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Introduction: Clinical expertise is paramount in medical decision-making. In the setting of arthralgia, this expertise is highly relevant in differentiating clinically suspect arthralgia (CSA) from other musculoskeletal symptoms. However, it remains unclear whether rheumatological expertise is also reliable in estimating the risk of progression to rheumatoid arthritis (RA) in CSA patients. Using clinical expertise is more time-efficient than applying criteria, such as the European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) risk stratification criteria for RA development. This study assessed the accuracy of RA-risk estimation based on rheumatologists' clinical expertise and compared this to these criteria.

Methods: 501 CSA patients from the Leiden CSA cohort and placebo arm of the TREAT EARLIER trial were studied. At baseline, rheumatologists estimated RA risk (0-10 Numeric Rating Scale) informed by history, physical examination and laboratory results. The EULAR/ACR risk stratification criteria (without imaging) were calculated using baseline data. The outcome was RA development (2010 criteria) within 1 year, and the discrimination was compared.

Results: Based on their expertise, rheumatologists estimated the risk of RA as a mean of 5 (SD 1.6) on a 0-10 scale. With an area under the curve (AUC) of 0.64 (95% CI 0.55 to 0.73), patients who did or did not develop RA were moderately differentiated. The RA risk was mainly overestimated compared with observed progression rates. In comparison, the EULAR/ACR risk stratification criteria in the same patients yielded an AUC of 0.91 (95% CI 0.87 to 0.95).

Conclusions: Rheumatologists' clinical expertise is inaccurate in assessing the risk of developing RA in patients with CSA, due to risk overestimation. This may support the use of established criteria when risk information has clinical or therapeutic implications.

Trial registration number: NTR4853-trial-NL4599.

Objective: Anaemia is common in rheumatoid arthritis (RA), but the role of erythroid-lineage cells is unclear. We investigated the function of CD45⁺ erythroid progenitor cells (CD45⁺ EPCs) in RA.

Methods: We analysed CD45⁺ EPC frequency in patients with RA and mice with collagen-induced arthritis (CIA). Transcriptomics, functional studies and mechanistic assays (Transwell and dual-luciferase reporter assays, chromatin immunoprecipitation followed by quantitative PCR) were used. Therapeutic potential was tested in RA synovial organoids and via splenectomy/adoptive transfer in mice with CIA.

Results: CD45⁺ EPCs were expanded in RA circulation and CIA mouse spleens, correlating positively with disease activity and negatively with haemoglobin. They displayed an immunosuppressive transcriptome, enriched for transforming growth factor (TGF)-β and chemokine signalling. RA-derived CD45⁺ EPCs showed enhanced proliferation and TGF-β/reactive oxygen species production. High C-C Motif Chemokine Receptor 2 (CCR2) expression made them susceptible to recruitment by macrophage-derived C-C Motif Chemokine Ligand 2 (CCL2). In RA synovial organoids, CD45⁺ EPCs suppressed growth and inflammation via TGF-β, while organoid-conditioned media promoted their migration via CCL2. Recruited CD45⁺ EPCs suppressed M1 and promoted M2-like macrophage polarisation. The transcription factor SPI1 was upregulated in RA CD45⁺ EPCs, bound the TGFB1 promoter and drove TGF-β production. In vivo, splenectomy worsened CIA, whereas adoptive transfer of CD45⁺ EPCs ameliorated arthritis.

Conclusion: We identify CD45⁺ EPCs as a novel, SPI1-driven immunosuppressive population in RA. Recruited via the CCR2-CCL2 axis, they attenuate inflammation by modulating macrophages through SPI1/TGF-β signalling, revealing a new immunoregulatory axis and potential therapeutic targets.

Introduction: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Colchicine is the first-line treatment, yet 5-10% of patients are resistant, increasing the risk of complications like amyloidosis. In 2023, Batu et al proposed the Turkish Paediatric Autoinflammatory Diseases (TURPAID) score to predict colchicine resistance in paediatric FMF at diagnosis. Its utility in broader populations is unknown. We assessed its performance in paediatric and adult FMF patients from the international Juvenile Inflammatory Rheumatism (JIR) cohort.

Methods: We retrospectively analysed 236 genetically confirmed FMF patients treated with colchicine for ≥6 months. Patients were classified as colchicine-sensitive (CoS) or colchicine-resistant (CoR) based on the initiation of biologic therapy, which served as an operational definition of resistance, and matched for age and sex. The TURPAID score (range 0-4; resistance threshold ≥2) was retrospectively applied. Receiver operating characteristic (ROC) curves were used to assess predictive value.

Results: A TURPAID score ≥2 was observed in 89% of paediatric and 76% of adult CoS patients. Mean scores were significantly higher in paediatric-onset FMF. ROC analysis showed poor discrimination in both paediatric and adult groups (area under the curve=0.6). Clinical features and attack patterns varied by age. The genetic component (1.5 points for MEFV exon 10 mutations) contributed to overclassification, reducing predictive accuracy.

Conclusion: The TURPAID score did not effectively predict colchicine resistance in the JIR cohort. Its limited generalisability may stem from age-related differences, recall bias and excessive genetic weighting. Genetic results should be a prerequisite and not a determinant of colchicine resistance prediction scores in FMF.

Objective: To provide an overview of the effects of exercise for osteoarthritis.

Design: Overview.

Data sources: Medline, Embase, Epistemonikos, PEDro, Cochrane and registries from inception to 8 November 2025.

Eligibility criteria: Reviews comparing exercise with placebo, no intervention or other interventions on pain and function for osteoarthritis. Supplementary trials were included to update inconclusive areas.

Data extraction and synthesis: Two independent reviewers extracted data and assessed bias. Data were standardised to a 0-100 scale and reanalysed using random-effects meta-analysis. Certainty was rated using Grading of Recommendations Assessment, Development and Evaluation.

Results: Five reviews (κ=100; n=8631) and 28 supplementary trials (knee/hip κ=23, hand κ=3, ankle κ=2; n=4360) were included. Evidence indicated small, short-term effects of exercise versus placebo (mean difference -10.8, 95% CI -19.1 to -2.6) and no-treatment (-12.4, 95% CI -15.6 to -9.2) for knee osteoarthritis pain, but certainty was very low and effects in larger or longer-term trials were smaller. Moderate evidence suggested negligible effects in hip (-6.7 95% CI -9.3 to -4.0) and small effects in hand (-10.0 95% CI -15.5 to -4.5) osteoarthritis. Varying certainty evidence indicated comparable outcomes to education, manual therapy, analgesics, injections and arthroscopy. Single trials in selected populations showed exercise was less effective than knee osteotomy (12.4 95% CI 4.7 to 20.2) and joint replacement (knee 17.1 95% CI 10.4 to 23.8; hip 24.2 95% CI 18.2 to 30.2) at longer term.

Conclusion and relevance: Evidence on exercise for osteoarthritis remains largely inconclusive, suggesting negligible or short-lasting small effects comparable to, or less effective than, other treatments. These findings question its universal promotion and highlight the need to revisit research priorities and clinical discussions around its worthwhileness.

Registration: CRD42023446888.

Objectives: Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a systemic autoimmune disease where infections can trigger relapses. Dental infections, being common and associated with systemic inflammation, may play a role in AAV relapse, though their impact remains unclear. We aimed to evaluate the association between severe dental infections and early relapse in patients with AAV.

Methods: This retrospective cohort study included patients newly diagnosed with AAV between January 2011 and July 2022. Patients with severe dental infections requiring tooth extraction were placed in the dental infection group, while the remaining patients were assigned to the control group. The primary outcome was defined as either vasculitis relapse or all-cause mortality within 1 year of treatment initiation. Adjusted HRs (aHRs) and 95% CIs were estimated using Cox proportional hazards models.

Results: A total of 93 patients were enrolled with a median age of 74 years. 41 patients (44.1%) had severe dental infections in this cohort. Over the 1-year follow-up period, 13 patients experienced a relapse and two died, resulting in a composite event rate of 20.9 per 100 person-years. Dental infection was independently associated with the composite outcome (aHR, 3.78 (95% CI 1.13 to 12.66); p=0.031). Exploratory analysis indicated that composite outcome rates were similar regardless of tooth extraction among patients with dental infections.

Conclusions: Severe dental infections were associated with increased risk of early relapse or mortality in AAV. These findings highlight the importance of early dental evaluation in AAV management.

Objective: To assess the impact of medium-chain triglycerides (MCTs) and fibre on health-related quality of life (QOL), morning stiffness and pain in rheumatoid arthritis (RA) patients.

Methods: A randomised, double-blind, placebo-controlled clinical trial enrolled 61 RA patients on stable drug treatment. Participants received twice-daily MCT supplementation (30 g/day) for 8 weeks, followed by 8 weeks of MCTs (30 g/day) combined with fibre (30 g/day). The control group received the same supplementation as the test group, with long-chain triglycerides instead of MCTs. QOL parameters, morning stiffness, pain intensity and lipid profile were assessed at baseline (T0), week 8 (T2) and week 16 (T4).

Results: After 16 weeks, the test group showed statistically and clinically significant improvements both in mental and physical health-related scores. MCT consumption significantly ameliorated mental health, emotional well-being, social behaviour and vitality (measured using 36-Item Short Form Survey) from baseline to T4 and relative to control. An increased motivation, as assessed with the Multidimensional Fatigue Inventory-20 questionnaire, was reported as well. Regular intake of MCTs significantly reduced the intensity and duration of morning stiffness and pain intensity (assessed using the Visual Analogue Scale) from baseline to T4 compared with control group. Reported effects were maintained after adding fibre to supplementation. Baseline blood lipid profile showed no significant differences.

Conclusions: Patients with RA supplemented with MCTs obtained significant improvements in several health-related QOL components compared to control, and fibre inclusion did not interfere with MCT efficacy. These results underscore the importance of targeted non-pharmacological approaches integrated to drug therapy in managing patients with RA.

Trial registration number: DRKS00025413.

Objectives: We aimed to develop a new complex intervention, the 'COuld it Be RA' (COBRA) tool, to support the implementation of a clinical prediction model to identify people likely to be anti-cyclic citrullinated peptide (CCP) positive and at risk of rheumatoid arthritis in primary care.

Methods: The COBRA tool was developed using the UK Medical Research Council and National Institute for Health and Care Research complex intervention research framework. This study involved three sequential phases with primary care clinicians: a qualitative descriptive study, clinician consultation engagement workshops and a think-aloud interview study. Ethical approval was obtained for all three phases.

Results: Sixteen primary care clinicians participated in semistructured interviews to identify barriers and facilitators. An initial list of nine candidate components for the intervention, including design considerations, was developed. During phase 2 workshops with eight participants, four components were prioritised as 'Must have' or 'Should have': the clinical decision support system (CDSS); guidance on using the CDSS/associated actions; evidence for the CDSS; patient education resources. A COBRA tool prototype incorporating these components was developed.Twelve participants tested the prototype during think-aloud interviews. Key perceived benefits of the COBRA tool included supporting clinicians' decision-making and reducing unnecessary anti-CCP testing. Over 40 changes were made to the COBRA tool.

Conclusion: Our research included the views of clinicians and PPI representatives and was underpinned by a complex intervention research framework. This was critical to understanding barriers and facilitators to implementing the clinical prediction model in primary care and developing the COBRA tool.

Background: Myositis-associated interstitial lung disease (MAILD) is one of the most severe complications of idiopathic inflammatory myopathy, characterised by rapidly progressive pulmonary fibrosis and high mortality. Treatment options are limited, and mechanisms driving epithelial-mesenchymal transition (EMT) in MAILD are incompletely understood. Anlotinib, a multitarget tyrosine kinase inhibitor, shows potential in fibrotic diseases; however, its role and mechanism in MAILD need clarification.

Methods: To assess anlotinib's therapeutic effects, we established a MAILD mouse model and a neutrophil extracellular trap (NET)-induced human alveolar epithelial cell (A549) model. H&E and Masson staining analysed lung pathological changes and collagen deposition. Immunohistochemistry, immunofluorescence and Western blot detected expressions of NETs markers (myeloperoxidase, citrullinated histone H3), phosphatidylinositol 3-kinase/protein kinase B (PI3K)/Akt components and EMT markers (E-cadherin, α-smooth muscle actin). RNA sequencing and gene set enrichment analysis identified differentially expressed genes and signalling pathways. Cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and wound healing assays assessed cellular repair and migration.

Results: MAILD mouse lungs showed structural damage, inflammatory infiltration, collagen deposition, increased NETs formation, PI3K/Akt activation and enhanced EMT. Anlotinib significantly ameliorated pulmonary fibrosis and reduced pro-inflammatory cytokines (tumour necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β). In vivo and in vitro, anlotinib suppressed NETs formation, PI3K/Akt activation and EMT, while enhancing alveolar epithelial cell repair and migration.

Conclusion: Anlotinib alleviates MAILD progression by inhibiting the NETs-PI3K/Akt axis and subsequent EMT, providing a theoretical basis for drug repurposing and supporting its clinical translation potential in MAILD.

Background: The aim of this systematic review and meta-analysis was to examine autoantibody positive individuals and define: (a) the relative risk of rheumatoid arthritis (RA) compared with autoantibody negative individuals and (b) the cumulative incidence of RA over time, in different populations.

Methods: A systematic literature search was performed in August 2025. Retrospective case control studies of individuals with RA and healthy matched controls were identified and relative risk of RA was calculated. Prospective observational studies or randomised controlled trials of autoantibody positive individuals were identified and pooled survival models were used to estimate cumulative incidence of progression to arthritis.

Results: 293 full-text articles fulfilled screening criteria and 26 were eligible for meta-analysis. The presence of serum autoantibodies confers between a 3.1--19.3-fold increase risk of developing RA. Prospective studies of anticyclic citrullinated peptide 2 (CCP2) or CCP3 positive individuals were grouped according to additional criteria; presence of arthralgia, presence/absence of immunoglobulin M rheumatoid factor (IgM-RF) and first-degree or second-degree relatives with RA. The estimated cumulative incidence of RA at 12 months was highest for CCP2 positive individuals with arthralgia and IgM-RF, at 35.2% (95% CI 29.3% to 41.2%).

Conclusion: A considerable number of autoantibodies have been examined as predictors for RA; however, the fastest rate of progression to RA in this study occurred in those with CCP2 and IgM-RF in combination with arthralgia. Importantly, the risk of developing RA changes over time for individuals with arthralgia, and they are at the highest risk of progression within the first 24 months of follow-up.

Prospero registration number: CRD42021231245.