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If the evidence is there, why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients? 如果有证据,为什么GLP-1受体激动剂没有在标签上用于超重患者的髋关节和膝关节骨关节炎?
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-23 DOI: 10.1136/rmdopen-2025-006025
Francesco Ursini, Jacopo Ciaffi, Roberto Caporali
{"title":"If the evidence is there, why are GLP-1 receptor agonists not on-label for hip and knee osteoarthritis in overweight patients?","authors":"Francesco Ursini, Jacopo Ciaffi, Roberto Caporali","doi":"10.1136/rmdopen-2025-006025","DOIUrl":"10.1136/rmdopen-2025-006025","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have rapidly emerged as highly effective pharmacological tools for weight management, with additional cardiometabolic benefits extending beyond obesity and diabetes. Despite compelling evidence, their potential role in osteoarthritis (OA) remains unrecognized in current regulatory frameworks. Hip and knee OA, leading causes of disability and healthcare burden worldwide, are strongly influenced by both biomechanical overload and systemic metabolic-inflammatory pathways. Increasing data support the dual capacity of GLP-1 RAs to achieve clinically meaningful weight reduction and to exert direct anti-inflammatory and chondroprotective effects within the joint. The STEP 9 trial and complementary real-world evidence demonstrate substantial improvements in OA symptoms, paralleled by reductions in surgical risk, while ongoing trials such as STOP-KNEE OA will further clarify their structural impact. Importantly, patients with a body mass index (BMI) of 27-29.9 kg/m²-currently excluded from GLP-1 RA eligibility unless additional comorbidities are present-may particularly benefit, as weight loss beyond 7-10% appears necessary to meaningfully alter OA trajectories. Recognizing symptomatic hip and knee OA as weight-related comorbidities would align regulatory labels with emerging science, expand therapeutic access, and foster integrated management of musculoskeletal and metabolic diseases. This Viewpoint argues that failure to acknowledge OA as an on-label indication for GLP-1 RAs represents a missed opportunity for patients, clinicians, and health systems.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138679","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}
引用次数: 0
Longitudinal association of early axial spondyloarthritis status at the time of diagnosis with disease activity over time: 10-year results from the GESPIC cohort. 诊断时早期轴性脊柱炎状态与疾病活动性的纵向关联:来自GESPIC队列的10年结果
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-23 DOI: 10.1136/rmdopen-2025-005948
David Kiefer, Imke Redeker, Murat Torgutalp, Valeria Rios Rodriguez, Judith Rademacher, Fabian Proft, Mikhail Protopopov, Hildrun Haibel, Joachim Sieper, Martin Rudwaleit, Xenofon Baraliakos, Denis Poddubnyy
{"title":"Longitudinal association of early axial spondyloarthritis status at the time of diagnosis with disease activity over time: 10-year results from the GESPIC cohort.","authors":"David Kiefer, Imke Redeker, Murat Torgutalp, Valeria Rios Rodriguez, Judith Rademacher, Fabian Proft, Mikhail Protopopov, Hildrun Haibel, Joachim Sieper, Martin Rudwaleit, Xenofon Baraliakos, Denis Poddubnyy","doi":"10.1136/rmdopen-2025-005948","DOIUrl":"10.1136/rmdopen-2025-005948","url":null,"abstract":"<p><strong>Objective: </strong>Recently, the definition for 'early axial spondyloarthritis (axSpA)' was developed by the Assessment of SpondyloArthritis international Society (ASAS), including ≤2 years of axial symptoms as a key element. The aim of this study was to analyse the longitudinal association of early axSpA with achieving low disease activity or inactive disease.</p><p><strong>Methods: </strong>Using 10-year longitudinal data from the German Spondyloarthritis Inception Cohort (GESPIC), a generalised estimating equations model was fitted to estimate the effect of early axSpA on disease activity, as measured by the Axial Spondyloarthritis Disease Activity Score (ASDAS). The model adjusted for confounders identified through a directed acyclic graph and accounted for repeated measurements within patients. Additional analyses were conducted, including stratification by radiographic status (non-radiographic-nr or radiographic-r).</p><p><strong>Results: </strong>Of 525 patients (277 nr-axSpA, 248 r-axSpA) included in GESPIC, 161 (30%) fulfilled the ASAS early axSpA consensus definition (115 nr-axSpA and 46 r-axSpA) at baseline. Over the 10-year follow-up period, patients with early axSpA consistently achieved ASDAS states of inactive disease or low disease activity at a higher rate than those with non-early axSpA, rising from 41% versus 30% at baseline to 57% versus 44% at year 10. The total effect of early axSpA on ASDAS was -0.42 (95% CI: -0.57 to -0.26). Stratification by r-axSpA/nr-axSpA showed a total effect of -0.50 (95% CI: -0.81 to -0.19) for r-axSpA and -0.28 (95% CI: -0.46 to -0.10) for nr-axSpA.</p><p><strong>Conclusion: </strong>Fulfilment of the ASAS early axSpA definition at inclusion was associated with lower disease activity over 10 years.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138660","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}
引用次数: 0
Serum calprotectin and complement factor C3 are superior biomarkers of inflammation in early psoriatic arthritis as compared with C-reactive protein. 与c反应蛋白相比,血清钙保护蛋白和补体因子C3是早期银屑病关节炎炎症的优越生物标志物。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-23 DOI: 10.1136/rmdopen-2025-006019
Alla Ishchenko, Margot Van Mechelen, Sofia Pazmino, Lies Storms, Barbara Neerinckx, Patrick Verschueren, Rik Lories, Kurt de Vlam
{"title":"Serum calprotectin and complement factor C3 are superior biomarkers of inflammation in early psoriatic arthritis as compared with C-reactive protein.","authors":"Alla Ishchenko, Margot Van Mechelen, Sofia Pazmino, Lies Storms, Barbara Neerinckx, Patrick Verschueren, Rik Lories, Kurt de Vlam","doi":"10.1136/rmdopen-2025-006019","DOIUrl":"10.1136/rmdopen-2025-006019","url":null,"abstract":"<p><strong>Objectives: </strong>C reactive protein (CRP) is frequently normal in psoriatic arthritis (PsA) despite active disease, complicating inflammation assessment. This study aimed to evaluate alternative biomarkers of inflammation in early PsA.</p><p><strong>Methods: </strong>Adult patients with early, treatment-naïve PsA were enrolled in the prospective multicentre cohort and compared with early rheumatoid arthritis (RA) and healthy controls (HCs). Clinical assessments, inflammatory markers and peripheral blood counts were collected. For this study, baseline and 1-year data were used. Serum complement factor 3 (C3), calprotectin (S100A8/9) and serum amyloid A (SAA) were measured by ELISA. Discriminatory performance was evaluated using receiver operating characteristic curve analysis.</p><p><strong>Results: </strong>A total of 67 PsA, 50 RA patients and 61 HC were included. At baseline, median levels of C3 (1.38 g/L) and S100A8/9 (5.58 µg/mL) were significantly elevated in PsA compared with HC and were comparable to RA. In the 'CRP-negative' subgroup, C3 and S100A8/9 were increased in PsA as compared with HC. In the obese subgroup, CRP levels did not discriminate PsA, RA and HC. However, S100A8/9 was significantly increased in PsA and RA as compared with HC, whereas SAA and derived inflammatory ratios (neutrophil/monocyte ratio, lymphocyte/monocyte ratio) did not discriminate PsA, RA or HC. After 1 year, C3 and S100A8/9 decreased significantly in PsA patients achieving low disease activity. In the obese subgroup, the composite marker C3×calprotectin demonstrated superior diagnostic performance as compared with CRP (area under the curve=0.836).</p><p><strong>Conclusions: </strong>C3 and calprotectin are elevated in early PsA and are responsive to treatment. These markers outperform CRP in obese and CRP-negative patients and may support improved diagnosis and disease monitoring in clinical practice.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138688","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}
引用次数: 0
Assessment of the minimal clinically important difference for the Health Assessment Questionnaire Disability Index in patients with arthralgia at risk for progression to rheumatoid arthritis. 评估有进展为类风湿关节炎风险的关节痛患者健康评估问卷残疾指数的最小临床重要差异
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-21 DOI: 10.1136/rmdopen-2025-005899
Stijn Claassen, Hanna W van Steenbergen, Annette H M van der Helm-van Mil
{"title":"Assessment of the minimal clinically important difference for the Health Assessment Questionnaire Disability Index in patients with arthralgia at risk for progression to rheumatoid arthritis.","authors":"Stijn Claassen, Hanna W van Steenbergen, Annette H M van der Helm-van Mil","doi":"10.1136/rmdopen-2025-005899","DOIUrl":"10.1136/rmdopen-2025-005899","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with arthralgia at-risk for rheumatoid arthritis (RA) experience considerable functional disability, though generally less than at RA diagnosis. Secondary prevention trials have shown that treatment can improve disability in patients with arthralgia. However, interpreting the clinical relevancy of the improvements in Health Assessment Questionnaire Disability Index (HAQ-DI) is hampered by the lack of a defined minimal clinically important difference (MCID) in this disease stage. Results from other disciplines than rheumatology suggested that the MCID depends on absolute severity values. Therefore, we hypothesised that the MCID for HAQ-DI in RA depends on absolute values. We aimed to investigate this and, if so, to determine the MCID for disability in the risk setting.</p><p><strong>Methods: </strong>We studied the literature and determined the correlation of baseline HAQ-DI and MCID estimates in RA. To determine the MCID in arthralgia, we studied 97 patients treated with methotrexate in the TREAT EARLIER trial with HAQ-DI data at baseline and 12 months. At 12 months, a short-form 36 questionnaire anchor question compared patients' general health to that of 1 year before. The MCID was determined using the mean change in HAQ-DI score of patients reporting 'somewhat better' and 'somewhat worse'.</p><p><strong>Results: </strong>In RA, the MCID estimates ranged from -0.06 to -0.38, and higher absolute HAQ values correlated with a higher MCID. In the at-risk patients studied, the MCID for improvement was -0.07±0.28. Likewise, for deterioration, the MCID was +0.05±0.6.</p><p><strong>Conclusion: </strong>In arthralgia at-risk for RA, the MCID for improvement in HAQ-DI is -0.07. This is lower than generally reported in RA. This implies that in arthralgia, compared with RA, smaller improvements in HAQ-DI are clinically relevant.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125997","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}
引用次数: 0
Association between body weight fluctuation and progression of radiographic knee osteoarthritis: a longitudinal cohort study. 体重波动与膝骨关节炎影像学进展之间的关系:一项纵向队列研究。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-21 DOI: 10.1136/rmdopen-2025-005890
Kai Fu, Win Min Oo, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Yong Feng, Changqing Zhang, Qianying Cai, Changhai Ding, Flavia Cicuttini, David J Hunter
{"title":"Association between body weight fluctuation and progression of radiographic knee osteoarthritis: a longitudinal cohort study.","authors":"Kai Fu, Win Min Oo, Jean-Pierre Pelletier, Johanne Martel-Pelletier, Yong Feng, Changqing Zhang, Qianying Cai, Changhai Ding, Flavia Cicuttini, David J Hunter","doi":"10.1136/rmdopen-2025-005890","DOIUrl":"10.1136/rmdopen-2025-005890","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the relationship between body weight fluctuation and the progression of knee pain and joint space loss () in people with radiographic knee osteoarthritis (RKOA) during a 48-month follow-up period.</p><p><strong>Design: </strong>We conducted a longitudinal study using data from the Osteoarthritis Initiative. We analysed body weight variability through metrics of average successive variability (ASV), and residual ASV from baseline to 48 months. We assessed the impact of the fluctuations on changes in the Western Ontario and McMaster Universities Osteoarthritis Index pain scores and JSL, defined as a decrease of ≥0.7 mm in medial joint space width (JSW), using generalised estimating equations to account for correlation within-person and adjusted for covariates.</p><p><strong>Results: </strong>A total of 2993 and 2789 knees from 2051 participants were included in the pain and JSW analyses, respectively. Higher body weight variability correlated with increased knee pain but not JSL. Participants with high variability (ASV ≥2.07 kg) had a greater OR of aggravated knee pain (OR: 1.24, 95% CI: 1.01 to 1.51, MD: 0.30, 95% CI: 0.05 to 0.54), particularly among initially overweight or obese individuals (OR: 1.30, 95% CI: 1.05 to 1.62, MD: 0.35, 95% CI: 0.08 to 0.62) and those who gained over 3% body weight (OR: 1.54, 95% CI: 1.01 to 2.33, MD: 0.65, 95% CI: 0.16 to 1.14).</p><p><strong>Conclusions: </strong>Body weight fluctuations are a potential risk factor for symptom progression in RKOA, especially among overweight/obese individuals or those who gain weight. Maintaining a stable body weight may help alleviate the progression of symptoms related to knee osteoarthritis.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126038","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}
引用次数: 0
'Fast Ossifier' in diffuse idiopathic skeletal hyperostosis: a sex-modulated, heterogeneous phenotype with accelerated ossification and early trabecular decline. 弥漫性特发性骨骼增生的“快速骨化”:一种性别调节的异质性表型,骨化加速和早期小梁衰退。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-21 DOI: 10.1136/rmdopen-2025-006024
Emilio Pariente-Rodrigo, Marta Martín-Millán, Giusi Sgaramella, Javier Pardo-Lledías, Patricia Fierro-Andrés, Merelyn Bonome, Sandra Solares, Carmen Ramos-Barrón, José Manuel Olmos-Martínez, Victor Martínez-Taboada, José L Hernández
{"title":"'Fast Ossifier' in diffuse idiopathic skeletal hyperostosis: a sex-modulated, heterogeneous phenotype with accelerated ossification and early trabecular decline.","authors":"Emilio Pariente-Rodrigo, Marta Martín-Millán, Giusi Sgaramella, Javier Pardo-Lledías, Patricia Fierro-Andrés, Merelyn Bonome, Sandra Solares, Carmen Ramos-Barrón, José Manuel Olmos-Martínez, Victor Martínez-Taboada, José L Hernández","doi":"10.1136/rmdopen-2025-006024","DOIUrl":"10.1136/rmdopen-2025-006024","url":null,"abstract":"<p><strong>Background: </strong>Diffuse idiopathic skeletal hyperostosis (DISH) is considered a slowly progressive condition, typically requiring a decade to achieve full radiographic development. However, some individuals exhibit accelerated ossification. This study aimed to characterise the clinical profile of these patients, referred to as Fast Ossifiers (FO).</p><p><strong>Methods: </strong>Study nested within the Camargo Cohort, integrating cross-sectional and longitudinal data (baseline (E0), 5 year (E1) and 10 year assessments (E2)). Propensity Score matching was applied. FO was defined as progression of ≥2 grades in Schlapbach's Scale between consecutive assessments. We evaluated inflammation, insulin resistance (via Triglyceride-Glucose Index (TyG)), Visceral Adiposity Index (VAI), intact parathormone (iPTH), bone turnover markers and Trabecular Bone Score (TBS).</p><p><strong>Results: </strong>We analysed 455 DISH cases and 455 matched controls. During follow-up, 61 individuals fulfilled FO criteria (18%<60 years; 49% female; 65.6% obese; 72.1% hypertensive). Compared with controls, FO subjects had higher TyG (8.65±0.9 vs 8.39±0.4; p=0.002), FO-females showed higher visceral adiposity (VAI 2.30±2 vs 1.44±0.1; p=0.024), and both sexes presented elevated iPTH at E2. In multivariable models, FO was associated with high TyG (adjusted OR=9.31; 95% CI: 1.04 to 36; p=0.046), low TBS (adjusted OR=0.002; 95% CI: 0.001 to 0.61) and higher alkaline phosphatase levels (79 vs 69 (U/L); p=0.043).</p><p><strong>Conclusions: </strong>FO represents an active variant that challenges the view of DISH as a quiescent disease affecting older men. Rather than a single entity, FO emerges as a convergent phenotype driven by diverse metabolic pathways and linked to accelerated skeletal changes, including ossification and early trabecular impairment.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126056","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}
引用次数: 0
Are investigator-initiated clinical trials becoming an 'endangered species'? 研究者发起的临床试验正在成为“濒危物种”吗?
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-18 DOI: 10.1136/rmdopen-2025-006151
Helena Marzo-Ortega, Gabriele De Marco
{"title":"Are investigator-initiated clinical trials becoming an 'endangered species'?","authors":"Helena Marzo-Ortega, Gabriele De Marco","doi":"10.1136/rmdopen-2025-006151","DOIUrl":"10.1136/rmdopen-2025-006151","url":null,"abstract":"","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092428","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}
引用次数: 0
Active vitamin D acts in vitro as an adjuvant to anti-TNFα treatment in a psoriatic synovial fibroblast activation model by modulating human Th17 activity. 活性维生素D通过调节人Th17活性在银屑病滑膜成纤维细胞活化模型中作为抗tnf α治疗的辅助剂。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-18 DOI: 10.1136/rmdopen-2025-005547
Yi He, Bennie Van Heeswijk, Adriana M C Mus, Nadine Davelaar, Radjesh Bisoendial, Erik Lubberts
{"title":"Active vitamin D acts in vitro as an adjuvant to anti-TNFα treatment in a psoriatic synovial fibroblast activation model by modulating human Th17 activity.","authors":"Yi He, Bennie Van Heeswijk, Adriana M C Mus, Nadine Davelaar, Radjesh Bisoendial, Erik Lubberts","doi":"10.1136/rmdopen-2025-005547","DOIUrl":"10.1136/rmdopen-2025-005547","url":null,"abstract":"<p><strong>Objectives: </strong>Psoriatic arthritis (PsA) is an IL-23/IL-17/TNF-driven inflammatory arthritis, commonly accompanied by vitamin D deficiency. Here, we investigate the interaction between PsA synovial fibroblasts (SFs) and human memory CCR6+Th17 (hmemCCR6+Th17) cells and evaluate the therapeutic effects of TNFα and/or IL-17A inhibitors, and the adjunctive therapy potential of 1,25-dihydroxyvitamin D3 (1,25(OH)<sub>2</sub>D<sub>3</sub>).</p><p><strong>Methods: </strong>SF derived from PsA biopsies were co-cultured with hmemCCR6+Th17 cells to construct a PsA SF activation model. SF phenotypes were analysed by flow cytometry. Treatments included adalimumab (anti-TNFα), secukinumab (anti-IL-17A), and/or 1,25(OH)<sub>2</sub>D<sub>3</sub>, applied alone or in combination. A transwell system was used to assess treatment effects on SF and hmemCCR6+Th17 cells. Cytokines and matrix metalloproteinases (MMPs) were quantified by ELISA.</p><p><strong>Results: </strong>PsA SF were composed of heterogeneous subpopulations and constructed a pro-inflammatory feedback loop with hmemCCR6+Th17 cells. Anti-TNFα and/or anti-IL-17A significantly suppressed proinflammatory cytokines and tissue-destructive mediators in the PsA SF activation model, but showed limited effect on IL-22 and IFNγ. Adding 1,25(OH)<sub>2</sub>D<sub>3</sub> to anti-TNFα treatment effectively overcame the limitations of single anti-TNFα in suppressing Th17 cytokines, while significantly enhancing the inhibition of IL-6, IL-8 and MMPs. In addition, 1,25(OH)<sub>2</sub>D<sub>3</sub> promoted the production of IL-10.</p><p><strong>Conclusions: </strong>TNFα or IL-17A inhibition alone does not completely inhibit the proinflammatory loop between hmemCCR6+Th17 cells and PsA SF, although the combination shows additive effect on suppressing proinflammatory and tissue-destructive mediators. Importantly, 1,25(OH)<sub>2</sub>D<sub>3</sub> plays a complementary role in the treatment of this proinflammatory loop alongside anti-TNFα therapy and significantly induces IL-10. Clinical PsA studies are needed to explore the additional therapeutic potential of this combination.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092461","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}
引用次数: 0
Distribution of nailfold videocapillaroscopy parameters in systemic lupus erythematosus and their association with disease activity: an international blinded case-control analysis on behalf of the EULAR study group on microcirculation in rheumatic diseases. 系统性红斑狼疮患者甲襞视频毛细血管镜参数的分布及其与疾病活动性的关系:代表EULAR风湿病微循环研究组进行的一项国际盲法病例对照分析。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-08 DOI: 10.1136/rmdopen-2025-005772
Francesca Ingegnoli, Nicola Ughi, Valeria Riccieri, Katia Stefanantoni, Jean-Luc Cracowski, Marwin Gutierrez, Alberto Sulli, Tatiana S Rodriguez-Reyna, Alexandra Hame, Ashima Makol, Laura Nuño-Nuño, Juan Carlos Nieto-Gonzalez, Satoshi Kubo, Malgorzata Michalska-Jakubus, Olga Sanchez Pernaute, Rossella De Angelis, Ariane L Herrick, Karin Melsens, Maurizio Cutolo, Vanessa Smith
{"title":"Distribution of nailfold videocapillaroscopy parameters in systemic lupus erythematosus and their association with disease activity: an international blinded case-control analysis on behalf of the EULAR study group on microcirculation in rheumatic diseases.","authors":"Francesca Ingegnoli, Nicola Ughi, Valeria Riccieri, Katia Stefanantoni, Jean-Luc Cracowski, Marwin Gutierrez, Alberto Sulli, Tatiana S Rodriguez-Reyna, Alexandra Hame, Ashima Makol, Laura Nuño-Nuño, Juan Carlos Nieto-Gonzalez, Satoshi Kubo, Malgorzata Michalska-Jakubus, Olga Sanchez Pernaute, Rossella De Angelis, Ariane L Herrick, Karin Melsens, Maurizio Cutolo, Vanessa Smith","doi":"10.1136/rmdopen-2025-005772","DOIUrl":"10.1136/rmdopen-2025-005772","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate whether patients with systemic lupus erythematosus (SLE) have different nailfold videocapillaroscopy (NVC) findings compared with healthy controls (HCs) and whether there is an association between NVC abnormalities and disease activity, clinical and/or laboratory features in SLE.</p><p><strong>Methods: </strong>This is an observational, multicentre, international, matched case-control study. 381 subjects (203 patients with SLE and 178 HCs) were enrolled from 16 centres in 10 countries. Clinical and laboratory data were collected using ad hoc forms. 5861 NVC images were acquired, coded and uploaded for central blinded analysis.</p><p><strong>Results: </strong>A normal NVC pattern was observed in most patients with SLE (86.6%) and, a significantly higher frequency of NVC abnormalities such as enlarged and giant capillaries, microhaemorrhages and irregular nail bed architecture (p<0.001) were found in the remaining patients. Multiple correspondence analysis outlined two NVC patterns, one of which, the more severe (cluster 2), present in 12% of patients, was characterised by a higher prevalence of lower capillary density, abnormally shaped and enlarged capillaries and irregular nail bed architecture. NVC cluster 2 had significantly higher disease activity compared with cluster 1 for both Systemic Lupus Erythematosus Disease Activity Index cut-off points ≥3 and ≥4 (p=0.016 and p=0.028, respectively). SLE with 'more severe' NVC pattern (cluster 2) have a significantly higher frequency of arthritis, renal involvement and ongoing glucocorticoid therapy, whereas serositis was significantly associated with 'less severe' NVC pattern (cluster 1).</p><p><strong>Conclusions: </strong>This study has shown that changes in NVC patterns are associated with important aspects of SLE disease activity. Future prospective studies are needed to further support the use of NVC in SLE monitoring.</p><p><strong>Trial registration number: </strong>NCT02801812.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12421155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024183","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}
引用次数: 0
Accrual of thromboembolic events and antiphospholipid syndrome in new-onset systemic lupus erythematosus: a population-based inception cohort study. 新发系统性红斑狼疮患者血栓栓塞事件和抗磷脂综合征的累积:一项基于人群的初始队列研究。
IF 4.7 2区 医学
RMD Open Pub Date : 2025-09-02 DOI: 10.1136/rmdopen-2025-005795
Sigrid Reppe Moe, Hilde Haukeland, Cathrine Brunborg, Antonela Botea, Nenad Damjanic, Gro Årthun Wivestad, Heidi Kverneggen Øvreås, Thea Bjerkestrand Bøe, Anniken Orre, Garen Torhild, Sella Aarrestad Provan, Øyvind Molberg, Karoline Lerang
{"title":"Accrual of thromboembolic events and antiphospholipid syndrome in new-onset systemic lupus erythematosus: a population-based inception cohort study.","authors":"Sigrid Reppe Moe, Hilde Haukeland, Cathrine Brunborg, Antonela Botea, Nenad Damjanic, Gro Årthun Wivestad, Heidi Kverneggen Øvreås, Thea Bjerkestrand Bøe, Anniken Orre, Garen Torhild, Sella Aarrestad Provan, Øyvind Molberg, Karoline Lerang","doi":"10.1136/rmdopen-2025-005795","DOIUrl":"10.1136/rmdopen-2025-005795","url":null,"abstract":"<p><strong>Objective: </strong>This population-based study aimed to determine timing and incidence of arterial and venous thromboembolic events (TE) and antiphospholipid syndrome (APS) relative to systemic lupus erythematosus (SLE) onset and assess relationships between TE, APS and anti-phospholipid antibodies (aPL) during follow-up.</p><p><strong>Methods: </strong>We included all medical-record confirmed new-onset SLE patients in Southeast Norway (population 2.9 million) 2000-2017 who fulfilled the 2019 European Alliance of Rheumatology Associations/American College of Rheumatology classification criteria. APS was defined by the 2006 Sydney classification criteria, and aPL positivity was determined following international guidelines. Key outcomes were APS, TE and death. We estimated outcome-free survival using Kaplan-Meier methods.</p><p><strong>Results: </strong>Among 700 new-onset SLE patients followed for a mean of 8 years (SD 5.0), 13% (89/700) experienced a new TE. TE incidence peaked at 59 per 100 person-years (95% CI 38 to 87) in the first year of SLE among aPL positive patients diagnosed with APS, falling to 12 (95% CI 6.2 to 21) in the subsequent 4 years. In patients without APS, corresponding TE incidences were 2.6 (95% CI 1.4 to 4.3) and 0.9 (95% CI 0.5 to 1.4), respectively. The lowest TE incidence was in aPL-negative patients aged <50 years, with 1-year TE-free survival of 0.99 (95% CI 0.97 to 1.0). Beyond the first year, TE-free survival rates did not differ between SLE patients positive and negative for aPL. Standardised mortality rate in patients with and without APS was 4.7 (95% CI 1.8 to 10.7 and 1.7 (95% CI 1.2 to 2.3).</p><p><strong>Conclusions: </strong>This population-level study reveals high risk of TE, particularly for aPL positive patients around the time of SLE diagnosis. The elevated TE risk requires attention and early preventive strategies in newly diagnosed SLE.</p>","PeriodicalId":21396,"journal":{"name":"RMD Open","volume":"11 3","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993476","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}
引用次数: 0
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