Para médicos · reumatologia
Resumos de artigos, podcasts e newsletters sobre Artrite Reumatoide, para atualização médica.
A newsletter aborda o manejo do risco cardiovascular na artrite reumatoide e a eficácia de terapias sequenciais com romosozumabe e denosumabe para prevenir a perda óssea em usuários de corticoides. Além disso, discute o uso de doses reduzidas de rituximabe em AR soropositiva e a correlação entre sinovite e progressão radiográfica na osteoartrite de mãos.
A newsletter discute como a obesidade atenua a resposta aos inibidores de JAK na artrite reumatoide, enfatizando que o IMC elevado é um modificador de efeito clínico relevante. O conteúdo também aborda a alta prevalência de critérios de fibromialgia em pacientes pós-COVID, a conduta expectante na artrite por parvovírus B19 e a associação genética entre regulação tireoidiana e deposição de cristais de pirofosfato de cálcio.
A newsletter destaca a revisão do índice de dano (SDI) no Lúpus Eritematoso Sistêmico, que busca maior precisão clínica ao remover itens de atividade inflamatória e incluir critérios de gravidade. Além disso, apresenta novos guidelines da EULAR para vasculites e polimialgia reumática, e discute evidências recentes sobre terapias biológicas e inibidores de fosfodiesterase em doenças autoimunes.
A newsletter discute as novas diretrizes do ACR 2025 para o lúpus eritematoso sistêmico, enfatizando a importância da ultrassonografia para identificar sinovites frequentemente subestimadas no exame clínico. O conteúdo detalha o desempenho de terapias como anifrolumabe e belimumabe em diferentes perfis de pacientes, além de abordar a aprovação do anacinra e casos de fraturas por insuficiência na artrite reumatoide.
OBJECTIVE: People with inflammatory arthritis (IA) frequently experience work instability, absenteeism, and reduced productivity, culminating in early job loss. This study evaluated the effectiveness and cost-effectiveness of WORKWELL job retention vocational rehabilitation (JRVR) delivered by occupational therapists, compared to a control group receiving written self-help advice. METHODS: A pragmatic, multi-centre randomised controlled trial was conducted across 18 UK NHS Trusts. Employed adults (n = 249) with IA experiencing moderate to severe work instability, were randomised (1:1) to intervention or control groups. WORKWELL included structured work assessment, individually tailored action plans, and interventions over 2-4 months. Follow-up was at 6, 12, and 36 months. The primary outcome was the Work Limitations Questionnaire-25 (WLQ-25). Analyses used linear mixed-effects regression adjusted for baseline characteristics and occupational skill level. An NHS perspective was used for the within-trial cost-effectiveness analysis. Much of the trial was affected by the COVID-19 pandemic. RESULTS: At 12 months, there was no significant difference in WLQ-25 between groups (adjusted mean difference: -1.8; 95% CI -7.4 to 3.8; p = 0.53), or in most secondary outcomes at 12- or 36-months. However, absenteeism showed a relative reduction of 46% at 12 months (p = 0.08), and employment retention at 36 months was higher in the intervention (93%) vs. control group (85%). The intervention was not cost-effective from an NHS perspective. CONCLUSION: WORKWELL did not lead to improved work productivity compared to self-help advice. Future research should explore more flexible delivery methods, including digital tools, to support sustainable employment for people with IA. A plain-language abstract is available in the supplementary material. TRIAL REGISTRATION: ClinicalTrials.gov; NCT03942783. ISRCTN Registry; ISRCTN61762297.
Rheumatoid arthritis (RA) is a biologically heterogeneous immune-mediated disease characterized by substantial variability in therapeutic response. Despite the availability of multiple conventional synthetic, biologic, and targeted synthetic disease-modifying antirheumatic drugs (DMARDs), many patients fail to achieve adequate disease control or experience secondary loss of efficacy, underscoring the need for predictive biomarkers that can guide treatment selection. This narrative review was based on a structured literature search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, covering publications from January 2000 to June 2026, with earlier landmark studies included when relevant. Literature selection followed PRISMA-informed principles, although the review was not designed as a formal systematic review. Unlike previous reviews that mainly catalogue RA biomarkers by analytical platform, drug class, or clinical use, this review integrates conventional and emerging biomarkers within a tissue-immunophenotype-centered framework. We critically evaluate clinical, serological, pharmacological, molecular, imaging, and tissue-based biomarkers according to biological plausibility, reproducibility, level of validation, clinical actionability, and translational readiness. Established markers such as rheumatoid factor, anti-citrullinated protein antibodies, acute-phase reactants, drug concentrations, and anti-drug antibodies remain clinically useful but provide incomplete insight into mechanism-specific therapeutic response. In contrast, synovial pathotypes, fibroblast and macrophage subsets, B-cell niches, tertiary lymphoid structures, single-cell and spatial omics, and ligand–receptor interaction networks offer a mechanistically richer view of treatment response and resistance. We conclude that precision medicine in RA will require integrated biomarker panels combining clinical, pharmacological, molecular, and synovial tissue data. The key future direction is the development of scalable, externally validated, and clinically interpretable models capable of assigning synovial endotypes and supporting mechanism-based therapeutic selection.
This study aimed to investigate the relationship between cognitive performance and the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA), emphasizing the role of plasma metabolites and proteins. Using National Health and Nutrition Examination Survey 2011 to 2014 data, cognitive functions of participants aged >60 years were evaluated, examining their correlation with OA and RA. Covariates, including demographics and health-related factors, were included. Genetic causality was determined using Mendelian randomization with single-nucleotide polymorphisms from the UK Biobank and other datasets. Linkage disequilibrium score regression and colocalization analyses were performed to validate genetic correlations and identify shared genetic variants. Cognitive performance was assessed in 387 and 237 OA and RA patients, respectively, compared with 1569 controls. OA patients had significantly lower Consortium to Establish a Registry for Alzheimer's Disease-4 cognitive scores (odds ratio [OR]: 0.962, P = .001), while RA patients had lower digit symbol substitution test scores (OR: 0.980, P = .001). Mendelian randomization revealed a negative causal association between cognitive performance and OA (OR: 0.767, P = .001) and RA (OR: 0.712, P = .006). Plasma components, including bone sialoprotein 2, NKP44, and the metabolite X-11478, were causally linked to cognitive performance. Mediation analysis identified mediators, including FGR and 6CKine. Linkage disequilibrium score regression revealed a genetic correlation between cognitive performance and OA and RA, with colocalization analysis identifying shared genetic factors. GDF5 and TRAIP were associated with OA, and EHMT2 with RA. Cognitive factors, influenced by plasma components, may influence OA and RA onset. This relationship highlights the need for integrated interventions targeting cognitive function and joint health.
OBJECTIVE: Care complexity represents the intersection of health status and social determinants of health, which can impact patient care and outcomes. People living with rheumatoid arthritis (PlwRA) experiencing care complexity may require longer healthcare appointments or more frequent healthcare visits or services. This review identified RA-related care complexity domains and their associated patient outcomes. METHODS: An integrative literature review was conducted to identify RA-related care complexity domains and their associated patient, provider, and health system outcomes across diverse study designs. MEDLINE was searched using keywords and MeSH terms for care complexity domains and outcomes from 2000-current. Extracted data were analyzed using the constant comparison method. RESULTS: The search yielded 9835 articles, and 181 met the inclusion criteria. The care complexity domains identified included co/multimorbidity and polypharmacy, overweight/obesity, substance use, mental health, chronic pain, difficult-to-treat RA, cognitive impairment, advanced age and/or frailty, race/ethnicity, socioeconomic considerations, social support/connectedness, and healthcare access. The most common outcomes across one or more of the domains were impaired functional status, poor quality of life, elevated mortality risk, high disease activity and/or difficulty achieving remission, and higher healthcare utilization. Intersectionality between domains compounded the impact on outcomes. Evidence was unevenly distributed, with relatively few studies examining outcomes of care complexity at the health system level. CONCLUSION: We identified 12 domains of care complexity and 5 patient outcomes. Our findings will inform the development of a care complexity framework and measurement strategies to tailor care to patient needs.
Rheumatoid arthritis is a chronic systemic autoimmune disease in which the earliest breaks in immune tolerance may arise at mucosal surfaces before the clinical onset of synovitis. Among these sites, the gut has emerged as a particularly compelling candidate because it integrates microbial, epithelial, metabolic, and immune pathways with the potential to shape systemic inflammation. In this review, we examine the biological foundations of the gut–joint axis in rheumatoid arthritis, focusing on intestinal barrier structure, microbiome alterations, mucosal immune crosstalk, and mechanisms of barrier dysfunction. Current human evidence links rheumatoid arthritis to heterogeneous shifts in gut microbial composition, depletion of beneficial metabolite-producing commensals, altered immune–metabolic signaling, and biomarker patterns consistent with epithelial injury and microbial-product translocation. At the same time, available data do not support the existence of a single, universal microbial or permeability signature that defines the disease across populations. Recent longitudinal studies further challenge the concept of stable, long-standing dysbiosis and instead suggest a late, transient phase of ecological instability arising close to symptom onset. Experimental models provide stronger mechanistic support, showing that dysbiotic microbial communities, impaired barrier integrity, and strain-specific host–microbe interactions can promote T helper 17-skewed immunity and aggravate arthritis. Collectively, these findings support a context-dependent contribution of the gut to rheumatoid arthritis pathogenesis while underscoring the need for longitudinal, strain-resolved, and multi-omic human studies to clarify causality, refine disease models, and identify clinically meaningful windows for intervention.
OBJECTIVE: This study aimed to investigate the clinical and ultrasonographic factors associated with radiographic progression at 1 year after treatment initiation in patients with treatment-naïve rheumatoid arthritis (RA). METHODS: We consecutively enrolled treatment-naïve RA patients who presented to our hospital between January 2018 and December 2023. Clinical disease activity indices, musculoskeletal ultrasound (MSUS) findings of 22 joints in the hands and wrists, and radiographic findings were evaluated at baseline and at the 1-year follow-up. The data were analyzed retrospectively. RESULTS: A total of 265 patients were included. The median duration from symptom onset to treatment initiation was 3.6 months. Baseline disease activity was moderate, with mean SDAI and CDAI values of 21.2 and 19.5, respectively. All patients initiated treatment with conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and treatment was managed according to a treat-to-target strategy. At 1 year after the treatment initiation, 110 patients (41.5%) received biologic or targeted synthetic DMARDs. Concurrently, 215 patients (81.1%) maintained radiographic remission of the hands and wrists (defined as change in modified total Sharp score [Δ hand/wrist mTSS] ≤ 0.5/year). Multivariate logistic regression analysis showed significant association between clinical factors, including disease activity indices, and radiographic progression. The presence of power Doppler signals penetrating into bone erosions was the only independent factor associated with lower odds of maintained structural remission (OR 0.20; 95% CI 0.09-0.46; P < 0.001). CONCLUSION: In treatment-naïve RA patients, the presence of intra-erosive power Doppler signals on MSUS was associated with radiographic progression at 1 year after treatment initiation.
A newsletter apresenta os destaques do EULAR 2026, focando em novas evidências para o tratamento da Artrite Reumatoide e Espondiloartrite Axial. São discutidos estudos inovadores sobre o uso de tocilizumabe na depressão inflamatória, o efeito da tirzepatida no ácido úrico e a eficácia do upadacitinibe após falha terapêutica. O conteúdo também aborda o papel da IA no suporte a pacientes com esclerose sistêmica e um caso clínico de Doença de Vogt-Koyanagi-Harada.
A newsletter destaca os avanços do EULAR 2026, com ênfase no estudo INDIGO sobre o obexelimabe na doença relacionada à IgG4 e no papel do metotrexato na redução da progressão para artrite reumatoide em pacientes ACPA-negativos. Além disso, discute a importância da padronização na fisioterapia para osteoartrite e o uso combinado de biomarcadores e ultrassom para triagem de doença pulmonar intersticial.
A newsletter aborda inovações do EULAR 2026, destacando a embolização da artéria genicular como uma alternativa promissora e segura para o manejo da dor na osteoartrite de joelho refratária. O conteúdo também analisa a persistência da sarcopenia em pacientes com artrite reumatoide controlada e os desafios da inércia terapêutica no tratamento da hipertensão arterial pulmonar em pacientes com esclerose sistêmica.
Background In rheumatoid arthritis (RA), interactions between macrophages, fibroblast-like synoviocytes (FLS), and endothelial cells (ECs) drive synovial tissue (ST) inflammation and pathological angiogenesis. Preclinical models reflecting this crosstalk are needed to evaluate novel therapies. We developed a human 3D model of RA ST to assess inflammatory mechanisms and responses to small-molecule kinase inhibitors. Methods Polarized M1-like or M2-like macrophages were co-cultured with RAFLS and ECs to generate spheroids embedded in a collagen-based scaffold. Spheroids were unstimulated or exposed to pro-inflammatory stimuli, including tumor necrosis factor-α (TNF) or RA synovial fluid (SF). Treatment effects of tofacitinib (JAK1/3 inhibitor) and an IKKβ inhibitor (IKKβi; targeting NF-κB signaling) were evaluated. Readouts included spheroid outgrowth and macrophage distribution quantified by semi-automated image analysis (n = 8), cytokine production measured by ELISA/Luminex (n = 8), and RNA sequencing to identify differentially expressed genes (n = 4). Results M1-like macrophages exhibited higher core retention, while M2-like macrophages showed increased outward migration (p < 0.05). M1 spheroids demonstrated elevated expression of M1 markers, chemokines, and EC-activating signatures, whereas M2 spheroids upregulated pathways related to matrix remodeling, migration, and immunoregulation (FDR < 0.05). In M1 spheroids, TNF and SF increased macrophage core density compared with unstimulated conditions (p < 0.01) and exhibited differential effects on spheroid outgrowth. SF induced RA-associated molecular programs that were broadly suppressed by IKKβi, whereas tofacitinib selectively reduced JAK-dependent signaling (FDR < 0.05). IKKβi significantly decreased TNF-induced mediators (IL-8: p < 0.001, M-CSF: p < 0.05, SPP1: p < 0.001), and tofacitinib primarily inhibited IL-6 production (p < 0.01). Conclusions This human 3D multicellular in vitro spheroid model of synovial inflammation recapitulates key RA pathological processes and provides a robust platform for mechanistic studies
PURPOSE: In rheumatoid arthritis (RA), some patients experience joint pain that is disproportionate to the number of swollen joints, known as disproportionate articular pain (DP). This study aimed to clarify the prevalence and persistence of DP and to compare the outcomes across biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). MATERIALS AND METHODS: From the ANSWER cohort in Japan, 5489 RA patients who initiated b/tsDMARDs between January 2010 and June 2024 were screened. DP was defined as having at least seven more tender joints (TJC) than swollen joints at baseline, and 432 patients met this criterion. Persistence of DP at 3 and 6 months was evaluated. Comparative analyses were conducted across mechanisms of action (MOAs): tumour necrosis factor-α inhibitors (TNFi), cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), interleukin-6 inhibitors (IL-6i), and Janus kinase inhibitors (JAKi). RESULTS: DP was identified in 7.8% of RA patients. At 3 months, DP persisted in 40.7% (TNFi), 36.5% (CTLA4-Ig), 48.0% (IL-6i), and 54.4% (JAKi). At 6 months, corresponding rates were 43.8%, 38.7%, 49.3%, and 61.1%. Multivariate analysis showed that higher TJC and previous treatment with two or more b/tsDMARDs were associated with persistent DP, whereas higher C-reactive protein was protective. Within JAKi, baricitinib showed lower DP persistence compared with other JAKi. CONCLUSION: DP was present in approximately 8% of RA patients. Persistent DP was associated with higher TJC, greater number of previous b/tsDMARDs, and lower inflammation. No MOA was clearly superior; however, baricitinib may confer a relative benefit within the JAKi class.
Background Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease affecting synovial joints and extra-articular systems. Public recognition of early symptoms, complications, and misconceptions is important for timely help-seeking. Objective To assess public awareness of RA articular symptoms and extra-articular complications in Jordan, identify misconceptions, evaluate intended healthcare-seeking behavior, determine predictors of awareness, and examine questionnaire psychometric performance. Methods A cross-sectional online survey using nonprobability, quota-based recruitment through social media and messaging-application advertisements was conducted among adults across all Jordanian governorates between February 10 and March 24, 2026. The cleaned analytic sample included 2332 respondents. Awareness was assessed using six symptom items and five complication items, with scores transformed to a 0–100 scale. Adequate awareness was defined as correct identification of at least 6 of 11 awareness items. Misconception burden was calculated from four items. Multivariable regression identified predictors of awareness and appropriate intended action. Internal consistency and exploratory factor analysis evaluated questionnaire performance. Results The mean total awareness score was 54.4 (SD, 33.5), and 56.3% of respondents had adequate awareness. Symptom awareness was slightly higher than complication awareness (mean scores, 56.9 vs. 51.4). Joint pain (73.1%), subcutaneous nodules (68.2%), and joint deformity (64.3%) were most recognized, whereas eye inflammation (29.7%), morning stiffness (45.5%), and small-joint swelling (46.5%) were less frequently identified. Misconceptions were common: 46.7% believed RA is not serious, 34.9% endorsed herbal cure beliefs, and 30.5% confused RA with osteoarthritis. Only 40.4% selected an appropriate intended action. Prior awareness of RA, knowing someone with RA, and higher education were the strongest predictors of awareness. Symptom and complication subscales showed good internal consistency (Cronbach’s alpha, 0.806 and 0.799), and exploratory factor analysis supported a dominant general awareness factor. Conclusion
Rheumatoid arthritis (RA) is a prevalent chronic systemic autoimmune inflammatory disease that primarily targets synovial joints and periarticular tissues. In RA, systemic inflammation has been associated with extra-articular manifestations, including pulmonary involvement, which are leading causes of reduced survival. Tobacco smoking is a well-established risk factor for anti-citrullinated protein antibody (ACPA)-positive RA and is also associated with chronic obstructive pulmonary disease, interstitial lung disease (ILD) and lung cancer, the prevalence of which is elevated in people with RA. Pulmonary manifestations such as airway obstructive disease, ILD and bronchiolitis affect a substantial proportion of people with RA. Screening for pulmonary disease, particularly ILD, is gaining emphasis, with high-resolution CT recommended based on risk factors including age, sex, antibody status and smoking. Despite advances in therapies to effectively manage joint inflammation, evidence-based treatments for RA-associated ILD remain limited. Chronic obstructive pulmonary disease and bronchiectasis in RA warrant more recognition owing to their effect on morbidity and mortality, and should be managed in accordance with current international treatment guidelines for these conditions. This Review summarizes the pathophysiology of lung involvement in RA, diagnostic challenges and evolving management strategies aimed at optimizing patient outcomes.
Summary This expert position statement reframes arthroplasty and spinal fusion complications under the unified endpoint of implant fixation failure, defined as loss of mechanical integrity of the bone–implant unit over time. It synthesizes mechanistic and clinical evidence and provides evidence-informed recommendations for peri-operative bone health optimization. Background Osteoporosis is traditionally conceptualized as causing fragility fractures. However, compromised bone quality also affects the integrity of bone–implant constructs, influencing whether implants maintain fixation, interfaces remain stable, and fusion constructs consolidate. Objective To synthesize mechanistic, translational, and clinical evidence on how osteoporosis and osteoporosis pharmacotherapies influence implant fixation failure across arthroplasty and spinal fusion, and to provide evidence-informed clinical recommendations for peri-operative bone health assessment and optimization within a unified construct-level framework. Methods A position statement was developed following a structured literature search. Evidence was synthesized narratively by defining implant fixation failure as a construct-level outcome encompassing periprosthetic fracture, loosening, subsidence, pseudarthrosis, and junctional failure. Recommendations were categorized by strength (strong or conditional) and certainty of evidence (high, moderate, or low). Results Low bone mineral density (BMD) is associated with implant fixation failure across arthroplasty and spinal fusion. In arthroplasty, randomized trials demonstrate preservation of periprosthetic BMD with bisphosphonates, while registry analyses suggest improved implant survival. In spinal fusion, antiresorptive and anabolic therapies influence fixation-related parameters, with anabolic agents showing the most consistent evidence for enhanced fusion mass and earlier union. Much of the literature relies on radiographic or biomechanical endpoints rather than definitive outcomes. Conclusions Viewing arthroplasty and spinal fusion complications through a shared construct-level perspective provides a coherent link between osteoporosis and reconstructive durability. Systematic peri-operative bone health optimization may improve construct longevity, although more definitive outcome-driven trials are needed. Closer integration
Background Several cases of pyoderma gangrenosum, a rare neutrophilic dermatosis, have been reported in patients initiating biological therapies for rheumatic health conditions. Despite this, systematic analysis across available therapies is lacking. This study investigated pyoderma gangrenosum reporting in association with antirheumatic biologics to the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods Reports from FAERS (2016–second quarter of 2025) were complied, deduplicated, and standardized. Pyoderma gangrenosum cases were classified according to the Medical Dictionary for Regulatory Activities. Proportional reporting ratios (PRRs) and 95% confidence intervals (CIs) were calculated to estimate disproportionality for 20 individual antirheumatic biologics from nine pharmacologic classes. Results During the study period, 13,284,367 adverse events were reported to FAERS, including 1316 pyoderma gangrenosum cases; 868 (65.96%) cases identified an antirheumatic biologic as the primary suspect product. Positive disproportionality signals were detected for 11 study biologics belonging to six pharmacologic classes. All four interleukin (IL)-17 inhibitors exhibited disproportionate pyoderma gangrenosum reporting, with brodalumab (PRR 23.02; 95% CI 8.64–61.36) and bimekizumab (PRR 9.10; 95% CI 4.08–20.29) demonstrating the strongest signals. Positive disproportionality signals were also observed among biologics targeting tumor necrosis factor alpha, IL-6, IL-12/23, IL-23, and CD20. Similar results were obtained in sensitivity analyses. Conclusion Despite its limitations, this hypothesis-generating analysis identified significantly disproportionate pyoderma gangrenosum reporting with several antirheumatic biologics. Clinicians should remain vigilant for these paradoxical reactions in patients undergoing biologic treatment for rheumatic conditions. Key points • Pyoderma gangrenosum has been reported in patients undergoing treatment with biologics for rheumatic indications. • This study analyzed spontaneous postmarketing pyoderma gangrenosum reporting in association with 20 antirheumatic biologics. • Pyoderma gangrenosum disproportionality signals were identified for 11 biologics targeting interleukin (IL)-6, IL-17, IL-12/23, IL-23,
Objective To investigate whether lung microbial composition differs between individuals with rheumatoid arthritis and pulmonary fibrosis (RA-PF) compared to those without fibrosis (RA-no-PF). Methods We enrolled 54 RA patients (22 RA-PF, 32 RA-no-PF) from rheumatology and pulmonary clinics. PF was defined by high-resolution computed tomography (HRCT) findings. Induced sputum was analyzed using 16 S rRNA sequencing to identify the relative abundance of sputum bacteria. Taxonomic differences between groups were evaluated using three independent analytic approaches: Mann-Whitney U, DESeq2, and EdgeR, with false discovery rate correction. Logistic regression examined associations between Lautropia abundance and clinical variables. Results Individuals with RA-PF were older, more often male, and had a higher history of smoking than those with RA-no-PF. Alpha diversity was lower in RA-PF, while beta diversity did not differ between groups. Across the three analytic methods, Lautropia consistently showed decreased abundance in RA-PF compared to RA-no-PF. In multivariable models adjusting for age, sex, and smoking, RA-PF remained independently associated with undetectable levels of Lautropia (OR = 0.14, p = 0.023). Within RA-PF, when Lautropia was undetectable, there was no difference in pulmonary physiology but did show a trend towards more lung fibrosis. Conclusion Sputum Lautropia is significantly reduced in RA-PF, and its absence may correlate with more severe fibrosis. These findings support a potential role for the lung microbiome in the pathogenesis of pulmonary fibrosis and raise the possibility that commensal taxa such as Lautropia modulate fibrotic pathways. Longitudinal and mechanistic studies are needed to determine whether Lautropia depletion precedes fibrosis and whether microbial-directed approaches represent new therapeutic avenues in RA.
OBJECTIVE: To compare frailty prevalence and factors driving frailty between older adults with rheumatoid arthritis (RA) and controls, using two conceptually distinct frailty instruments. METHODS: Cross-sectional data from the STudying Ageing in Rheumatoid arthritis (STAR) study were used, including 207 patients with RA and 214 population controls aged 55-85 years. Frailty was assessed using the Groningen Frailty Indicator (GFI; 15 yes/no items; physical, cognitive, social, psychological domains; frail≥4/15) in all participants and the Fried criteria (5 yes/no items; physical domain; prefrail=1-2, frail≥3, and combined frail/prefrail≥1 deficit) in a clinically assessed subgroup (RA: n = 88, controls: n = 96). Prevalence and overlap between instruments were described by group. Uni- and multivariable logistic (GFI: frailty vs. robust) and Poisson (Fried: frail/prefrail vs. robust) regressions assessed effects of age, group, the age*group interaction, and additional covariates. RESULTS: Frailty prevalence was higher in RA than controls for GFI-frailty (34% vs 18%) and Fried-frailty/prefrailty (72% vs 50%). Among GFI-frail persons, 88% of patients with RA compared to 69% of controls were also frail or prefrail by Fried. Age was not associated with frailty in uni- or multivariable analyses for either instrument, in RA or controls (p interaction age*group>0.10). The association with RA became insignificant after multivariable adjustment. Living alone, comorbidity score ≥1, higher fatigue, and anxiety were associated with GFI-frailty, and higher BMI and poorer physical function with Fried- frailty/prefrailty. CONCLUSION: Older adults with RA show higher (pre)frailty prevalence than controls, which is associated with disease-related consequences and vulnerability rather than age, questioning the added value of frailty assessment beyond routine clinical evaluation.
Background The expanding use of biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) has substantially improved outcomes in autoimmune diseases but is accompanied by complex safety concerns. Risk management plans (RMPs) have been introduced to mitigate treatment-related risks; however, real-world adherence to these strategies and their broader clinical impact remain incompletely characterized. Methods We conducted a retrospective observational cohort study of adult patients with autoimmune diseases who received bDMARDs, tsDMARDs, or biosimilars at a tertiary medical center in southern Taiwan between October 2014 and December 2023. Patients were classified into RMP and non-RMP groups based on completion of predefined pre-treatment safety assessments within 6 months prior to therapy initiation, including pulmonary and tuberculosis evaluation, viral hepatitis screening, and documentation of cardiovascular and malignancy risk factors. Clinical outcomes included Pneumocystis jirovecii pneumonia (PJP), major adverse cardiovascular events (MACE), treatment-related respiratory adverse events, and all-cause mortality. Multivariable logistic regression and time-to-event analyses were performed to evaluate associations between RMP implementation and clinical outcomes. Results Among 1,078 patients included, only 348 (32.3%) fulfilled the predefined RMP criteria prior to treatment initiation. Compared with the RMP group, patients without RMP exhibited significantly higher incidences of PJP (11.9% vs. 2.3%), MACE (8.5% vs. 2.6%), treatment-related respiratory adverse events (50.4% vs. 42.8%), and all-cause mortality (7.3% vs. 1.7%) (all p < 0.05). After multivariable adjustment, RMP implementation remained independently associated with lower risks of PJP (adjusted odds ratio [aOR] 0.18, 95% CI 0.15–0.84), MACE (aOR 0.30, 95% CI 0.13–0.71), and all-cause mortality (aOR 0.21, 95% CI 0.07–0.61). Subgroup and time-to-event analyses demonstrated that anti-CD20 therapy was associated with the highest risk of early-onset PJP, MACE, and mortality, with most events occurring within the first three
Objectives To describe imaging features of 18F-FDG positron emission tomography/computed tomography (PET/CT) of polymyalgia rheumatica (PMR) and evaluate their ability to distinguish PMR in elderly patients presenting with myalgia. Methods Ninety-three elderly patients (male 29, female 64, age 66.3 ± 8.7 years) with myalgia underwent 18F-FDG PET/CT for suspected PMR. Based on final clinical diagnosis, clinical data of PMR patients and other subjects were compared. Diagnostic efficacy of 2012 EULAR/ACR classification criteria was assessed. PET/CT findings were reviewed to define PMR-related metabolic patterns. An imaging score algorithm was developed to discriminate PMR from rheumatoid arthritis (RA), the most common alternative diagnosis. The score algorithm’s diagnostic performance was validated in the cohort. Results Based on final clinical diagnosis, 44 (47.3%) patients were PMR and 49 (52.7%) were other rheumatic disorders. PMR often presented with fever and hip pain and was absent of other joint involvement. The EULAR/ACR classification criteria reached a maximum accuracy of 55.3%. PET/CT consistently demonstrated PMR-related uptake in the interspinous bursae, pubic tendon entheses, and ischial tuberosity bursae; some patients showed giant-cell arteritis (GCA) through abnormal vascular uptake. An 8-item PET/CT score (1 point per criterion) of ≥ 4 distinguished PMR from RA, with 95.5% sensitivity, 85.2% specificity, and 91.5% accuracy. For the entire cohort, a score ≥ 5 achieved 84.1% sensitivity, 94.8% specificity, and 88.2% accuracy. Conclusion 18F-FDG PET/CT outperformed the EULAR/ACR criteria for early and accurate diagnosis of PMR in elderly individuals with myalgia. Key Points • FDG PET/CT assists in the diagnosis of PMR. • FDG PET/CT achieves higher diagnostic accuracy for PMR than the 2012 EULAR/ACR criteria. • Eight-item PET/CT score distinguishes PMR from RA with 91.5 % accuracy in elderly myalgia.
Outcomes in rheumatoid arthritis (RA) have improved considerably with the advent of new therapeutic modalities, improved therapeutic strategies and greater recognition of the need to manage comorbidities. Nevertheless, unmet needs remain. Sustained remission is achieved by only a minority of patients, in part owing to delays in diagnosis, imprecise risk stratification and suboptimal treatment selection. A pressing need therefore exists for robust diagnostic and prognostic tools to support clinical decision making. Advances in genetic, protein, imaging and multi-omics biomarkers offer opportunities to refine RA diagnosis, predict disease course and guide therapeutic choices. Parallel progress in biomarker discovery is also shaping understanding of major RA-associated comorbidities, including cardiovascular disease, interstitial lung disease, osteoporosis and malignancy. Together, clinical introduction of such biomarkers could enable earlier intervention, more precise therapy and improved outcomes for patients with RA.
Introduction Limited access to biologic disease-modifying antirheumatic drugs (bDMARDs) in resource-constrained settings influences treatment sequencing after failure of conventional synthetic DMARDs (csDMARDs). Evidence regarding upfront use of low-dose rituximab as first biologic therapy remains limited. This study aimed to evaluate the effectiveness and steroid-sparing potential of upfront low-dose biosimilar rituximab in biologic-naïve patients with seropositive rheumatoid arthritis refractory to maximally tolerated triple csDMARD therapy. Methods This prospective single-centre observational study included biologic-naïve anti-CCP-positive rheumatoid arthritis patients with inadequate response to ≥ 6 months of methotrexate, hydroxychloroquine, and sulfasalazine. Patients received two infusions of biosimilar rituximab (500 mg each) administered 2 weeks apart while continuing background csDMARDs. Disease activity was assessed using DAS28-ESR at baseline and weeks 2, 6, 12, and 24. Longitudinal changes were analyzed using Friedman and Wilcoxon signed-rank tests. Results Seventy-five patients (88% women) were included. Mean DAS28-ESR decreased from 5.57 at baseline to 2.78 at week 24 (p < 0.001), with a median reduction of 2.7 points. Remission rates increased from 0% to 50.7% at 24 weeks. Mean tender joint count declined from 9.43 to 1.33 and swollen joint count from 4.43 to 0.37. All patients discontinued corticosteroids during follow-up. Infusion reactions were mild, and no mortality occurred. Conclusions Upfront low-dose biosimilar rituximab as first biologic therapy achieved significant and sustained disease activity reduction with high remission rates and successful steroid withdrawal, supporting a rituximab-first strategy in resource-limited public health settings. Key Points • Upfront low-dose biosimilar rituximab (500 mg × 2) significantly reduced disease activity in biologic-naïve, seropositive rheumatoid arthritis after triple csDMARD failure. • Mean DAS28-ESR decreased from 5.57 to 2.78 at 24 weeks, with 50.7% of patients achieving remission. • All patients discontinued corticosteroids, and 50% discontinued both sulfasalazine and
Glucocorticoid treatment for patients with rheumatoid arthritis (RA) is widely used as fast-acting bridging therapy to reduce disease activity. However, the safety is still discussed. This cohort study describes glucocorticoid dosage during the first year after treatment initiation in patients with RA and secondarily presents the one-year dosedependent infection risk. Hospital records were reviewed for 574 newly diagnosed RA cases treated at Department of Rheumatology Aalborg University Hospital between 2014 and 2022 to identify physician prescribed daily glucocorticoid dose and infections within the year following first visit. Daily glucocorticoid dose was presented. Secondary, the relative risk (RR) for one-year dose-dependent (non-exposed, low dose: 0-10 mg/day, high dose: >10 mg/day, from 21 days average) risk of first infection was calculated using modified Poisson regression. In total, 428 patients (75%) received glucocorticoid during the first year, with 313 (55%) initiated at first visit. Mean prescribed glucocorticoid dose was 9.3 mg/day, with 262 patients (46%) receiving tablets and 270 (47%) receiving intra-articular injection. Overall, 117 patients (20%) experienced an infection within the first year. The model was adjusted for asthma/chronic obstructive pulmonary disease, sex, and age, yielding a RR of 1.13 (95% confidence interval (CI): 0.77 to 1.67) for low-dose exposure versus non-exposure. Glucocorticoid dosages were highest early in disease course and declined substantially after the initial visit, suggesting that physicians in the Danish healthcare decrease dose within the first year after diagnosis. CI for dose-dependent infections risk were compatible with both benefit and harm.
A newsletter apresenta os principais destaques do congresso EULAR 2026, abordando desde a eficácia da manutenção do alopurinol na gota até novos alvos terapêuticos para a Síndrome de Sjögren. Além das atualizações clínicas, explora como fatores psicossociais e a satisfação conjugal influenciam diretamente o prognóstico e a saúde mental de pacientes com doenças reumáticas crônicas.
The biomarker potential of CD4+T cell subsets (naive, regulatory (Treg), inflammation-related cells (IRC)) in patients with rheumatoid arthritis (RA) has been described. OBJECTIVE: This article investigates the dynamic changes in these biomarkers across the RA disease continuum from at-risk to drug-induced remission. METHODS: T cell subset biomarker data were acquired using flow cytometry. Multiple group comparison were performed using ANOVA test (with Bonferroni correction). RESULTS: In individuals at-risk of RA, longitudinal analysis showed that IRC frequencies increased just prior to onset of clinical synovitis, while naïve T cell frequencies reduced in those progressing to clinical synovitis, but increased in non-progressors. The use of naïve/IRC data improved the accuracy of RA classification, especially in ACPA-negative patients. A distinct T cell biomarker signature was observed in late-onset RA (>60 years old vs <59). In untreated RA, the predictive value of naïve T cell frequencies for methotrexate response was confirmed. For patients on methotrexate, naïve T cells increased only between 6-12 months and only when in remission. IRC and Treg showed no consistent change. In patients treated with TNF inhibitors, naïve T cell frequency increased independently of response, whilst sustained IRC reductions and Treg increases were seen in remission. Once in stable clinical remission, only naive frequencies increased with the length of remission on conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), whilst only Treg increased over time in TNF inhibitor-induced remission. CONCLUSION: These studies validated that T cell subset measurements are independent from other currently used biomarkers, highlighting differences in the impact of drug modes of action on the three T cell subsets. There is still an unmet need for biomarkers to predict response to TNF-inhibition in early RA.
PURPOSE OF REVIEW: People with Down syndrome experience significant immune dysregulation, conferring elevated risk of autoimmune and inflammatory conditions. Despite the growing prevalence of adults living with Down syndrome, significant gaps remain in understanding and treating immune-mediated disease in this population. This review synthesizes current knowledge of immune dysregulation in Down syndrome, with focus on rheumatic manifestations and emerging therapeutic approaches. RECENT FINDINGS: Trisomy 21 drives constitutive, global immune remodeling characterized by mixed interferon hyperactivation, hypercytokinemia, and myeloid and lymphoid subset remodeling toward an autoimmunity-prone, pro-inflammatory state. Down syndrome associated arthritis is a distinct and aggressive entity warranting recognition separate from juvenile idiopathic and rheumatoid arthritis. People with Down syndrome face elevated risk of SJIA-associated lung disease and diffuse alveolar hemorrhage. Medication tolerance is a significant consideration, including intolerance to methotrexate and diminished response to TNF inhibitors. Early clinical trials of JAK inhibitors demonstrate promising results across multiple immune-mediated manifestations, including skin disease, arthritis, and Down syndrome regression disorder. SUMMARY: Immune dysregulation in Down syndrome is pervasive and mechanistically distinct, with interferon signaling as a central therapeutic target. Clinicians should be aware of Down syndrome specific diagnostic and management considerations, and future research should prioritize rigorous placebo-controlled trials and Down syndrome informed outcome measures.
Background Rheumatoid arthritis (RA) is a significant global health issue. Early diagnosis remains clinically challenging, particularly in patients with inflammatory arthritis who do not yet fulfill 2010 ACR/EULAR classification criteria (undifferentiated arthritis, UA). Methods This retrospective study enrolled 83 treatment-experienced RA (TE-RA), 49 treatment-naïve RA (TN-RA), and 51 seropositive UA patients, as well as 60 healthy controls. Peripheral lymphocyte subsets and serum cytokines were profiled using flow cytometry and bead arrays. Least absolute shrinkage and selection operator (LASSO) regression was utilized to develop an immune-based derivation-stage classifier for distinguishing TN-RA from UA, with internal validation by bootstrap resampling (B = 1000). Results Immunophenotypic analysis identified distinct immune profiles between TN-RA and UA at initial presentation. TN-RA was characterized by IL-2 signaling exhaustion (elevated sIL-2R, decreased IL-2), systemic inflammation (elevated IL-6, IFN-γ, and TNF-α), and compensatory memory Treg expansion (increased CD45RO+ Tregs). In contrast, UA exhibited a Th17/Treg imbalance with relatively preserved Th2 and Th17 responses. An eight-feature immune signature (sIL-2R, IL-6, CD45RO+ Tregs, CD45RO+ Treg%, IFN-γ, Th17/Treg ratio, Th2, Th17%) discriminated TN-RA from UA with an optimism-corrected AUC of 0.959 (95% CI: 0.923–0.995), adjusted for age, sex, BMI, and disease duration. sIL-2R and IL-6 were the strongest contributors, consistent with their central roles in RA pathophysiology. Conclusions In the present study, an immune-based derivation-stage classifier showed potential for distinguishing TN-RA from UA at initial presentation. The IL-2-Treg axis perturbation represents a potential pathophysiological distinction, with sIL-2R as a candidate biomarker. These findings suggest that objective immune profiling may inform clinical decision-making when conventional criteria are inconclusive.
Objective Individuals with systemic autoimmune rheumatic diseases (SARDs) are at risk for worse acute and post–acute COVID‐19 outcomes, though whether individuals with SARDs have longer persistence of viral antigens after COVID‐19 has not been studied. Methods This retrospective cohort study evaluated post–COVID‐19 differences in SARS‐CoV‐2 antigen (spike, spike protein that contains the receptor‐binding domain, and nucleocapsid) positivity between individuals with SARDs (COVID‐19 and Rheumatic Diseases [RheumCARD]) and without SARDs (Researching COVID to Enhance Recovery [RECOVER]–Adult). SARS‐CoV‐2 antigens were measured in collected samples using a validated ultrasensitive single molecule array. This digital enzyme‐linked immunosorbent assay used antibody‐coated magnetic beads to capture antigen molecules, which were loaded into microwell arrays and detected through enzymatic cleavage of a fluorescent substrate. We used logistic regression to estimate unadjusted and adjusted (for age, sex, infection year, vaccination status, and COVID‐19 treatment) odds ratios for SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19. Results Among 210 individuals with SARDs in RheumCARD and 348 individuals without SARDs in RECOVER‐Adult, any SARS‐CoV‐2 antigen positivity was more common in those with SARDs (36.7% in RheumCARD vs 18.9% in RECOVER‐Adult; P < 0.001). Those with SARDs had higher odds of nucleocapsid antigen positivity (adjusted odds ratio [aOR] 3.73, 95% confidence interval [CI] 1.28–10.85) or any antigen positivity (aOR 2.89, 95% CI 1.43–5.85) three months after COVID‐19 infection and higher odds of nucleocapsid antigen positivity (aOR 6.62, 95% CI 1.09–40.30) six months after COVID‐19 infection. Conclusion Individuals with SARDs were more likely to have SARS‐CoV‐2 antigen positivity at months 3 and 6 following COVID‐19 infection compared with individuals without SARDs, not explained by demographics, variant, vaccination, or treatment.
Objective Monitoring rheumatoid arthritis (RA) disease activity is crucial for treatment optimization. Hematological indices (SII, SIRI, NLR, PLR, MLR) show promise as systemic inflammation biomarkers. This study assessed their correlation with RA disease activity versus healthy controls. Methods This retrospective cross-sectional study included 204 ACR/EULAR-classified RA patients and 216 age-/sex-matched controls. Complete blood counts enabled calculation of SII (neutrophils × platelets/lymphocytes), SIRI (neutrophils × monocytes/lymphocytes), NLR, PLR, and MLR. Disease activity was measured via DAS-28-ESR. Results RA patients (96.2% female, age 50.9 ± 12.4 years) demonstrated significantly elevated indices versus controls (94.4% female, age 47.2 ± 11.9 years): SII (722.7 ± 695.2 vs. 563.1 ± 448.9; p = 0.006), SIRI (12.36 ± 9.46 vs. 10.32 ± 5.78; p = 0.009), PLR (12.10 ± 14.40 vs. 9.64 ± 9.67; p = 0.039), MLR (0.21 ± 0.19 vs. 0.17 ± 0.08; p = 0.015). Among RA patients, active disease (DAS-28 > 2.6) exhibited significantly higher SII (780.6 ± 826.1 vs. 614.4 ± 310.4; p = 0.040) than remission. ROC analysis identified SII/SIRI as strong predictors (AUC train/test: 0.946/0.898). Conclusion Hematological indices were significantly higher in RA patients and associated with disease activity. SII and SIRI demonstrated superior predictive capability for active RA. Key Points • This retrospective cross-sectional study included 204 patients with rheumatoid arthritis and 216 age- and sex-matched healthy controls. • Hematological indices including SII, SIRI, NLR, PLR, and MLR were significantly higher in RA patients compared to controls. • Among these indices, SII and SIRI showed the strongest correlation with disease activity measured by DAS-28. • SII and SIRI demonstrated excellent predictive performance for distinguishing active disease from remission, suggesting their potential as simple and cost-effective biomarkers for clinical monitoring.
Introduction Folic acid is routinely co-administered with methotrexate (MTX) to reduce toxicity; however, the optimal dose remains unclear. This study investigated whether increasing the weekly folic acid dose from 5 to 10 mg reduces MTX-related toxicity in patients receiving stable-dose MTX therapy. Methods In this single-center, open-label, randomized controlled trial, 44 patients with rheumatic diseases on stable-dose MTX either received 10 mg (ARM-1) or 5 mg (ARM-2) of folic acid per week for 12 weeks. Liver damage, other MTX-related toxicities, and erythrocyte MTX-polyglutamate (MTX-PG) concentrations were compared between groups using logistic regression analysis or analysis of covariance. Japan Registry of Clinical Trials (number: jRCT1061230085). Results Forty-two patients completed the study. The presence of liver damage at Day 84 did not differ significantly between the two groups (OR 0.41, 95% CI, 0.01–5.75, p = 0.506). Adjusted mean differences in aspartate transaminase and alanine transaminase at Day 84 between the groups were − 0.33 U/L (95% CI, − 2.68 to 2.02; p = 0.779) and − 0.44 U/L (95% CI, − 5.39 to 4.51; p = 0.859). Comparison of outcomes between groups at Day 84 showed no significant differences in any outcomes, except for fatigue severity (adjusted mean difference, − 0.87; 95% CI, − 1.71 to − 0.04; p = 0.041). Baseline fatigue was associated with baseline MTX-PG2 or MTX-PG1-2 concentrations (OR, 1.06; p = 0.049 or OR, 1.03; p = 0.040, respectively). Conclusions Increasing folic acid dose to 10 mg/week showed little effect on reducing MTX-related toxicity, although it may improve fatigue in selected patients. Key Points • Increasing the weekly folic acid dose from 5 mg to 10 mg showed no additional benefit in reducing methotrexate-related toxicity in patients on stable-dose MTX. • Higher-dose folic acid was
Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Efferocytosis is a critical immune process through which the body clears apoptotic cells. Its dysfunction is closely associated with the development of various autoimmune diseases, but its mechanism in RA remains unclear. This study aims to systematically screen candidate biomarkers based on efferocytosis-related genes (ERGs) in RA by integrating bioinformatics and machine learning approaches, and to conduct preliminary validation at both cellular and clinical levels. Methods The GSE55235 and GSE77298 data sets were retrieved from the GEO Database, which were regarded as the training set after merging and batch effect correction. The GSE55457 and GSE12021 data sets were used as the independent validation sets. By intersecting ERGs with differentially expressed genes (DEGs) in RA and control groups, differentially expressed ERGs (DE-ERGs) were identified for further study. Three machine learning algorithms, LASSO, Random Forest, and SVM-RFE, were employed to determine hub genes and evaluate their ability to distinguish RA. The ssGSEA algorithm was utilized to study immune cell infiltration in RA. Additionally, transcription factors (TFs) and miRNAs of hub genes were predicted. qRT-PCR and ELISA were used to validate the expression of key genes in clinical blood samples, and functional experiments were conducted in synovial fibroblasts to explore their biological roles. Results Three hub genes (PTPN6, CASP1, and CD47) were identified through LASSO, RF, and SVM-RFE algorithms. Hub genes exhibited good distinguishing capability in both the training and validation sets. In addition, immune infiltration analysis demonstrated greatly higher infiltration of immune cells such as B cells, CD8 + T cells, macrophages, DCs, NK cells, and Tregs in the RA group than in the control group.
Objective To evaluate real-world treatment maintenance, effectiveness, and safety of Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA), and to assess changes in prescribing patterns following the October 2022 PRAC recommendations. Methods This retrospective single-center study included all consecutive RA patients initiating a first JAKi (tofacitinib, baricitinib, upadacitinib, or filgotinib) between April 2018 and November 2023. The primary endpoint was treatment maintenance (Kaplan–Meier). Secondary outcomes included changes in DAS28-CRP and DAS28 at 6 and 12 months and reasons for treatment discontinuation. Patients initiating JAKi before versus after PRAC were compared. Results Among 120 patients (85% women, mean age 57 ± 14 years, mean disease duration 19 ± 12 years, mean follow-up of 21 ± 16 months), overall treatment maintenance was 73% at 12 months, 62% at 24 months, and 57% at 36 months. Baricitinib showed the highest long-term persistence, whereas filgotinib demonstrated excellent 12-month survival in younger, low-risk patients. All JAKi significantly improved disease activity, with reductions in DAS28-CRP of –1.57 ± 1.26 at 6 months and –1.13 ± 1.63 at 12 months. Forty-nine discontinuations occurred (57% inefficacy, 35% intolerance) after a mean follow-up of 15 ± 15 months. Serious adverse events included three pulmonary embolisms and one myocardial infarction, all in high-risk patients before PRAC. No major cardiovascular events, venous thromboembolism, or malignancies occurred after PRAC recommendations. Conclusion JAKi demonstrated effectiveness and acceptable long-term persistence. Safety outcomes were strongly influenced by baseline cardiovascular risk, underscoring the need for careful patient selection following PRAC guidance. Key Points • In routine care, all four JAK inhibitors demonstrated clinically meaningful effectiveness despite long-standing, severe and comorbid rheumatoid arthritis. • Treatment persistence differed across JAK inhibitors, but observed differences were largely driven by patient profiles and prescribing context rather than clear drug-related effects.
A newsletter apresenta os resultados do estudo REPLENISH, que valida o secuquinumabe como uma nova opção biológica para a polimialgia reumática, dobrando as taxas de remissão sustentada. São discutidos também novos insights do EULAR 2026, incluindo a distinção entre entesófitos inflamatórios e mecânicos, o valor prognóstico do fator reumatoide na GEPA e o potencial das fibras dietéticas em melhorar a resposta clínica ao metotrexato na artrite reumatoide.
Rheumatoid arthritis (RA) is associated with a wide spectrum of comorbidities that substantially influence quality of life and long-term outcomes. These include extra-articular manifestations, cardiovascular disease, cerebrovascular accidents, dementia, malignancy, infection, mental health disorders and osteoporosis. Patterns of comorbidity in RA have evolved over the past three decades, with declining prevalence of some complications alongside persistently high or increasing burdens of interstitial lung disease, anxiety and depression. Shifts in the comorbidity landscape probably reflect advances in RA management, including the expanded use of biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) and a widespread adoption of treat-to-target strategies. Consideration of comorbidity-specific epidemiology, the potential effect of DMARDs on comorbidity risk and opportunities to address both RA and comorbid disease are increasingly relevant in clinical care. Preventive strategies, including selected enhanced screening approaches such as those for cervical cancer, interstitial lung disease, cardiovascular disease and osteoporosis, form an important component of comprehensive RA management. Awareness of the changing comorbidity landscape could support more integrated and individualized care for people with RA.
A newsletter destaca os resultados do estudo de fase 3 VALOR, que comprovou a eficácia do brepocitinibe na melhora cutânea e muscular da dermatomiosite, permitindo o desmame de corticoides. São discutidas também inovações como o uso de blinatumomabe para restaurar a responsividade terapêutica na artrite reumatoide e a aplicação de células CAR-T em casos refratários, além de novos escores para estratificação de risco gestacional.
Objective To identify autoantibodies in presymptomatic individuals that associate with the onset of rheumatoid arthritis (RA) and to distinguish early RA from osteoarthritis (OA), particularly in individuals lacking classic RA serologic markers. Methods We analyzed serum and plasma from three cohorts: presymptomatic individuals who later developed RA (n = 518), a subset of these at RA diagnosis (n = 241), matched population controls (n = 530), and patients with OA (n = 287). Bead‐based multiplex flow immunoassay detected IgG autoantibodies against joint‐related peptides relevant in arthritis models. Principal component analysis was used to identify subgroups and univariable regression analyses to characterize the performance of autoantibodies with significance for patients with RA negative for anti–cyclic citrullinated peptide (anti‐CCP) and rheumatoid factor (RF), that is, the seronegative RA diagnosis (SeNe) test. Multivariable logistic regression identified autoantibodies with the strongest discriminative power between cases and controls. Results Autoantibody profiles revealed three distinct presymptomatic subgroups, suggesting early immune heterogeneity. The SeNe test was associated with symptom onset within 2.5 years in 13% of anti‐CCP and RF‐negative individuals. Specificity for RA versus OA was 97% (95% confidence interval, 95%–99%). An improved version (SeNe 2.0) identified 16% of anti‐CCP and RF‐negative presymptomatic individuals with 98% specificity versus population controls. Two of five SeNe 2.0 autoantibodies were associated with the presymptomatic state in the multivariable model, including RF and anti‐CCP. Conclusion These novel biomarkers can identify presymptomatic, seronegative individuals at high risk of RA onset and support their recruitment into trials for personalized prevention. Additionally, they distinguish early seronegative RA from OA with high specificity. image
Objective The presence of anti–citrullinated protein antibodies in the absence of clinical inflammatory arthritis identifies individuals at risk for rheumatoid arthritis (RA). We examined whether epigenetic remodeling of DNA methylation distinguishes those who ultimately develop RA (“converters”) from individuals who remain asymptomatic (“nonconverters”). Methods Genome‐wide DNA methylation was quantified in peripheral blood mononuclear cells separated into CD4 T memory and naive cells and B cells collected at baseline and longitudinally over up to five years from converters who were anti‐CCP3 positive (n = 21), nonconverters who were anti‐CCP3 positive (n = 50), and controls who were anti‐CCP3 negative (n = 69), as well as patients with early RA (n = 29). Differentially methylated loci (DMLs) were identified, followed by pathway enrichment analysis. Machine‐learning algorithms assessed the predictive value of individual CpG sites for future RA onset. Results At baseline, DMLs clearly separated converters from nonconverters and patients with early RA. Among the pathways associated with differentially methylated genes, enrichment of aberrant NOTCH signaling and DNA repair pathways was particularly prominent in B cells. Longitudinally, methylomes remained stable in controls and nonconverters but underwent progressive remodeling in converters, tracing a “RA methylome trajectory” toward the early RA methylome involving regulatory elements. Machine‐learning models incorporating top CpG predictors accurately classified future converters with RA. Conclusion DNA methylation is a dynamic process that continuously remodels in individuals who were asymptomatic and anti‐CCP3 positive as they progress to disease, whereas it remained relatively stable in nonconverters and controls. Progressive epigenetic remodeling during the trajectory from at risk to clinical arthritis highlights pathogenic pathways and yields biomarkers that may inform prognostic testing and preventive intervention in preclinical RA.
Background Although effectively controlling inflammation, up to 50% of patients with rheumatoid arthritis (RA) experience persistent pain, associated with central sensitization and neuroinflammation. Home-based transcranial direct current stimulation (tDCS) has shown efficacy in chronic pain. Objective To investigate whether anodal tDCS (a-tDCS) is more effective than sham stimulation in reducing pain. Methods Randomized, double-blind, sham-controlled trial with 34 women (18–70 years) with RA and VAS > 40 mm. Participants were randomized to receive a-tDCS (n = 17) or sham tDCS (n = 17). Home-based tDCS (2 mA, 20 min/day) or sham (2 mA, 90 s) for four weeks, using anodal-left M1 montage. Primary outcomes was pain (Visual Analogue Scale, VAS), Secondary outcomes included pressure pain threshold (PPT), central sensitization (CSI), physical function (HAQ-DI), fatigue (FACIT-F), CNS biomarkers, adherence, and safety. Results Mean VAS reduction from baseline was greater in the a-tDCS group (-33.5 mm) versus s-tDCS (-14.1 mm), with a between-group difference of -19.4 mm (95% CI, -29.3 to -9.5; p = 0.003). Linear mixed-effects models showed that a-tDCS reduced VAS pain by 27.7% versus 6.0% with sham, a between-group difference of 21.7% (Cohen’s d = 1.15). HAQ-DI improved by 38.0% versus 7.2% (ES = 1.10). a-tDCS reduced analgesic use by 62% (RR = 0.38; 95% CI, 0.18–0.79). Exploratory analyses suggested that neuroplasticity mechanisms might mediate these effects. Conclusion Home-based a-tDCS effectively reduced pain, disability, and analgesic use in RA patients with persistent pain without objective inflammation.
Innate lymphoid cells (ILCs) are emerging as critical modulators of inflammation in rheumatoid arthritis, contributing to both disease pathology and resolution. Group 3 ILCs (ILC3s) mirror TH17 cells in their production of IL-17A and IL-22, promoting fibroblast activation, neutrophil recruitment and synovial inflammatory cascades. By contrast, group 2 ILCs (ILC2s) engage reparative and immunoregulatory pathways via secretion of IL-9, IL-13 and IL-10. Lymphoid tissue inducer (LTi) ILCs contribute to ectopic lymphoid tissue neogenesis and stromal remodelling in early disease. Clinically, alterations in ILC subset composition correlate with disease activity, therapeutic responsiveness and inflammatory burden. Advances in high-dimensional immunophenotyping, spatial transcriptomics and single-cell multi-omics now enable precise mapping of ILC subsets and their effector programmes across peripheral blood and synovial tissue, supporting their use in biomarker discovery and treatment pipelines. Furthermore, modulation of ILCs by targeting upstream cytokines, signalling pathways or the use of microbiota-derived metabolites is a potential therapeutic strategy. Finally, cell-based avenues include IL-10-producing ILC2s (ILC210) and engineered chimeric antigen receptor (CAR)-ILC2s for targeted, tissue-resident immune modulation. Although still in the preclinical stages, these approaches highlight the translational potential of ILCs as biomarkers and therapeutic targets in rheumatoid arthritis.
A newsletter discute os desafios práticos e emocionais da maternidade em mulheres com doenças reumáticas, destacando que o cuidado médico deve transcender métricas clínicas como o DAS-28. Além disso, apresenta atualizações científicas sobre novos biomarcadores de inflamação coronariana na artrite reumatoide e a caracterização de fenótipos específicos em pacientes com anticorpos anti-CENP-B e anti-SSA.
Sex and gender shape disease presentation, diagnostic accuracy, treatment response and clinical outcomes in rheumatology, yet these dimensions remain insufficiently embedded in clinical practice. Owing to the markedly unbalanced sex prevalence ratios across many rheumatic diseases, the ‘minority’ sex is consistently under-represented in clinical studies, limiting the interpretation of long-term outcomes and treatment effectiveness. Sex-related differences in pain perception, inflammatory biomarkers and imaging patterns further complicate disease assessment, and treatment allocation and drug persistence also differ between women and men. Gender-related factors — including disparities in care-seeking behaviours, social roles and lifestyle factors — additionally modulate symptom burden and disease trajectories. Evidence remains particularly scarce for transgender, gender-diverse and intersex individuals, who are rarely captured in clinical cohorts, restricting the development of inclusive and generalizable evidence. Embedding sex-aware and gender-aware approaches into diagnostic reasoning, risk assessment and therapeutic decision-making is therefore essential for advancing precision, equity and truly personalized rheumatological care. Such integration enables clinicians to interpret disease signals more accurately, anticipate divergent multimorbidity trajectories and tailor treatment strategies to the biological and sociocultural contexts of each patient.
OBJECTIVE: While osteoarthritis (OA) and rheumatoid arthritis (RA) can necessitate total knee arthroplasty (TKA), the mechanisms and radiographic patterns of joint space narrowing (JSN) differ. Deep learning (DL) enables compartment-specific measurement of minimum joint space width (mJSW). This study compared JSN patterns between patients with RA and OA undergoing TKA and evaluated associations between mJSW and RA disease activity. METHODS: In this retrospective study, 409 RA patients undergoing TKA (2000-2021) were age- and sex-matched with OA patients. A validated DL model quantified medial and lateral mJSW from AP knee radiographs at two time points: early (>2 years before TKA) and late (≤2 years before TKA). The rate of JSN was calculated in 302 patients with paired radiographs. Mixed-effects models adjusted for BMI and alignment. RA disease activity, serology, and medications were recorded. RESULTS: RA demonstrated narrower lateral mJSW than OA at the late time point (5.6 vs. 7.0 mm, P<0.01), with comparable medial values. RA exhibited uniform bicompartmental JSN, whereas OA patients showed medial narrowing. RA had a faster mean lateral ΔmJSW (0.11 mm/year; P = 0.01), while OA had a faster mean medial ΔmJSW (0.21 mm/year; P<0.001). Longer RA duration and higher inflammatory markers were negatively associated with lateral mJSW. Seronegative RA showed faster lateral ΔmJSW in the surgical knee than seropositive patients (0.12 vs 0.06 mm/year; P = 0.03). CONCLUSION: Patients with RA demonstrated diffuse, symmetric cartilage loss contrasting with medialpredominant narrowing in patients with OA. Automated DL-based measurement enables scalable, compartment-specific assessment of compartment-specific patterns of joint degeneration.
A newsletter destaca que a prednisolona adjuvante não reduziu lesões coronarianas na Doença de Kawasaki, embora tenha diminuído a necessidade de terapia de resgate. Além disso, discute como o dano histológico crônico é o principal preditor de perda renal no lúpus e o aumento significativo de flares de artrite reumatoide no período pós-parto.
A newsletter destaca que a hidroxicloroquina não previne a progressão para artrite reumatoide em pacientes anti-CCP positivos e que a plasmaférese deve ser reservada como terapia de resgate em miosites graves. Além disso, discute o benefício do AAS na redução de eventos isquêmicos na arterite de células gigantes, apesar do aumento do risco hemorrágico, e explora a relação entre tofacitinibe e microbiota na espondiloartrite.
A newsletter destaca o benefício clínico do TENS na fibromialgia e a utilidade do ultrassom pulmonar como ferramenta portátil para monitorar a progressão da doença intersticial na artrite reumatoide. Também são discutidos a correlação entre o local das crises de reumatismo palindrômico e a cronificação articular, além do papel da disbiose oral na Síndrome de Sjögren.
Objective This study aimed to assess the prevalence of comorbidities among patients with rheumatoid arthritis (RA) and identify factors associated with it. Methods A cross-sectional study was conducted at 2 tertiary care hospitals among 653 patients with RA. Data on demographics, poor prognostic factors (high erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], rheumatoid factor, anticyclic citrullinated peptide antibody titers, and Disease Activity Score in 28 joints [DAS28] > 5.1), and comorbidities were collected through a structured questionnaire and medical record review. Comorbidities were quantified by the Charlson Comorbidity Index (CCI). Logistic regression analyses were used to identify associated factors. Results A total of 646 (98.9%) patients had ≥ 1 comorbidity. The most prevalent were dyslipidemia (75.8%), obesity (58.7%), hypertension (42.7%), type 2 diabetes mellitus (30.3%), and osteoporosis (OP; 15.6%). Age ≥ 45 years was independently associated with coronary artery disease (odds ratio [OR] 9.71, 95% CI 1.91-178.00), OP (OR 19.60, 95% CI 5.96-121.00) and infectious diseases (OR 1.60, 95% CI 1.03-2.54). Female sex was associated with lower cardiovascular risk (OR 0.27, 95% CI 0.11-0.62), whereas female sex was associated with increased odds of OP (OR 3.55, 95% CI 1.71-8.37) and gastrointestinal (GI) disorders (OR 2.18, 95% CI 1.37-3.56). The use of targeted synthetic and biologic disease-modifying antirheumatic drugs increased the risk of infection (OR 14.80 and 4.11, respectively). High DAS28-CRP and ESR values were linked to GI comorbidities. The CCI survival index was significantly lower in older patients (≥ 45 years; mean 68.7 [SD 26.7]) than in younger patients (mean 93.3 [SD 6.7], P < 0.001). Conclusion The prevalence of multimorbidity is high among patients with RA in Bangladesh, particularly early cardiovascular disease risk.
A newsletter discute a necessidade de ajustar os pontos de corte dos índices CDAI e SDAI para a realidade brasileira, visando uma identificação mais precisa da remissão na artrite reumatoide e evitando o sobretratamento. Além disso, revisa as diretrizes de rastreio para doença pulmonar intersticial associada à AR e destaca o potencial condroprotetor da metformina em pacientes diabéticos com osteoartrite.
BACKGROUND: The myokines irisin and myostatin participate in bone and skeletal muscle homeostasis and may characterize the clinical status of these tissues. The study aimed to evaluate the association of myokines serum levels with one-year radiographic progression and lean mass in individuals with rheumatoid arthritis (RA). METHODS: Forty female individuals with RA, aged ≥ 18 years who met 2010 American College of Rheumatology criteria, and 30 individuals without RA and any chronical disease, matched by sex and body mass index (BMI) were included. Serum levels of irisin and myostatin were determined by immune assay. RA subjects had their radiographs of hands and feet evaluated by Sharp/van der Heijde score (SHS) at two timepoints, baseline and after one year. At baseline, disease activity was calculated by Disease Activity Score 28-C reactive protein (DAS28-CRP), body composition was evaluated using dual X-ray absorptiometry (DXA), muscle strength was assessed by handgrip test and chair rising test (CRT), and physical function was assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) and timed up and go (TUG) test. RESULTS: . Rapid radiographic progression and low lean mass were present in 17.5% and 14.8% of the RA individuals, respectively, and showed no correlation with irisin and myostatin. Myostatin was significantly lower in RA than in controls (3021.7 ± 1217.2 vs. 4049.0 ± 1610.0 pg/ml; p = 0.011), and individuals treated with biologic disease-modifying antirheumatic drugs (bDMARDs) showed higher irisin levels than individuals non-treated with bDMARDs (31.7 ± 7.6 vs. 25.7 ± 6.8 ng/ml; p = 0.033). RA duration was correlated with baseline SHS (r = 0.563; p = 0.001) and appendicular lean mass index (ALMI; r= -0.451; p = 0.004), and irisin levels were positively correlated with TUG
Abstract Introduction This study aimed to assess the impact of a 10-session hand massage protocol on hand function, grip strength, pinch strength, pain threshold, and tactile sensory threshold in patients with early-stage, seropositive rheumatoid arthritis (RA) without radiographic damage or hand deformity. Methods This study was a randomized controlled clinical trial. Thirty female RA patients with a diagnosis time of less than two years, seropositive, with low disease activity/remission, and without active arthritis in their hands were included in the study. Participants were randomized 1:1 to intervention and control groups. The intervention group underwent 10 hand massage sessions over a two-week period, in addition to regular medical care. The control group received only regular medical care. All assessments were performed at baseline (T1) and at week 2 (T2). Outcome measures included hand grip strength, pinch strength, pain threshold (dolorimetry), tactile sensory threshold (Semmes-Weinstein monofilament test), Duruöz Hand Index (DHI), and patient global assessment (PGA). Results A total of 30 RA patients were included in the study (intervention group, n = 15; control group, n = 15). At baseline, no significant differences were observed between the groups in demographic, laboratory, or clinical characteristics ( p > 0.05). In the intervention group, significant improvements in hand grip strength and pinch force were observed at T2 compared with baseline ( p = 0.008 and p = 0.023, respectively). Median hand grip strength increased from 55 (40–75) to 65 (45–80) kg, and median pinch strength increased from 15 (6–18) to 16 (11–21) kg. No significant alterations were noted in these parameters within the control group ( p > 0.05). In the control group, median hand grip strength was 45 (25–80) kg at baseline and
Objective Interstitial lung disease is an important extra‐articular manifestation of rheumatoid arthritis (RA) associated with high mortality and morbidity. Lung ultrasound (LUS) has recently emerged as a possible screening tool. We assessed the role of lung ultrasound in monitoring radiological progression and the development of new interstitial lung abnormalities (ILA). Methods In this prospective pilot study, RA patients underwent high‐resolution CT (HRCT), pulmonary function tests (PFTs), symptom assessment, and LUS at baseline and 12–18 months later. B‐lines were quantified using a 72‐zone protocol. Radiological changes across longitudinal HRCTs were scored on a 5‐point Likert scale by blinded thoracic radiologists. Six multivariable logistic regression models were built to predict HRCT progression, using combinations of LUS parameters, PFTs, symptoms, and clinical characteristics. Results 81 patients completed the follow‐up HRCT and per‐protocol LUS was performed in 95% (77/81). Radiological progression was observed in 31% (25/81). An increase in B‐lines was significantly associated with radiological progression (p=0.018), and a linear trend was confirmed (p=0.026). In multivariable analysis, both baseline B‐lines (p=0.029) and the change in B‐lines over time (p=0.012) significantly predicted progression (AUC=0.78, 95% CI: 0.64–0.92). When combining LUS and change in DLCO (AUC=0.82, 95% CI: 0.70–0.94), the model fit remained similar, and outperformed symptom scores (AUC=0.58, 95% CI 0.40–0.75, p=0.020) and PFTs (AUC=0.59, 0.44–0.74, p=0.022). Conclusion LUS may be a useful, radiation‐free tool to monitor and predict radiological progression of ILA in RA. These findings support further research into integrating LUS into longitudinal RA‐ILD assessment, particularly as part of a multimodal approach. image
The aim of this study was to evaluate the frequency of overactive bladder syndrome (OAB) in patients with rheumatoid arthritis (RA) and its relationship with clinical parameters and central sensitization (CS). This cross-sectional study included 95 patients diagnosed with RA according to the 2010 ACR/EULAR criteria and 95 healthy controls. OAB symptoms were assessed using the Overactive Bladder Questionnaire–Version 8 (OAB-V8). Pain intensity was assessed using the Visual Analog Scale (VAS), disease activity using the Disease Activity Score in 28 joints (DAS-28), functional status using the Health Assessment Questionnaire (HAQ-DI), quality of life using the Quality of Life–Rheumatoid Arthritis (RA-QoL), and CS Central Sensitivity Inventory Section A (CSI-A). OAB was detected in 54.7% of patients with rheumatoid arthritis, while this rate was 17.9% in the control group (p < 0.001). Multivariable logistic regression analysis showed that RA was independently associated with OAB after adjustment for age, BMI, and smoking status (adjusted OR: 5.37, 95% CI: 2.75–10.53, p < 0.001). When RA patients were evaluated according to the presence of OAB, age (p = 0.019), education level (p = 0.007), pain intensity (VAS) (p = 0.046), functional status (HAQ-DI) (p = 0.002) and CS scores (p < 0.001) were significantly higher in patients with OAB. Correlation analyses showed significant associations between OAB-V8 scores and pain (p < 0.001), functional status (p = 0.001), quality of life (p = 0.021), and CS scores (p < 0.001). In the regression analysis performed among RA patients, CS was independently associated with OAB (OR: 1.048, 95% CI: 1.009–1.089, p = 0.017). The prevalence of OAB is significantly higher in patients with RA. CS appears to be independently associated with OAB in this population, suggesting that
Assessing the presence and degree of synovitis is the cornerstone of managing patients with arthritis. Ultrasound has been shown to be a valuable tool for this in routine care, and several scoring systems have been developed over time. Although there is an overall good validity across several different semi-quantitative scoring systems, they lack reliability when applied in the same patient cohort, emphasising the need for a consensus-based scoring system. A European Alliance of Associations for Rheumatology (EULAR) and Outcome Measures in Rheumatology (OMERACT) collaboration developed, almost 10 years ago, the consensus-based EULAR-OMERACT scoring system, which has subsequently been validated. It has face and content validity as it makes sense and allows to visualise all components constituting the synovitis complex. It has discriminant validity as it is sensitive to change during treatment, can discriminate between active treatment and placebo in clinical trials and has a moderate-to-excellent inter-observer and intra-observer reliability. It has construct validity by showing a parallel improvement in ultrasound sum scores and Disease Activity Score 28 and joint assessment, respectively. It has criterion validity with a predictive validity for biological disease-modifying antirheumatic drug (bDMARD) discontinuation and for flares while tapering bDMARDs. In addition, a correlation between the scoring system and histological inflammation was established. Finally, the EULAR-OMERACT scoring system is feasible, as a 24-joint assessment can be performed in 20 min. In conclusion, the EULAR-OMERACT scoring system is a valid scoring system that also fulfils the OMERACT 2.1 filter for instrument selection.
Despite differences in patient profiles and treatment patterns, molecular-targeted therapy managed by orthopaedic surgeons achieved comparable effectiveness and was associated with a lower risk of discontinuation due to adverse events compared with rheumatology care. Key Points • Patients managed by orthopaedic surgeons had longer disease duration, higher seropositivity, and more advanced structural and functional impairment than those managed by rheumatologists. • Despite these differences, treatment effectiveness and disease activity improvement with bDMARDs or JAK inhibitors were comparable between specialties after adjustment for confounders. • Treatment discontinuation due to adverse events was less frequent in patients managed by orthopaedic surgeons. • Guideline-based management may enable consistent clinical outcomes across different specialties in real-world rheumatoid arthritis care.
Rheumatoid arthritis (RA) is characterized by immune-mediated inflammation resulting in excess cardiovascular disease (CVD) risk. Increased sodium, decreased potassium intake and their ratio have been acknowledged as CVD risk modifiers, while pathophysiological studies suggest a role in autoimmunity and inflammation. We aimed to review in a systematic manner the literature regarding the effects of dietary sodium, potassium intake and their ratio, on cardiovascular and disease-related outcomes in patients with RA. We performed a systematic literature search in Medline and Cochrane. Our research concluded to 1,283 patients (8 studies). Although not all studies coincide, most agree that increased dietary sodium and reduced dietary potassium intake are adversely associated with disease related (rheumatic and immunologic) outcomes. The ratio between sodium and potassium emerges a potential indicator of autoimmunity state that needs to be further balanced. Only 4 studies reported associations with cardiovascular outcomes in RA, particularly hypertension, although not consistently and none with hard CVD endpoints. These findings support that interventions promoting a poor in sodium and rich in potassium diet in RA may have beneficial effects in terms of autoimmunity regulation, suppression of inflammation and improvement in cardiovascular health.
We have updated the Canadian Rheumatology Association (CRA) guidelines for rheumatoid arthritis (RA) with a significant addition and expansion to an existing recommendation addressing the dose reduction/tapering and discontinuation of disease-modifying antirheumatic drugs (DMARDs). New recommendations now encompass conventional synthetic, targeted synthetic, and biologic DMARDs.
Isolated anti-SSB positivity is associated with a significantly lower likelihood of Sjögren disease, SLE, and RA. These findings suggest that isolated anti-SSB may lack diagnostic utility and could represent a clinically insignificant serologic finding in many patients.
Pain is a debilitating and persistent symptom of rheumatoid arthritis (RA), associated with impaired functional capacity and reduced quality of life. Despite targeted disease-modifying treatments, many RA patients experience persistent pain, suggesting mechanisms operating independently of classic inflammatory pathways. Psychological factors, such as depression and anxiety, can impact patterns of appraisal and behavioral coping strategies. Understanding how these associations underpin pain symptoms in RA is key for developing targeted symptom management interventions. Using data from the Patient-Reported Outcomes in patients with Persistent Rheumatoid Arthritis (PROsPer-RA) cohort, pain trends were assessed over 12 months following disease-modifying adjustment, mapping these against socioeconomic, psychological, and behavioral factors to identify associations and mechanisms. This prospective study followed RA patients recruited to PROsPer-RA switching or escalating disease-modifying treatment. Clinical and patient-reported outcomes were collected at baseline, 3, and 12 months, including disease activity, joint pain (visual analog scale), widespread pain index (WPI), depression and anxiety symptoms, and cognitive and behavioral responses to symptoms. Latent growth curve models estimated associations between predictor variables and pain outcomes at baseline and over time. Mediation analyses examined whether cognitive and behavioral responses mediated the relationship between depression/anxiety symptoms and pain outcomes. Among 209 eligible patients, baseline joint pain was 49.8$\:\pm\:$24.9 out of 100 (worst pain) and WPI was 4.9$\:\pm\:$3.6 out of 17 areas, which persisted at similar levels at 3 and 12 months. Higher baseline pain was associated with male gender, financial stress, lower education, and unemployment. Higher levels in both pain outcomes associated with worse depression and anxiety symptoms at baseline and over time. Avoidance-based behavioral responses, particularly fear avoidance, were associated with worse pain and mediated the relationship between depression/anxiety symptoms and both pain outcomes. In this