RMD Open最新文献

{"title":"Clinical and immunological outcomes of rituximab-based, mycophenolate mofetil-based and cyclophosphamide-based treatment strategies for systemic lupus erythematosus with active kidney involvement from LOOPS registry.","authors":"Masanobu Ueno, Ippei Miyagawa, Hiroaki Tanaka, Satoshi Kubo, Yusuke Miyazaki, Yasuyuki Todoroki, Yuya Fujita, Ryuichiro Kanda, Hidenori Sakai, Katsuhide Kusaka, Shingo Nakayamada, Yoshiya Tanaka","doi":"10.1136/rmdopen-2026-007370","DOIUrl":"10.1136/rmdopen-2026-007370","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the clinical outcomes and explore longitudinal peripheral blood immunophenotypic changes associated with rituximab (RTX)-based, mycophenolate mofetil (MMF)-based or intravenous cyclophosphamide (IVCY)-based treatment strategies for patients with systemic lupus erythematosus (SLE) and active lupus nephritis.</p><p><strong>Methods: </strong>We retrospectively analysed patients with SLE and active lupus nephritis enrolled in the LOOPS registry who received single-agent induction therapy with RTX, MMF or IVCY in addition to glucocorticoids (GCs). The co-primary endpoints were the achievement rates of complete renal response (CRR) and urinary protein-to-creatinine ratio <0.7 g/gCr at week 52. Secondary endpoints included renal function, proteinuria, disease activity, relapse rate and safety. Peripheral blood immune cell subsets were assessed by multicolour flow cytometry before and after treatment.</p><p><strong>Results: </strong>At week 52, no significant differences were observed in CRR rates or improvement in proteinuria among the groups. Changes in estimated glomerular filtration rate, disease activity measures and concomitant GC dose also did not differ significantly. Exploratory within-strategy analyses showed reduced B-cell subset proportions with RTX and broader reductions, including in activated T cells, with MMF and IVCY. However, treatment strategy-by-time interaction was not significant, providing no evidence of between-strategy differences in longitudinal changes.</p><p><strong>Conclusion: </strong>The 52-week clinical effectiveness of the RTX-based, MMF-based and IVCY-based strategies for active lupus nephritis did not differ significantly. Different within-strategy immunophenotypic patterns were observed, but between-strategy differences were not confirmed. Comprehensive immunophenotyping may help characterise immune dynamics and support future response stratification and precision medicine for lupus nephritis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064346","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":"Predicting disease flares in axial spondyloarthritis using different machine learning models in the METEOR-SpA registry.","authors":"Benavent D, Fanjul V, Bergstra S A, van Gaalen F, Arends S, Spoorenberg A, Dougados M, Kılıç L, Poddubnyy D, López-Medina C, Parperis K, Vega-Morales D, van der Heijde D, Navarro-Compán V","doi":"10.1136/rmdopen-2026-007147","DOIUrl":"10.1136/rmdopen-2026-007147","url":null,"abstract":"<p><strong>Objectives: </strong>To develop and externally validate machine learning models for predicting disease flares in axial spondyloarthritis (axSpA) using real-world registry data.</p><p><strong>Methods: </strong>Patients with axSpA receiving biological disease-modifying antirheumatic drugs in the METEOR-SpA registry were analysed at visit level. Flare was defined as an Axial Spondyloarthritis Disease Activity Score (ASDAS) increase ≥0.9 (or Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) increase ≥2) at the next 6-month assessment. Candidate models utilising routine clinical predictors and minimum-redundancy maximum-relevance variable selection were optimised for average precision (AP) to account for class imbalance, evaluated using patient-grouped cross-validation (CV) and externally validated in the Groningen Leeuwarden AxSpA cohort (GLAS) using discrimination, calibration and decision curve analysis (DCA).</p><p><strong>Results: </strong>After eligibility criteria, 1167 patients and 3865 visits were included from the METEOR-SpA cohort; 618 (52.9%) patients had at least one visit with known flare status. Among them, 170 (27.5%) experienced at least one flare. A ridge logistic regression was selected as the final model with an internal CV receiver operating characteristic plot and area under the curve (ROC-AUC) of 0.72 (95% CI 0.70 to 0.75) and an AP of 0.291 (0.245 to 0.337), retaining eight predictors associated with flare. These were ASDAS (current and previous), female sex, flare history, enthesitis, infliximab exposure, physician global assessment and C reactive protein. In external validation in GLAS, ROC-AUC was 0.63 (95% CI 0.59 to 0.68) and AP 0.142 (0.116 to 0.171). DCA showed a modest positive net clinical benefit at low threshold probabilities.</p><p><strong>Conclusions: </strong>A reduced logistic-regression model showed moderate internal and modest external discrimination for short-term flare risk in axSpA. While not intended to guide individual pre-emptive therapy modification, the model may support low-risk interventions such as group-level risk stratification or tighter follow-up after further validation.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040460","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":"Risk of cognitive disorders in patients with primary Sjögren's disease: data from Korean Health Insurance Service.","authors":"Hong Ki Min, Seung Won Lee, Sunyeup Kim, Gahyun Kim, Su-Jin Moon","doi":"10.1136/rmdopen-2026-006864","DOIUrl":"10.1136/rmdopen-2026-006864","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the risk of incident cognitive disorders in patients with primary Sjögren's disease (pSjD) using nationwide Korean National Health Insurance Service data.</p><p><strong>Methods: </strong>This retrospective cohort study included patients newly diagnosed with pSjD between 2010 and 2021 and propensity score-matched controls. The primary outcome was a composite of Alzheimer's dementia (AD), vascular dementia (VaD), secondary dementia, unclassified dementia and mild cognitive impairment (MCI). Adjusted HRs (aHRs) and 95% CIs were estimated using multivariable Cox regression. Age-stratified analyses were also performed.</p><p><strong>Results: </strong>A total of 12 731 patients with pSjD and 36 514 matched controls were analysed. pSjD was associated with increased risks of total cognitive disorders (aHR 1.48, 95% CI 1.36 to 1.63), AD (aHR 1.48, 95% CI 1.35 to 1.63), secondary dementia (aHR 2.24, 95% CI 1.45 to 3.48), unclassified dementia (aHR 1.43, 95% CI 1.21 to 1.70) and MCI (aHR 1.62, 95% CI 1.41 to 1.85). In age-stratified analyses, pSjD was associated with an increased risk of MCI among participants aged <65 years (aHR 1.46, 95% CI 1.06 to 2.01). Among those aged 65-74 years, pSjD was associated with increased risks of total cognitive disorders, AD and MCI.</p><p><strong>Conclusions: </strong>pSjD was associated with increased risks of multiple cognitive disorders. The age-specific patterns-an increased risk of MCI among individuals aged <65 years and increased risks of total cognitive disorders, AD and MCI among those aged 65-74 years-underscore the need for clinical attention to cognitive symptoms across age groups in patients with pSjD.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040501","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 initial treatment strategy and progression to difficult-to-treat rheumatoid arthritis (D2T-RA): evidence from a 20-year-old real-world cohort.","authors":"Cécile Van Mullem, Francesco Natalucci, Alexandra Avramovska, Tatiana Sokolova, Clément Triaille, Patrick Durez","doi":"10.1136/rmdopen-2026-007098","DOIUrl":"10.1136/rmdopen-2026-007098","url":null,"abstract":"<p><strong>Background/objectives: </strong>Despite major advances in rheumatoid arthritis (RA) management, a substantial proportion of patients evolve to difficult-to-treat RA (D2T-RA). We estimated the probability of progression to D2T-RA and assessed whether the initial choice of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) is associated with this risk.</p><p><strong>Methods: </strong>We retrospectively analysed 675 patients with established RA from the first consultation through all b/tsDMARD lines to the last follow-up or D2T-RA classification. Kaplan-Meier, log-rank and multivariable Cox regression analyses were performed to identify factors associated with D2T-RA progression.</p><p><strong>Results: </strong>Of the 675 patients (mean follow-up of 217.1±131.16 months), 126 (18.7%) fulfilled the D2T-RA criteria. Tumour necrosis factor inhibitor (TNFi) accounted for most first-line and second-line treatments (81.0% and 53.2%). In the post-2000 subcohort (498 patients), no significant difference in D2T-RA risk was observed between TNFi and non-TNFi starters nor between TNFi-cycling or other mechanism of action (MoA)-switching strategies. Glucocorticoid exposure was independently associated with increased risk (HR 2.47, 95% CI 1.38 to 4.42) and delayed b/tsDMARD initiation with decreased hazard (HR 0.990, 95% CI 0.98 to 0.996).</p><p><strong>Conclusion: </strong>In this observational cohort, initial MoA choice was not associated with D2T-RA progression. Disease severity markers appeared more prominent than treatment strategies in driving refractory evolution. Validation in a prospective/randomised setting is required before potential transition into clinical practice.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031380","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":"Integrated serum proteomics and autoantibody analyses reveal a biomarker signature predictive of flare during biologic tapering in rheumatoid arthritis.","authors":"Francisco J Blanco, Patricia Quaranta, Pablo Domínguez-Guerrero, Valentina Calamia, Patricia Fernández-Puente, Rocío Paz-González, Vanesa Balboa-Barreiro, Diana Noriega, Laura Galindo, Belén Acasuso, Natividad Oreiro, Ricardo Rojo, Lucía Lourido, Cristina Ruiz-Romero","doi":"10.1136/rmdopen-2026-007198","DOIUrl":"10.1136/rmdopen-2026-007198","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers predicting which patients with rheumatoid arthritis (RA) can safely undergo biologic tapering are currently lacking. This study aimed to identify circulating protein biomarkers predictive of flare during biologic disease-modifying anti-rheumatic drug tapering in RA.</p><p><strong>Methods: </strong>Baseline serum samples from patients with RA in sustained remission enrolled in the Biologic Optimisation (OPTIBIO) clinical trial were analysed using a two-stage design comprising an exploratory mass spectrometry in a discovery sample subset (n=44, 22 in the optimisation arm and 22 in the control arm), followed by ELISA validation of selected protein biomarkers and anti-cytokine autoantibody profiling in the full cohort (n=194). The primary outcome was a disease flare during follow-up.</p><p><strong>Results: </strong>During follow-up, disease flare occurred in 46.4% of patients in the optimisation arm and 30.9% in the control arm. Within the discovery subset of the optimisation arm, 87 proteins were differentially abundant between patients who flared and those who remained in remission. V-set immunoglobulin-domain-containing 4 (VSIG4) was validated as a biomarker associated with increased flare risk while anti-interferon-γ (anti-IFNγ) autoantibodies were also independently associated with flare. A combined model integrating VSIG4, anti-IFNγ and Disease Activity Score 28-joint count using C reactive protein improved discrimination compared with the clinical model alone (area under the curve (AUC) 0.760 vs 0.666) and showed higher sensitivity and greater potential clinical utility in decision curve analysis. In a secondary exploratory subgroup of patients with prolonged remission, predictive performance further improved (AUC 0.839).</p><p><strong>Conclusion: </strong>These findings identify a promising protein biomarker signature associated with flare during biologic tapering in RA, supporting biomarker-guided risk stratification in treatment optimisation strategies. External validation is required before clinical implementation.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031434","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":"Blinatumomab as the first-line induction for ANCA-associated rapidly progressive glomerulonephritis.","authors":"Juan Wang, Ye Yu, Rui Li, Bisheng Shi, Wenyi Wu, Huihua Ding, Fang Du, Shuang Ye, Sheng Chen","doi":"10.1136/rmdopen-2026-006790","DOIUrl":"10.1136/rmdopen-2026-006790","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13629879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031421","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":"Distinct molecular signature in relapsed patients with ANCA-associated vasculitis.","authors":"Chrysoula G Gialouri, Dimitrios Valakos, Savvina Moustafa, Christos Koutsianas, Aglaia Chalkia, Dimitrios Petras, Dimitrios T Boumpas, Aggelos Banos, Dimitrios Vassilopoulos","doi":"10.1136/rmdopen-2026-007063","DOIUrl":"10.1136/rmdopen-2026-007063","url":null,"abstract":"<p><strong>Objectives: </strong>The pathogenesis of relapses in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) remains ill defined. We aimed to identify whether there are any differences in the molecular profile between patients with relapsing versus new-onset disease.</p><p><strong>Methods: </strong>Whole blood RNA sequencing in 21 patients with MPA or GPA and 12 age-matched/sex-matched healthy controls was performed; 11 patients had active disease, either newly diagnosed (treatment-naïve, n=6) or relapsed (off-therapy, n=5) and 10 were in remission, either on (n=4) or off (n=6) maintenance therapy. Differential gene expression and functional enrichment analysis were conducted.</p><p><strong>Results: </strong>Relapsing patients with MPA/GPA exhibited a distinct molecular profile compared with healthy controls, newly diagnosed patients or those in remission. Specifically, patients with a major relapse displayed a unique pattern of 41 neutrophil degranulation-associated genes, encoding neutrophil granular proteins, proteins mediating neutrophil adhesion and chemotaxis and proteins involved in myelopoiesis.</p><p><strong>Conclusions: </strong>In this well-defined MPA/GPA cohort, we report for the first time a distinct relapse-associated transcriptional signature consistent with enhanced neutrophil activity. Therapies targeting neutrophil activation could represent a novel approach for preventing or treating relapses in MPA/GPA.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13636333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031377","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":"Evaluating a guideline-aligned prednisone threshold within the Lupus Low Disease Activity State (LLDAS): associations with damage accrual.","authors":"Ioannis Parodis, Rama Andraos, Matteo Bottai, Christopher Sjöwall","doi":"10.1136/rmdopen-2026-007162","DOIUrl":"10.1136/rmdopen-2026-007162","url":null,"abstract":"<p><strong>Objective: </strong>To examine whether a modified Lupus Low Disease Activity State with a prednisone-equivalent threshold ≤5 mg/day (LLDAS-5) is more strongly associated with lower damage accrual than conventional LLDAS using a ≤7.5 mg/day threshold (LLDAS-7.5) in systemic lupus erythematosus (SLE).</p><p><strong>Methods: </strong>We analysed 332 patients, including 105 incident cases. For each patient, yearly Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) worsening occasions and average proportion of follow-up spent in LLDAS-5 and LLDAS-7.5 were derived. Patient-level Poisson regression with follow-up years as the exposure and Huber's robust variance estimator estimated rate ratios (RRs). Parallel models were fitted for the two definitions. Full-cohort multivariable models adjusted for age, sex, ethnicity, SLE duration, baseline Systemic Lupus Erythematosus Disease Activity Index 2000 and baseline SDI.</p><p><strong>Results: </strong>In the full cohort, 142/332 patients experienced at least one SDI increase (190 occasions). Crude RRs were 0.61 (95% CI 0.37 to 1.00; p=0.052) for LLDAS-5 and 0.73 (95% CI 0.39 to 1.37; p=0.332) for LLDAS-7.5. Multivariable RRs were 0.56 (95% CI 0.37 to 0.86; p=0.007) and 0.47 (95% CI 0.27 to 0.85; p=0.012), respectively, with similar model fit. Among incident cases, 29/105 patients accrued damage (29 occasions); both LLDAS-5 (RR 0.31, 95% CI 0.11 to 0.89; p=0.029) and LLDAS-7.5 (RR 0.29, 95% CI 0.09 to 0.93; p=0.036) were associated with lower damage accrual.</p><p><strong>Conclusion: </strong>Longer time in LLDAS-5 was robustly associated with less damage accrual. Crude full-cohort analyses suggested a numerically stronger inverse association and slightly better model fit for LLDAS-5, but this apparent advantage was not sustained after multivariable adjustment. These findings support LLDAS-5 as a clinically meaningful, guideline-aligned target, while its incremental prognostic value over conventional LLDAS-7.5 requires further study.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031436","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":"Early SLE may follow a fast comorbidity/multimorbidity trajectory associated with flare burden and glucocorticoid exposure.","authors":"Myrto Nikoloudaki, Sofia Pitsigavdaki, Spyridon Katechis, Ettore Silvagni, Argyro Repa, Antonio Marangoni, Irini Flouri, Nestor Avgoustidis, Prodromos Sidiropoulos, Marcello Govoni, Antonis Fanouriakis, Alessandra Bortoluzzi, Dimitrios Boumpas, George Bertsias","doi":"10.1136/rmdopen-2026-007076","DOIUrl":"10.1136/rmdopen-2026-007076","url":null,"abstract":"<p><strong>Background: </strong>Patients with systemic lupus erythematosus (SLE) carry a substantial comorbidity load associated with worse prognosis, yet most evidence pertains to long-standing disease. How comorbidities-particularly multimorbidity as a marker of overall health burden-evolve at early stages, and whether conditions co-aggregate into clinically meaningful clusters, remains unclear.</p><p><strong>Methods: </strong>An inception cohort (≤2 years from diagnosis) of 311 patients with SLE with 5-year monitoring of 140 comorbidities, disease activity, treatments, organ damage and adverse events/hospitalisations. Growth mixture modelling identified trajectories of incident comorbidities, while tetrachoric exploratory factor analysis followed by clustering defined multimorbidity profiles; these trajectories and profiles were then related to longitudinal outcomes. To inform temporal ordering, trajectory modelling was refitted for months 24-60, and predictors from <24 months were evaluated using penalised multivariable regression.</p><p><strong>Results: </strong>Early SLE separated into slow (55%) and fast (45%) incident-comorbidity trajectories. Among fast accruers, three phenotypes emerged: low-to-moderate (general/non-patterned) (51%), metabolic-psychiatric (31%) and cardiopulmonary-musculoskeletal (18%), with a gradual increase in multimorbidity (≥2 conditions) (32.7%, 65.7% and 100%, respectively). Compared with slow-accruing, fast-accruing patients-especially the metabolic-psychiatric and cardiopulmonary-musculoskeletal-attained less lupus low disease activity state/Definition of Remission In SLE and developed more damage (incidence rate ratio (IRR) 2.28-3.27) and safety-related events (IRR 1.89-3.36). Severe flares (≥20% of time; OR 2.10, 95% CI 1.09 to 4.04) and glucocorticoid exposure (OR 1.06 per 10 mg/day, 95% CI 1.01 to 1.11) during the first 24 months independently predicted subsequent fast-comorbidity trajectory. Flares were more prominent in the fast/low-to-moderate and metabolic-psychiatric phenotypes, whereas glucocorticoid use was more prominent in the cardiopulmonary-musculoskeletal phenotype.</p><p><strong>Conclusions: </strong>Nearly half of patients with newly diagnosed SLE show accelerated comorbidity and multimorbidity burden, underscoring the need for clinical vigilance. Fast-accrual phenotypes are linked to flares and glucocorticoid exposure, two potentially modifiable features of early disease.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031450","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":"Temporal evolution of synovial histopathology in rheumatoid arthritis across treatment periods: a large-scale analysis of 1770 surgical specimens using the Rooney score.","authors":"Masanori Sudo, Asami Abe, Hajime Ishikawa, Sahoko Otsuka, Sayuri Takamura, Daisuke Kobayashi, Kiyoshi Nakazono, Akira Murasawa, Suguru Yamamoto, Satoshi Ito","doi":"10.1136/rmdopen-2026-007209","DOIUrl":"10.1136/rmdopen-2026-007209","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate temporal changes in rheumatoid arthritis (RA) synovial histopathology across treatment periods using the Rooney score in a surgical cohort.</p><p><strong>Methods: </strong>This retrospective study included 1770 synovial specimens from 1150 patients who underwent orthopaedic surgery between 2011 and 2025. Specimens were classified into early biological disease-modifying antirheumatic drug (bDMARD) (2011-2013), established bDMARD (2014-2018) and contemporary targeted therapy (2019-2025) periods. Mixed-effects models included patient-level random intercepts. Sensitivity analyses used calendar year, 3-year intervals, specimen-count-based tertiles and operated-joint power Doppler (PD) grade.</p><p><strong>Results: </strong>The median total Rooney scores were 29 (IQR 20-36), 24 (19.25-34) and 23 (20-32) across the periods (p for trend <0.001), driven by lower lymphocytic infiltration. The combined lymphocytic infiltration score decreased from 11 (0-20; early period) to 2 (0-11; contemporary period). After full adjustment, the contemporary period remained associated with a lower Rooney score than the early period (β -1.61, 95% CI -2.74 to -0.48; p=0.005). Tertile analyses were consistent, whereas adding operated-joint PD grade attenuated period estimates. Janus kinase (JAK) inhibitor-treated specimens did not have lower scores than bDMARD-treated specimens without JAK inhibitor exposure. Residual lymphocytic infiltration remained detectable despite clinical or imaging remission.</p><p><strong>Conclusions: </strong>RA synovial histopathology evolved across treatment periods, with lower Rooney scores and marked reductions in lymphocytic infiltration. These changes appear to reflect broader contemporary RA management rather than a JAK inhibitor-specific effect, although tissue-level inflammation may persist despite clinical or imaging remission.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"12 3","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149031360","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}