Annals of the Rheumatic Diseases最新文献

{"title":"Risk of first and second primary keratinocyte cancers in relation to treatment of rheumatoid arthritis with JAKi, TNFi, and non-TNFi bDMARDs-a Swedish nationwide study.","authors":"Viking Huss, Hannah Bower, Martin Björklund, Karin Hellgren, Thomas Frisell, Benedicte Delcoigne, Daniela Di Giuseppe, Johan Askling","doi":"10.1016/j.ard.2026.02.015","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.015","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to assess the risks of primary and second primary keratinocyte cancers (KCs) in patients with rheumatoid arthritis (RA) and in relation to treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic disease-modifying antirheumatic drugs.</p><p><strong>Methods: </strong>Nationwide cohort study of patients treated with Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitor (TNFi), or non-TNFi bDMARDs, using data from the Swedish Rheumatology Quality Register linked to other registers including the National Cancer Register, 2012 through 2023. Adjusted hazard ratios (HRs) were estimated via Cox regression using TNFi as reference.</p><p><strong>Results: </strong>We identified 21,756 unique patients with RA. Based on 155 incident KC with JAKi, 458 with non-TNFi and 766 with TNFi, the HR for JAKi vs TNFi was 1.39 (1.16-1.68), corresponding to 1 extra KC case per every 244 patients per year. For non-TNFi vs TNFi, the HR was 0.96 (0.86-1.08). By subtype, the HR for JAKi vs TNFi was 1.41 (1.13-1.75) for basal cell carcinoma and 1.49 (1.09-2.05) for squamous cell carcinoma (SCC). For abatacept vs etanercept, the HR for SCC was 1.48 (1.11-1.97). The HR for a second primary KC was 1.31 (0.94-1.82) for JAKi and 0.94 (0.75-1.17) for non-TNFi bDMARD vs TNFi.</p><p><strong>Conclusions: </strong>Patients treated with JAKi have an elevated risk of KC compared with patients treated with TNFi. Although the class of non-TNFi bDMARDs is not associated with increased KC risk, we repeated a drug-specific signal of increased risk for SCC with abatacept.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455292","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":"An app-based nonpharmacological intervention improves patient-reported disease activity, functionality, and quality of life in patients with axial spondyloarthritis: a randomised controlled trial.","authors":"Patrick-Pascal Strunz, Matthias Froehlich, Tobias Heusinger, Maxime le Maire, Anna Fleischer, Karsten Sebastian Luetkens, Patricia Possler, Michael Gernert, Hannah Labinsky, Ottar Gadeholt, Robert Leppich, Astrid Schmieder, Ludwig Hammel, Billy Sperlich, Hermann Einsele, Marc Schmalzing","doi":"10.1016/j.ard.2026.02.016","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.016","url":null,"abstract":"<p><strong>Objectives: </strong>No app-based nonpharmacological intervention has yet demonstrated to meaningfully improve disease activity, functional status, and disease-specific quality of life in axial spondyloarthritis (axSpA). We evaluated Axia, a CE-marked smartphone application designed for axSpA, that combines personalised exercise therapy, patient education, and disease management, supported by gamification for long-term adherence.</p><p><strong>Methods: </strong>To evaluate its clinical efficacy, a 12-week monocentric randomised controlled interventional trial was conducted involving 200 patients with axSpA with stable pharmacotherapy. Patients were randomised (1:1) to either using Axia (intervention group [IG]) or standard of care (control group [CG]).</p><p><strong>Results: </strong>A total of 186 participants (mean age 50.61 years, 66% females, 56% with radiographic axSpA, mean Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] 5.17, and 58% received biologicals or Janus kinase inhibitors) completed the study (95 in the IG and 91 in the CG). Compared to CG, participants in the IG demonstrated significant improvements in BASDAI (analysis of covariance [ANCOVA]-estimated group difference: -1.508, P < .001), Bath Ankylosing Spondylitis Functional Index (-1.139; P < .001), and Ankylosing Spondylitis Quality of Life questionnaire (-2.297; P < .001), all exceeding minimal clinically important difference thresholds. A significantly higher proportion of patients in the IG achieved an Assessment of Spondyloarthritis International Society (ASAS)20 response compared to the CG (51% vs 9%; P < .001), and the ASAS40 response rate was also higher (23% vs 3%; P < .001). No concerning safety signals were observed.</p><p><strong>Conclusions: </strong>These findings support the potential of Axia as a safe and effective nonpharmacological intervention to further improve the state of care of patients with axSpA in addition to conventional anti-inflammatory pharmacotherapy.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455313","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":"A novel murine model of early calcium pyrophosphate deposition disease based on the TNFRSF11B mutation mimics features of the human disease.","authors":"Chun Wang, Claudia M Gohr, Elizabeth Mitton-Fitzgerald, Arin K Oestreich, Yongjia Li, Jianqiu Xiao, Khushpreet Kaur, Farshid Guilak, Deborah J Veis, Ann K Rosenthal, Gabriel Mbalaviele","doi":"10.1016/j.ard.2026.02.014","DOIUrl":"10.1016/j.ard.2026.02.014","url":null,"abstract":"<p><strong>Objectives: </strong>Calcium pyrophosphate deposition (CPPD) disease is a common form of arthritis affecting older individuals. This disease is characterised by high levels of pyrophosphate in articular cartilage, resulting in calcium pyrophosphate crystal formation in humans and inflammatory and degenerative arthritis. A loss-of-function mutation in the TNFRSF11B locus (also known as CCAL1), which encodes osteoprotegerin (OPG) causes familial CPPD. OPG acts as a decoy receptor for RANKL, thereby inhibiting osteoclast differentiation and activity. CPPD currently lacks any animal models. The goal of this study was to develop a murine model of early CPPD by incorporating the TNFRSF11B gene mutation in mice and determining its effects on bones, joints and CPPD biomarkers.</p><p><strong>Methods: </strong>We used CRISPR/Cas9 editing to generate mice carrying the TNFRSF11B mutation (Opg^mt). Joint and bone phenotypes, bone remodelling biomarkers and key CPPD biomarkers were assessed in wild type (WT; Opg^wt/wt), Opg^wt/mt and Opg^mt/mt mice at 6 and 12 months of age.</p><p><strong>Results: </strong>Male and female mice carrying Opg^mt displayed osteopenia and high bone remodelling markers at 6 and 12 months of age. This phenotype was concurrent with increased osteoclast numbers and activity. Female Opg^mt/mt mice also displayed significant osteoarthritis features by 12 months of age, including articular cartilage loss in the lateral compartment of the knee based on Mankin structural damage scores. Additionally, biomarkers pathognomonic of CPPD disease, such as pyrophosphate, transforming growth factor (TGF)-β1 levels and ENPP1 activity, were significantly elevated in the joints of both 6- and 12-month-old female mice with OPG^mt.</p><p><strong>Conclusions: </strong>Mice carrying Opg^mt display bone and joint phenotypes characteristic of early-stage CPPD disease in humans. Opg^mt mice represent a novel preclinical model of early CPPD, ideal for exploring potential therapies targeting the disease prior to the development of major joint damage.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455329","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 the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update.","authors":"Josef S Smolen, Christopher J Edwards, Victoria Konzett, Faidra Laskou, Daniel Aletaha, Roberto Caporali, Thomas Dörner, Kimme L Hyrich, Elsa Mateus, Janet E Pope, Jette Primdahl, Savia de Souza, Tanja Stamm, Tsutomu Takeuchi, Désirée van der Heijde, Patrick Verschueren, Kevin L Winthrop, Jose Maria Alvaro-Gracia, Johan Askling, Joan Bathon, Maya H Buch, Gerd R Burmester, Catalin Codreanu, Philip G Conaghan, Maurizio Cutolo, Bruno Fautrel, Joao Fonseca, Laure Gossec, Espen Haavardsholm, Merete Lund Hetland, Annamaria Iagnocco, Pierre-Antonie Juge, Zhanguo Li, Rikke Helene Moe, Peter Nash, Gyula Poór, Andrea Rubbert-Roth, Raquel Dos Santos Sobrin, Hendrik Schulze-Koops, Russka Shumnalieva, Ladislav Senolt, Lucia Silva-Fernandez, Anja Strangfeld, Peter Taylor, Carl Turesson, Elsa van Duuren, Maarten de Wit, Ricardo Xavier, Andreas Kerschbaumer, Robert B M Landewé","doi":"10.1016/j.ard.2026.01.023","DOIUrl":"https://doi.org/10.1016/j.ard.2026.01.023","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to provide an update of the European Alliance of Associations for Rheumatology (EULAR) rheumatoid arthritis (RA) management recommendations addressing the most recent insights.</p><p><strong>Methods: </strong>An International Task Force was formed with a wide expertise and solicited 2 systemic literature research activities on the safety and efficacy of disease-modifying antirheumatic drugs (DMARDs). New evidence was discussed, considering the update from 2022. A voting process was applied to each item. Levels of evidence and strengths of recommendation were assigned, and participants voted on the levels of agreement.</p><p><strong>Results: </strong>The task force agreed on 5 overarching principles and reduced the number of recommendations to 9 concerning use of conventional synthetic DMARDs (methotrexate [MTX], leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b)DMARDs (tumour necrosis factor inhibitors [adalimumab, certolizumab pegol, etanercept, golimumab, infliximab], abatacept, rituximab, tocilizumab, sarilumab, including biosimilars) and targeted synthetic [ts]DMARDs (namely the Janus kinase inhibitors [JAKi] tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target), and tapering following clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were considered. Initially, MTX ideally in combination with short-term GCs is recommended; upon insufficient response after 3 to 6 months, a bDMARD should be added; after careful consideration of risks, including MACEs, malignancies and/or thrombo-embolic events, JAKi may also be considered. If the first bDMARD (or JAKi) fails, any other bDMARD (from another or the same class) or JAKi (considering risks) is recommended. With sustained remission, DMARDs may be tapered, but caution is required as stopping often leads to a flare. Levels of evidence and levels of agreement were high for most recommendations.</p><p><strong>Conclusions: </strong>These updated EULAR recommendations provide consensus on RA management based on currently available evidence regarding efficacy, safety, and cost.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147455294","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":"Quantitative MRI tenosynovitis volume explains the association between tendon involvement and future development of clinical arthritis in anti-cyclic citrullinated peptide-positive at-risk individuals.","authors":"Kerem Abacar, Yuya Tabuchi, Andrea Di Matteo, Laurence Duquenne, Emma Rowbotham, Jacqueline Nam, Paul Emery, Dennis McGonagle, Kulveer Mankia","doi":"10.1016/j.ard.2025.10.020","DOIUrl":"https://doi.org/10.1016/j.ard.2025.10.020","url":null,"abstract":"<p><strong>Objectives: </strong>Tenosynovitis is a key imaging feature in the preclinical phase of rheumatoid arthritis. Prior studies suggest that presence of magnetic resonance imaging (MRI) tenosynovitis may better predict future clinical arthritis than MRI synovitis. We hypothesised that the volume of subclinical inflammation within tendon sheaths may explain this association in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals. This study sought to assess whether MRI-derived tenosynovitis (TSV) and joint synovitis (SV) volumes predict inflammatory arthritis (IA) in anti-CCP-positive individuals without clinical synovitis, beyond clinical/serological markers.</p><p><strong>Methods: </strong>We included 223 anti-CCP-positive individuals with musculoskeletal symptoms without clinical synovitis. All underwent baseline contrast-enhanced MRI of the hand and wrist. TSV and SV were quantified via manual segmentation and three-dimensional (3D) reconstruction (OsiriX-MD). IA progression was defined as ≥1 clinically swollen joint. Cox regression and receiver operating characteristic (ROC) analyses were performed.</p><p><strong>Results: </strong>Of 223 participants, 67 (30%) developed IA over a median 13.3-month follow-up. Inter-reader agreement for volumetric scoring was excellent (intraclass correlation coefficient > 0.90 across all regions). Baseline tenosynovitis (34.5%) was associated with progression (P < .001). TSV was higher in progressors than non-progressors (1607 vs 705 mm³, P = .003), remained predictive after adjusting for SV (P = .008), and outperformed SV in ROC analysis (area under curve (AUC) = 0.697 vs 0.582). In multivariable analysis, TSV (P < .001) and tender joint count (P = .014) independently predicted progression beyond clinical and serological markers. Higher total inflammation volume correlated with shorter time to progression (P = .008).</p><p><strong>Conclusions: </strong>MRI-derived TSV independently predicts IA and outperforms SV. Quantitative TSV assessment may enhance risk stratification and support preventive strategies in at-risk individuals.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429838","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":"Hand-dominant joint involvement pattern associates with favourable, and polyarthritis with unfavourable, treatment response to both csDMARDs and bDMARDs in early rheumatoid arthritis: a combined analysis of NORD-STAR and BeSt trials.","authors":"Yasuo Nagafuchi, Tjardo D Maarseveen, Kristina Lend, Anna Rudin, Bjorn Gudbjornsson, Dan Nordström, Espen A Haavardsholm, Gerdur Gröndal, Jon Lampa, Kim Hørslev Petersen, Marte Schrumpf Heiberg, Merete Hetland, Mike Nurmohamed, Mikkel Østergaard, Ronald van Vollenhoven, Till Uhlig, Tuulikki Sokka-Isler, Erik B van den Akker, Tom W J Huizinga, Sytske Anne Bergstra, Rachel Knevel","doi":"10.1016/j.ard.2026.02.005","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.005","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the association between joint involvement pattern (JIP) subgroups and treatment responses to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biological disease-modifying antirheumatic drugs (bDMARDs), and to compare the impact of JIP subgroups with other clinical parameters in treatment-naïve patients with early rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>An individual patient data meta-analysis was conducted using 2 randomised controlled trials, NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) and Behandel-Strategieën (BeSt), including 1250 treatment-naïve patients with early RA. JIP subgroup assignment was based on 4 previously identified subgroups defined by baseline clinical characteristics, primarily joint involvement in the 66/68 joint scheme. Treatment outcomes were measured using the longitudinal Clinical Disease Activity Index (CDAI) and other disease activity indices through week 48. Associations of the JIP subgroups and other clinical predictors were evaluated using a mixed-model analysis.</p><p><strong>Results: </strong>Patients with a hand-dominant JIP (JIP-Hand) showed significantly better CDAI scores after treatment (Beta for CDAI = -1.4 [95% CI, -2.3 to -0.55]; p = .0016), whereas those with a polyarthritis pattern (JIP-Poly) exhibited worse outcomes (Beta = 0.95 [95% CI, 0.064-1.8]; p = .035). Female sex was also associated with worse CDAI scores (Beta = 1.2 [95% CI, 0.40-2.0]; p = .0031), whereas anticitrullinated protein antibodies did not show a significant association (Beta = 0.19 [95% CI, -0.69 to 1.1]; p = .67). When compared across groups, csDMARDs and combined bDMARDs were similarly effective in the respective JIP subgroups (interaction p > .10).</p><p><strong>Conclusions: </strong>In early RA, csDMARD and bDMARD treatments resulted in the greatest improvement in disease activity in JIP-Hand and the least improvement in JIP-Poly.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375982","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":"Prevalence and impact of suspected fibromyalgia on disease outcomes and treatment in axial spondyloarthritis: 10-year follow-up data from the DESIR cohort.","authors":"Clementina López-Medina, Sylvie Chevret, Cédric Lukas, Anna Moltó, Maxime Dougados","doi":"10.1016/j.ard.2026.02.006","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.006","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the prevalence of suspected fibromyalgia using the Fibromyalgia Rapid Screening Tool (FiRST) and its impact on disease burden, disability, TNF inhibitor (TNFi) initiation, and treatment retention over 10 years in patients with axial spondyloarthritis (axSpA) from the DESIR cohort.</p><p><strong>Methods: </strong>The FiRST questionnaire was administered annually from year 7 to year 10. Missing FiRST data were imputed using longitudinal multiple imputation. Patients were classified as suspected fibromyalgia-positive at baseline if they were FiRST-positive (FiRST ≥5/6) at least twice after multiple imputation. Associations with disease outcomes over the 10-year period were assessed using mixed models for repeated measures, adjusted for TNFi use. TNFi initiation and retention over 10 years were compared using Kaplan-Meier analyses.</p><p><strong>Results: </strong>The estimated prevalence of suspected fibromyalgia was 21.7% (144/663; 95% CI: 18.6-25.1). At baseline, suspected fibromyalgia was associated with a lower prevalence of HLA-B27 positivity and radiographic sacroiliitis, but similar rates of magnetic resonance imaging sacroiliitis and elevated C-reactive protein. Over 10 years, suspected fibromyalgia was consistently associated with higher self-reported disease activity, poorer health-related quality of life, and greater disability. Permanent disability at 10 years occurred more frequently in patients with suspected fibromyalgia (26.4% vs 9.4%; P < .001). TNFi initiation was more frequent (64.4% vs 46.1%), but treatment persistence at 1 year was significantly lower (42.0% vs 64.2%) in this group.</p><p><strong>Conclusions: </strong>Suspected fibromyalgia is common and clinically relevant in axSpA. It is associated with higher disease burden, increased biologic use, and poorer treatment persistence.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372127","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":"Psoriatic dactylitis: the association with HLA genetic susceptibility markers.","authors":"Fadi Kharouf, Virginia Carrizo Abarza, Pankti Mehta, Shangyi Gao, Darshini Ganatra, Daniel Pereira, Richard J Cook, Denis Poddubnyy, Dafna D Gladman, Vinod Chandran","doi":"10.1016/j.ard.2026.02.011","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.011","url":null,"abstract":"<p><strong>Objectives: </strong>Human leukocyte antigen (HLA) alleles, particularly of HLA-B and HLA-C, are associated with the susceptibility to and the expression of psoriatic arthritis (PsA). We aimed to identify HLA alleles and haplotypes associated with dactylitis and the time to resolution of tender dactylitis.</p><p><strong>Methods: </strong>We retrieved longitudinal data on 1216 patients with PsA followed at an observational cohort. We screened HLA-B and -C alleles with >5% frequency in our sample for association with dactylitis by employing logistic regression fitted using generalised estimating equations. We also analysed common haplotypes. We then used Cox regression, adjusted for confounders, to explore the association between these alleles and haplotypes with the time to resolution of the first tender dactylitis episode.</p><p><strong>Results: </strong>Dactylitis was observed in 584 (48%) patients over a median follow-up of 12.0 years (IQR: 5.7-20.1). HLA-B*27 (odds ratio [OR] 1.94, 95% CI 1.49-2.53), HLA-C*02 (OR 1.63, 95% CI 1.17-2.25), and HLA-B*27/C*02 (OR 1.88, 95% CI 1.32-2.67) were associated with a higher risk of dactylitis, whereas HLA-B*15 was associated with a lower risk (OR 0.72, 95% CI 0.54-0.98). A weaker association was observed for HLA-C*12 (OR 1.25, 95% CI 0.97-1.62) and HLA-B*27/C*01 (OR 1.40, 95% CI 0.99-2.00). Notably, HLA-B*27 was associated with slower resolution of tender dactylitis (hazard ratio 0.74, 95% CI 0.57-0.96).</p><p><strong>Conclusions: </strong>HLA-B*27 and -C*02 and the HLA-B*27/C*02 haplotype are associated with PsA dactylitis. HLA-B*27 may also influence the resolution of tender dactylitis. These alleles are thus associated with PsA dactylitis susceptibility and severity; replication studies are required.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368774","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":"How long do people with rheumatic and musculoskeletal diseases stay healthy and in work across Europe? Analysis of data from SHARE and ELSA.","authors":"Ross Wilkie, Oluwasikemi Onamusi, Jessica Potts, Marty Lynch","doi":"10.1016/j.ard.2026.02.010","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.010","url":null,"abstract":"<p><strong>Objectives: </strong>This study aims to estimate the extent of the reduction in healthy working life expectancy (HWLE), from age 50, for people with rheumatic and musculoskeletal diseases (RMDs) in 19 countries across Europe and highlight the need to target extending working lives through interventions and policy.</p><p><strong>Methods: </strong>Data were from 2 longitudinal studies (Survey of Health, Ageing and Retirement in Europe [2004-2022], English Longitudinal Study of Ageing [2002-2023]) that collect information in people aged 50 years and over. 'Healthy' and 'working' were defined as no limiting long-standing illness and employment/self-employment, respectively. RMDs were identified from self-report of ever having received a doctor diagnosis of arthritis or rheumatism. Age-adjusted discrete time 3-state models were fitted using IMaCh software, a maximum likelihood modelling programme using interpolation of Markov Chains, to estimate HWLE from transition probabilities between each healthy and working state based on RMD status (overall, by sex, education, and physical activity), stratified by 19 countries.</p><p><strong>Results: </strong>In 6 countries, HWLE in the population with RMDs was around 50% or less than for the population without RMDs. The lowest HWLE for populations with RMDs was in Austria 2.60 (1.49, 3.71) years which was 42.9% of HWLE for the population without RMDs. HWLE was lower in populations with RMDs with lower than upper secondary education in all countries and in populations with RMDs categorised as physically inactive in 16 countries.</p><p><strong>Conclusions: </strong>The differences observed in HWLE demonstrate the substantial societal burden associated with RMDs. However, differences by country, sex, education and physical activity indicate that there are opportunities for interventions and policies to increase HWLE.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368789","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":"Progression from at-risk state to clinical and severe systemic lupus erythematosus involves molecular dysregulations potentially reversible by biologics: implications for early diagnosis and treatment.","authors":"Sofia Papanikolaou, Evgenia Emmanouilidou, Christina Adamichou, Eleni Kalogiannaki, Dionysios Nikolopoulos, Micaela Fredi, Lucy Marie Carter, Chiara Tani, Noemin Kapsala, Argiro Repa, Nikos Malissovas, Panagiotis Garantziotis, Nestor Avgoustidis, Dimitra Nikoleri, Aggelos Banos, Giannis Vatsellas, Prodromos Sidiropoulos, Dimitrios Konstantopoulos, Dimitrios Boumpas, Edward M Vital, Laura Andreoli, Marta Mosca, Luís Inês, Christoforos Nikolaou, George Bertsias","doi":"10.1016/j.ard.2026.02.003","DOIUrl":"https://doi.org/10.1016/j.ard.2026.02.003","url":null,"abstract":"<p><strong>Objectives: </strong>Understanding the molecular events underlying systemic lupus erythematosus (SLE) onset and progression can facilitate early intervention strategies. We explored transcriptomic changes during progression from preclinical to clinical and advanced SLE, and assessed their potential reversibility by targeted agents.</p><p><strong>Methods: </strong>This includes multicentre prospective study of individuals with nondiagnostic features suggestive of SLE. Baseline blood RNA-sequencing was performed in groups who progressed to classifiable SLE or not (n = 36 each), and compared with healthy (n = 42) and early SLE (n = 43). Transcriptome analysis included supervised methods, gene module-based clustering, and drug reversibility/repurposing pipelines with publicly available data. An independent at-risk cohort (n = 15 progressors, n = 20 nonprogressors) was used to validate molecular classifiers.</p><p><strong>Results: </strong>At-risk individuals exhibited deregulated metabolic, cytokine signalling, haematologic, and stress-response pathways. Progressors vs nonprogressors showed heightened interferon (IFN)-alpha (α)/gamma (γ) and inflammatory cytokine activity, corroborated by Gene Set Enrichment Analysis and coexpression analysis, and intensified during SLE classification. Unsupervised modelling of gene module-eigengene patterns revealed molecular heterogeneity among progressors, differing in p53/insulin activity and Toll-like receptor (TLR) signalling. Importantly, we characterised a 17-gene susceptibility signature that predicted transition with an area under the curve 0.80 of the receiver operating characteris (95% CI: 0.65-0.94) in the external cohort. Analysis across the continuum-from healthy and at-risk states to early SLE and lupus nephritis-revealed stepwise upregulation of IFN-α/γ, haem metabolism, and oxidative phosphorylation pathways, with additional IFN-related genes activated in established disease. SLE susceptibility and progression signatures demonstrated in silico reversibility by anifrolumab and belimumab.</p><p><strong>Conclusions: </strong>IFN-α/γ and inflammatory cytokine signatures characterise evolving/early SLE, whereas amplification of IFN signalling and oxidative phosphorylation denotes severity. Blood molecular profiling may aid risk stratification and rationalise early biologic approaches.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.6,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147368782","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}