (ISG) scores was assessed.</p><p><strong>Results: </strong>All seven IFN proteins were significantly increased in SLE patients compared to healthy controls and were higher in patients with anti-Sm, anti-Ro and anti-RNP antibodies. IFNα1:IFNα13, IFNα2 and IFNω strongly correlated with the ISG score whereas IFNβ did not. The median levels of IFNα1:IFNα13, IFNα2, IFNω, IFNλ1 and IFNλ2:IFNλ3 progressively increased with disease activity whereas this was not the case for either IFNβ or IFNγ. The most frequent IFN profiles were high type I+III (35%, n=93); normal levels of all IFN proteins (25%, n=67); high type I only (21%, n=56); and high type I+II+III (13%, n=34). The latter associated with serological activity (low complement and high dsDNA antibody titres) and nephritis.</p><p><strong>Conclusions: </strong>Plasma levels of type I IFN proteins (IFNα1: IFNα13, IFNα2 and IFNω but not IFNβ) and type III IFN proteins (IFNλ1, IFNλ2:IFNλ3) were increased in active disease groups and ISG scores recapitulated this. Longitudinal intra-individual measures of these proteins are needed to explore their utility as biomarkers for SLE disease activity.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"925-937"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug-induced osteoporosis/osteopenia: a pharmacovigilance analysis using the FDA Adverse Event Reporting System database.","authors":"Yan Wang, Guanjun Huang, Xingxiang Fu, Zhiyong Wang, Wei Mao, Guihao Zheng","doi":"10.55563/clinexprheumatol/9vqg6f","DOIUrl":"10.55563/clinexprheumatol/9vqg6f","url":null,"abstract":"<p><strong>Objectives: </strong>Drug-induced osteoporosis/osteopenia (OP/OPN) has emerged as a significant public health concern affecting bone health. However, the risk assessment of OP/OPN induced by various drugs remains incompletely understood, necessitating large-scale real-world data analysis to clarify the associated risks. The present study aims to systematically analyse OP/OPN-related adverse events (AEs).</p><p><strong>Methods: </strong>This study utilised the FDA Adverse Event Reporting System (FAERS) database to identify OP/OPN-related adverse event reports from 2004 to 2023. Disproportionality analysis, including the reporting odds ratio and proportional reporting ratio, was applied to evaluate the signal strength of OP/OPN associated with different drug categories. Additionally, the study analysed drug classifications, time-to-onset, and trends over time.</p><p><strong>Results: </strong>Among the 43,685 OP/OPN-related reports, anti-retroviral drugs accounted for the highest proportion of reports (20.73%), with a gradual annual increase in reporting frequency (average annual growth rate of 2.20%). This was followed by immunomodulatory/immunosuppressive agents (12.76%), proton pump inhibitors (6.25%), and hormone-related (2.88%). A significant variation was observed in the time-to-onset of OP/OPN-related adverse event among different drug categories: glucocorticoids-induced osteoporosis occurred earliest (median time-to-onset of 164 days), while anti-retroviral drug-induced osteoporosis had the longest time-to-onset (median of 1,508 days). Regarding reporting frequency, tenofovir and its combinations, esomeprazole, adalimumab, methotrexate, medroxyprogesterone, interferon beta-1A, etanercept, and rituximab were the most frequently reported drugs. In terms of signal strength, tenofovir and its combinations, adefovir, pamidronic acid, and esomeprazole the strongest signals, suggesting that these drugs may represent key risk factors for OP/OPN.</p><p><strong>Conclusions: </strong>This FAERS-based study identified multiple drug classes associated with OP/OPN-related adverse event signals, with anti-viral drugs - particularly tenofovir disoproxil and its combination therapies - exhibiting the strongest signal. Although glucocorticoids had a lower reporting proportion, their short onset time underscores the need for vigilance. These findings provide real-world evidence for drug safety management and highlight the necessity of bone health monitoring in long-term medication users. Future studies should integrate clinical data to validate these findings and explore underlying mechanisms.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"985-995"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the comorbidity mechanism of rheumatoid arthritis and systemic lupus erythematosus through transcriptomics and conducting experimental validation.","authors":"Minghui Shen, Chongge You","doi":"10.55563/clinexprheumatol/1xlydo","DOIUrl":"10.55563/clinexprheumatol/1xlydo","url":null,"abstract":"<p><strong>Objectives: </strong>Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are two systemic autoimmune diseases with significant comorbidity, and the shared molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>This study integrates four transcriptomic datasets (GSE17755, GSE110169, GSE93272, GSE110174), combining differential expression gene (DEG) screening, protein-protein interaction (PPI) network analysis, machine learning (LASSO and random forest), and single-sample gene set enrichment analysis (ssGSEA) to systematically analyse the comorbidity mechanisms of RA and SLE.</p><p><strong>Results: </strong>It was found that RA and SLE share immune regulatory genes such as IFIT3, TNFSF13B, and ZCCHC2, which are significantly upregulated in both diseases and have high diagnostic efficacy. Functional analysis shows that IFIT3 is associated with type I interferon and cGAS-STING pathways, TNFSF13B (BAFF) is associated with B cell activation and TLR signalling pathways, and ZCCHC2 is associated with cell cycle regulation and neurodegenerative diseases. Immune cell analysis indicates that in RA, macrophages are positively correlated with TNFSF13B, while in SLE, plasmacytoid dendritic cells (pDCs) are negatively correlated with IFIT3, suggesting disease-specific differences in the immune microenvironment.</p><p><strong>Conclusions: </strong>This study elucidates the molecular mechanisms of RA and SLE comorbidity, identifies cross-disease biomarkers and their interactions with immune cells and drugs, providing theoretical basis for precision diagnosis and treatment. The study limitations include data heterogeneity and the lack of Rhupus patient samples, which need to be validated through functional experiments and multicentre cohorts in the future.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"957-970"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasensitive serum interleukin-8 levels show no association with disease activity or autoantibody profile but relate to cardiovascular comorbidity in systemic lupus erythematosus.","authors":"Miguel Ángel González-Gay, Fuensanta Gómez-Bernal, Elena Heras-Recuero, Juan Carlos Quevedo-Abeledo, Antonia De Vera-González, Beatriz Tejera-Segura, Cristina Gómez-Moreno, Enrique García-Barrera, Luisa María Villar, J Gonzalo Ocejo-Vinyals, Raquel Largo, Iván Ferraz-Amaro","doi":"10.55563/clinexprheumatol/jgz1oz","DOIUrl":"10.55563/clinexprheumatol/jgz1oz","url":null,"abstract":"<p><strong>Objectives: </strong>Interleukin 8 (IL-8) is a chemokine responsible for attracting neutrophils to inflammatory foci, facilitating their migration through interactions with adhesion molecules. Although cytokines play an important role in the pathogenesis of systemic erythematosus (SLE), the clinical relevance of circulating IL-8 levels remains uncertain due to technical difficulties in its measurement in serum. Consequently, information linking serum IL-8 concentrations with specific clinical features of SLE is limited. This study aimed to explore the relationship between serum IL-8 levels and disease activity, serological, and cardiovascular features in patients with SLE.</p><p><strong>Methods: </strong>In this observational and cross-sectional study, a total of 235 patients with SLE were enrolled and underwent comprehensive characterisation, including assessment of autoantibody profiles, disease activity indices (SLEDAI-2K, LLDAS), damage index (SLICC-DI), and remission status (DORIS). Cardiovascular characteristics were also assessed, including lipid profiles, insulin resistance indices, and carotid ultrasound parameters such as plaque presence, intima-media thickness, and arterial stiffness. Serum IL-8 concentrations were quantified using an innovative ultrasensitive technique, the Single Molecule Array (Simoa®). Multivariable linear regression analyses were conducted to examine the associations between circulating IL-8 levels and clinical as well as cardiovascular manifestations of SLE.</p><p><strong>Results: </strong>Disease activity scores, damage indices, and autoantibody profiles did not show significant associations with IL-8 levels. Regarding cardiovascular factors, IL-8 was inversely associated with total and non-HDL cholesterol levels in the adjusted models. The Systematic Coronary Risk Evaluation 2 (SCORE2) cardiovascular risk score showed a significant positive association with IL-8.</p><p><strong>Conclusions: </strong>In SLE, IL-8 is not associated with disease activity or autoantibody profile but may contribute mechanistically to dyslipidaemia and accelerated atherosclerosis.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"948-956"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parvovirus B19 infection with rheumatologic manifestations: results from a multicentre Italian study.","authors":"Federico Aldegheri, Riccardo Bixio, Alessandro Volpe, Alessandro Giollo, Marco Fornaro, Andrea Morciano, Martina Orlandi, Camilla Benini, Alessandro Biglia, Emanuele Bozzalla Cassione, Augusta Ortolan, Davide Bertelle, Giovanni Orsolini, Francesca Ruzzon, Mariangela Salvato, Antonio Carletto, Francesco Campanaro, Elisabetta Chessa, Elena Fracassi, Isotta Galvagni, Giovanni Adami","doi":"10.55563/clinexprheumatol/p64ofs","DOIUrl":"10.55563/clinexprheumatol/p64ofs","url":null,"abstract":"<p><strong>Objectives: </strong>To characterise the clinical spectrum of adult parvovirus B19 (B19V) infection referred for rheumatologic evaluation and to identify clinical predictors of arthritis resolution.</p><p><strong>Methods: </strong>We conducted a multicentre retrospective study across nine Italian rheumatology units during the 2023-2024 post-pandemic resurgence of B19V infection. Clinical, therapeutic, and follow-up data were systematically collected using a standardised REDCap platform.</p><p><strong>Results: </strong>We enrolled 71 patients (median age 43 years; 72% female), 85% with a confirmed diagnosis. Most reported recent household exposure. Joint involvement was nearly universal (96%), predominantly oligoarticular, and often affected large joints, mimicking early inflammatory arthritis. Fever (65%) and skin manifestations (61%) were frequent. In addition to typical exanthems, 9 patients displayed a distinctive purpuric rash confined to the pretibial region, sparing ankles and feet - a potentially distinctive feature of to B19V infection. Symptom resolution occurred in 87% of cases, usually within one month. Glucocorticoid use was independently associated with - but not proven to cause - faster resolution in Cox regression (HR 0.53; 95% CI: 0.31-0.90; p=0.020), though this finding may reflect indication bias. No other clinical or serological predictors emerged.</p><p><strong>Conclusions: </strong>This study provides the largest systematically collected multicentre cohort of adults with B19V infection referred to rheumatology during the post-pandemic European outbreak. Our findings expand the clinical spectrum of B19V arthritis and highlight distinctive skin patterns that may aid differential diagnosis during epidemic waves.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"895-902"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146009251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of neutrophils in connective tissue disease-associated interstitial lung disease.","authors":"Haolong Wang, Yilin Lu, Jing Liu, Zhihan Sang, Wenqiang Fan, Yanli Liu, Juntang Lin","doi":"10.55563/clinexprheumatol/su8rvb","DOIUrl":"10.55563/clinexprheumatol/su8rvb","url":null,"abstract":"<p><p>Connective tissue disease-associated interstitial lung disease (CTD-ILD) is a subtype of ILD that arises due to autoimmune disorders. Unlike other ILDs, CTD-ILD is strongly linked to genetic predisposition, environmental factors, and dysfunction of the immune system. The primary pathogenesis involves immune cells erroneously attacking lung tissues in the context of autoimmune diseases; however, the precise pathogenic mechanisms remain elusive. As core driving factor of autoimmune diseases, immune cells play a pivotal role in the development of CTD-ILD. Neutrophils, key components of the innate immune system, are responsible for defending against infections and are critical in orchestrating immune responses. Notably, neutrophils can combat infections through phagocytosis or by releasing neutrophil extracellular traps (NETs).Recent studies have revealed significant dynamic changes in the quantity and function of neutrophils during the progression of CTD-ILD, highlighting their crucial role in this process. This review not only summarises the clinical manifestations of ILD associated with autoimmune diseases but also investigates the role of neutrophils in autoimmune diseases and inflammation, offering insights into the development of novel therapeutic strategies targeting abnormal neutrophil activity in CTD-ILD.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1036-1045"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resolution of refractory systemic lupus erythematosus-associated alopecia with anifrolumab: a case report.","authors":"Giorgio Buscetta, Chiara Rizzo, Giuliana Guggino","doi":"10.55563/clinexprheumatol/udjhxr","DOIUrl":"10.55563/clinexprheumatol/udjhxr","url":null,"abstract":"","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"1052"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MXRA5 is identified and validated as a key gene related to epithelial-mesenchymal transition in rheumatoid arthritis fibroblast-like synoviocytes.","authors":"Haiguang Lv, Yanju Li, Ruiqiang Wang, Yang Gao","doi":"10.55563/clinexprheumatol/dt5mf6","DOIUrl":"10.55563/clinexprheumatol/dt5mf6","url":null,"abstract":"<p><strong>Objectives: </strong>The invasion of fibroblasts is a major cause of cartilage destruction in rheumatoid arthritis (RA). The epithelial-to-mesenchymal transition (EMT) is a key factor that enhances the proliferation, invasion and migration abilities of cells. This study aims to identify important EMT-related genes in the synovial cells of RA using single-cell analysis and various machine learning methods, followed by functional validation.</p><p><strong>Methods: </strong>The RA-related single-cell dataset SDY 998 was employed to investigate the heterogeneity of EMT across different cell types using the AUCcell and AddModuleScore algorithms. By intersecting the high EMT-related genes with the differentially expressed genes (DEGs), we obtained the EMT-related DEGs for subsequent correlation analysis. We then used five machine learning algorithms: Xtreme Gradient Boosting (XGBoost), Boruta, Random Forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine Recursive Feature Elimination (SVM-RFE) to identify the optimal feature genes in the bulk RNA datasets. To validate the accuracy of our analysis, we conducted functional experiments on MH7A cells.</p><p><strong>Results: </strong>After analysing the scRNA-seq dataset with various algorithms, we found that fibroblast cells exhibited significantly high EMT activity. Fifty genes were identified as high EMT-related DEGs for subsequent analysis. The five machine learning algorithms revealed that MXRA5 and LRRC15 were significantly upregulated in RA fibroblast cells. Functional experiments confirmed that knockdown of MXRA5 significantly reduced the proliferation, migration, and invasion capabilities of the cells.</p><p><strong>Conclusions: </strong>MXRA5 was identified as a key gene related to EMT in fibroblast-like synoviocytes of RA patients. Knockdown of MXRA5 could suppress the proliferation, migration, and invasion capabilities of MH7A cells.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"938-947"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment sequences and lines of therapy in rheumatoid arthritis: a real-world evaluation of retention and effectiveness.","authors":"Mohammad Movahedi, Bindee Kuriya, Angela Cesta, Xiuying Li, Sibel Zehra Aydin, Claire Bombardier, Pooneh Akhavan","doi":"10.55563/clinexprheumatol/y1vbr1","DOIUrl":"10.55563/clinexprheumatol/y1vbr1","url":null,"abstract":"<p><strong>Objectives: </strong>Many patients with rheumatoid arthritis (RA) do not maintain disease control or tolerance their first advanced therapy (AT), making subsequent treatment choices critical. This study described real-world patterns of sequential AT use and evaluate drug survival and effectiveness across multiple lines of therapy in a large Canadian RA cohort.</p><p><strong>Methosd: </strong>Adult RA patients from the Ontario Best Practice Research Initiative (OBRI) who initiated AT between 2008 and 2023 were included. Drug survival was defined as time from initiation to discontinuation. Effectiveness was assessed using changes in Clinical Disease Activity Index (CDAI), achievement of minimal clinically important difference (MCID), low disease activity (LDA), and remission at 6 months. Outcomes were compared before and after 2010, the year treat-to-target (T2T) guidelines were introduced. Analyses were adjusted using propensity scores and multiple imputation for missing data.</p><p><strong>Results: </strong>Among 2,449 patients, TNFi agents were the most common first-line AT. Drug survival decreased with each subsequent line. Patients initiating AT after 2010 had shorter treatment durations (median 7.63 vs. 12.2 years), reflecting more frequent switching under T2T strategies. First-line therapies showed greater CDAI improvement and higher MCID, LDA, and remission rates. Effectiveness declined in later lines but remained clinically meaningful.</p><p><strong>Conclusions: </strong>This study offers insights into real-world sequential AT use in Canadian RA care. First-line AT is associated with superior survival and effectiveness; however, subsequent therapies continue to provide important clinical benefits. These findings support the value of personalised sequential treatment strategies and highlight the need for further research to inform future RA management guidelines.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":"978-984"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145502528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}