Clinical Rheumatology[JOURNAL]
Sun
200 papers
Sacroiliac joint bone marrow edema as a biomechanical barometer: insights from the "natural experiment" of osteonecrosis of the femoral head.
Papastathopoulou NS, Ciaffi J, Mancarella L … +4 more , Facchini G, Carta M, Miceli M, Ursini F
Clin Rheumatol · 2026 Jun · PMID 42286264 · Publisher ↗
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Amyloidosis awareness and colchicine adherence in patients with familial Mediterranean fever: a cross-sectional study in an endemic region.
Dincses-Nas E, Batibay S, Bozkurt T … +3 more , Igneci E, Akyol SG, Kasapoglu E
Clin Rheumatol · 2026 Jun · PMID 42283984 · Publisher ↗
INTRODUCTION: Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disease, and secondary amyloidosis remains its most serious complication. We aimed to investigate amyloidosis awareness, col...
INTRODUCTION: Familial Mediterranean Fever (FMF) is the most common hereditary autoinflammatory disease, and secondary amyloidosis remains its most serious complication. We aimed to investigate amyloidosis awareness, colchicine adherence and related factors among FMF patients. METHODS: In this cross-sectional single-center study, patients with FMF completed a face-to-face questionnaire assessing amyloidosis awareness using structured questions and colchicine adherence through self-reported medication use. Demographic and clinical data were obtained from medical records. Factors associated with amyloidosis awareness and colchicine adherence were evaluated using univariate and multivariable analyses. RESULTS: A total of 185 patients were included; 64% were female. The median age was 38 years and disease duration was 13 years. Regular colchicine use was reported by 144 (78%) patients and was associated with awareness of its importance, older age, higher colchicine dose, and fewer attacks. Only 51 (27%) patients were completely or partially aware of amyloidosis, whereas 153 (83%) were aware of the risk of renal failure. Amyloidosis awareness was associated with younger age and higher education level. In multivariable analysis, regular colchicine use was independently associated with fewer attacks and a higher daily colchicine dose; while amyloidosis awareness was independently associated with awareness of the amyloidosis risk related to irregular colchicine use. CONCLUSION: Awareness of amyloidosis remains insufficient among patients with FMF, although colchicine adherence was high. Targeted educational strategies may be needed to improve awareness of amyloidosis and its prevention. Key Points • Awareness of amyloidosis was limited (27%) and was associated only with awareness of the amyloidosis risk related to irregular colchicine use. • Treatment adherence is closely linked to higher colchicine dose and fewer attacks.
Beyond the Glands: Extraglandular Manifestations Associated With Sicca Symptoms in Systemic Sclerosis.
Koletsos N, Trentzidis K, Gerolymatou N … +2 more , Drosos AA, Voulgari PV
J Clin Rheumatol · 2026 Jun · PMID 42275177 · Publisher ↗
BACKGROUND/OBJECTIVE: Sicca symptoms, including ocular and oral dryness, are frequently reported among patients with systemic sclerosis (SSc). Yet most studies have focused on patients with associated Sjögren disease (Sj...
BACKGROUND/OBJECTIVE: Sicca symptoms, including ocular and oral dryness, are frequently reported among patients with systemic sclerosis (SSc). Yet most studies have focused on patients with associated Sjögren disease (SjD) and data on SSc patients with isolated sicca symptoms remain limited. Therefore, we aimed to (i) investigate the characteristics of SSc patients with and without sicca symptoms, after excluding individuals with associated SjD or other potential causes of dryness, and (ii) identify factors independently associated with the presence of sicca manifestations. MATERIALS AND METHODS: This single-center retrospective observational study included consecutive SSc patients attending the Department until December 2024. Demographic, clinical and serological data were extracted from medical records. Sicca symptoms were defined as the presence of either dry eye or dry mouth symptoms documented in the medical records, using a structured approach. Multivariable logistic regression analysis was performed to determine variables significantly associated with sicca symptoms. RESULTS: In total, 237 SSc patients were included, 25.7% of whom reported sicca symptoms. In univariate analysis, age, female sex, arthralgias, left ventricular diastolic dysfunction (LVDD), and ratio of residual volume to total lung capacity (RV/TLC) ≥40% were associated with sicca symptoms. In multivariate analysis, only female sex [OR: 4.808 (95% CI: 1.088-15.308)] and RV/TLC≥40% [OR: 4.413 (95% CI: 1.982-9.826)] remained independent predictors of sicca manifestations. CONCLUSION: Sicca symptoms are common in SSc, even in the absence of SjD, and are characterized by female predominance and small airway involvement. SSc patients with isolated sicca symptoms may represent a distinct clinical phenotype.
Bilateral Femoral Head Avascular Necrosis With Crescent Sign.
Walrond A, Flower C
J Clin Rheumatol · 2026 Jun · PMID 42275176 · Publisher ↗
A 27-year-old man with lupus nephritis on long-term corticosteroid therapy presented with progressive bilateral hip pain and restricted hip movement. Radiographs demonstrated bilateral femoral head flattening, sclerosis,...
A 27-year-old man with lupus nephritis on long-term corticosteroid therapy presented with progressive bilateral hip pain and restricted hip movement. Radiographs demonstrated bilateral femoral head flattening, sclerosis, and subchondral crescent signs consistent with advanced avascular necrosis (AVN) with subchondral collapse. Steroid-induced AVN results from microvascular compromise and increased intraosseous pressure, leading to osteocyte death and trabecular collapse. Given advanced disease, bilateral total hip arthroplasty was advised.
Multilevel Axial Gout: Dramatic Response to IL-1 Inhibition.
Zulfiqar F, Gertner E
J Clin Rheumatol · 2026 Jun · PMID 42275146 · Publisher ↗
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Identification of diagnostic and prognostic hub genes in osteoarthritis: an integrated bioinformatics study.
Xu Y, Yang C, Wan M … +6 more , Lan S, Liu P, Li Z, Fang H, Gao T, Bi Y
Clin Rheumatol · 2026 Jun · PMID 42274933 · Publisher ↗
BACKGROUND: Osteoarthritis (OA) is a heterogeneous whole-joint disease and a leading cause of pain and disability worldwide. Synovial inflammation plays a critical role in OA progression, yet the underlying mechanisms re...
BACKGROUND: Osteoarthritis (OA) is a heterogeneous whole-joint disease and a leading cause of pain and disability worldwide. Synovial inflammation plays a critical role in OA progression, yet the underlying mechanisms remain unclear and reliable diagnostic biomarkers are lacking. OBJECTIVES: To identify synovium-based diagnostic biomarkers and explore the molecular mechanisms associated with OA using integrated bioinformatics, machine learning, and experimental validation. METHODS: Synovial gene expression profiles from OA and normal controls were integrated and analyzed after normalization and batch-effect correction. Differentially expressed genes (DEGs) were identified, followed by immune infiltration analysis and weighted gene co-expression network analysis. Candidate diagnostic biomarkers were screened using least absolute shrinkage and selection operator, random forest, and support vector machine-recursive feature elimination. Protein-protein interaction network analysis, external dataset validation, and experimental validation in an OA mouse model were further performed. RESULTS: We identified 574 DEGs and observed marked immune microenvironment remodeling in OA synovium. Integrative analysis yielded 54 candidate genes, from which CX3CR1, KLF9, and MCL1 were identified as candidate diagnostic biomarkers. In the training cohort, these genes showed strong diagnostic performance, with AUCs of 0.983, 0.985, and 0.975, respectively. Network analysis identified 41 interacting genes mainly enriched in inflammation- and tissue remodeling-related pathways. External validation showed that KLF9 had the most robust diagnostic performance. CONCLUSION: OA synovium is characterized by substantial immune remodeling and activation of inflammation-related pathways. CX3CR1, KLF9, and MCL1 may serve as candidate diagnostic biomarkers for OA, with KLF9 showing the strongest external validation performance. Key Points • Integrated synovial transcriptomic and bioinformatics analyses identified OA-related differentially expressed genes and co-expression modules. • WGCNA combined with LASSO, SVM-RFE, and RF identified CX3CR1, KLF9, and MCL1 as candidate diagnostic biomarkers for OA. • PPI analysis revealed 41 interacting genes mainly involved in inflammation- and tissue remodeling-related pathways. • Immune infiltration analysis demonstrated substantial synovial immune microenvironment remodeling in OA, supporting a role for immune dysregulation in disease progression.
GLP-1-based therapy and ICD-10-documented heart failure or respiratory failure events in non-diabetic adults with rheumatoid arthritis and obesity: a TriNetX federated cohort study.
Loizidis G, Summer R
Clin Rheumatol · 2026 Jun · PMID 42274932 · Publisher ↗
INTRODUCTION/OBJECTIVES: Glucagon-like peptide-1 (GLP-1)-based therapies have emerged as a major advance in cardiometabolic care; however, no prospective outcomes data exist for these agents in non-diabetic adults with r...
INTRODUCTION/OBJECTIVES: Glucagon-like peptide-1 (GLP-1)-based therapies have emerged as a major advance in cardiometabolic care; however, no prospective outcomes data exist for these agents in non-diabetic adults with rheumatoid arthritis (RA) and obesity. We examined whether GLP-1-based therapy was associated with first post-landmark ICD-10-documented heart failure (HF) or respiratory failure (RF) events. METHODS: We conducted a retrospective cohort study in the TriNetX US Collaborative Network. Adults with RA, body mass index ≥ 30 kg/m, and baseline-year disease-modifying antirheumatic drug (DMARD) therapy were included; patients with diabetes and overlapping systemic autoimmune diseases were excluded. Exposure was semaglutide or tirzepatide documented within 0-90 days after the index BMI, and comparators were strict never-users. Cohorts were propensity score-matched 1:1 on 68 covariates. The primary endpoint was the first post-landmark ICD-10-documented HF or RF during days 91-365 among patients without pre-index documentation of the corresponding endpoint. RESULTS: After matching, 3483 patients remained per cohort, with all standardized mean differences < 0.10. During days 91-365, the primary endpoint occurred in 23/3176 GLP-1 users (0.7%) and 57/3144 never-users (1.8%) (hazard ratio (HR): 0.48; 95% confidence interval (CI): 0.30-0.78; p = 0.002; absolute risk difference: - 1.1 percentage points). The HF and RF components showed directionally similar associations. Findings were directionally similar at extended follow-up and, where estimable, in the calendar-time-restricted analysis. Bias probes showed no differential utilization. CONCLUSIONS: GLP-1-based therapy was associated with substantially lower hazards of first post-landmark ICD-10-documented HF or RF events. These observations, while compelling, are hypothesis-generating and require prospective validation before informing clinical use. Key Points • In a propensity score-matched TriNetX cohort of non-diabetic adults with rheumatoid arthritis and obesity, GLP-1-based therapy was associated with a lower hazard of first post-landmark ICD-10-documented heart failure or respiratory failure events. • In absolute terms, the primary composite occurred in 0.7% of GLP-1 users and 1.8% of never-users during days 91-365, corresponding to approximately one fewer event per 100 patients. • Heart failure and respiratory failure, analyzed separately, showed directionally consistent lower hazards, although event counts were small. • The findings provide preliminary RA-specific evidence for a prospective study, but they should not be used to guide treatment decisions.
Guide from the Colegio Mexicano de Reumatología for the Pharmacological Treatment of Systemic Sclerosis Part 1: Cutaneous Involvement, Interstitial Lung Disease, and Pulmonary Arterial Hypertension.
Chacón-Abril K, Portela-Hernández M, Fajardo-Hermosillo LD … +18 more , Limón-Camacho L, Ruiz-Gómez NI, Pacheco-Tena C, Barrera-Rodríguez AA, Vera-Lastra O, Mejía M, Buedía-Roldán I, Martínez-Espinosa K, Mateos H, Méndez Flores S, Pulido-Zamudio T, Zayas-Hernández N, García-Cuellar JA, Navarro-Vergara D, Rojas-Serrano J, Medrano-Ramírez G, Rodríguez-Reyna TS, Systemic Sclerosis Guidelines Committee of the Colegio Mexicano de Reumatología
Reumatol Clin (Engl Ed) · 2026 May · PMID 42270533 · Publisher ↗
Systemic sclerosis (SSc) is a severe autoimmune disease characterized by fibrosis, inflammation, and vasculopathy, with high morbidity and mortality. Cutaneous involvement is an important marker of disease severity, whil...
Systemic sclerosis (SSc) is a severe autoimmune disease characterized by fibrosis, inflammation, and vasculopathy, with high morbidity and mortality. Cutaneous involvement is an important marker of disease severity, while interstitial lung disease and pulmonary arterial hypertension represent the leading causes of death. This manuscript presents the first national pharmacologic treatment guideline, developed using the GRADE methodology and structured around a flexible, stepwise therapeutic algorithm. Unlike international guidelines, this proposal prioritizes clinical applicability and context-specific decision-making, given the heterogeneity of resources and access to treatments within our healthcare system. The guideline was developed by a multidisciplinary panel including rheumatologists, dermatologists, pulmonologists, cardiopulmonologists, and methodologists. Authors formulated ten PICO questions, and a systematic search was conducted in PubMed, Cochrane Library, EMBASE, and LILACS (2006-February 2024), including key earlier literature. Of 594 records identified, 114 studies were ultimately included after evaluation using the GRADE methodology. Steroids, immunosuppressants, immunomodulators, hematopoietic stem cell transplantation, and vasodilators were assessed. A total of 26 recommendations were issued and subjected to Delphi consensus, with agreement defined as ≥80% acceptance.
Analysis of drug use and expenditure of conventional and biological disease-modifying anti-rheumatic drugs: a study from Northwest China.
Ni DH, Gao D, Sun ZH … +2 more , Zhu LH, Ren Y
Clin Rheumatol · 2026 Jun · PMID 42268488 · Publisher ↗
OBJECTIVE: This study evaluates the impact of China's National Centralized Drug Procurement policy on DMARD accessibility, cost-effectiveness, and utilization patterns in a regional rheumatology institute in Northwest Ch...
OBJECTIVE: This study evaluates the impact of China's National Centralized Drug Procurement policy on DMARD accessibility, cost-effectiveness, and utilization patterns in a regional rheumatology institute in Northwest China, while examining the interplay between pricing policy and COVID-19 disruptions. METHODS: Data were sourced from our hospital information management system (HIS) from 2018 to 2022, encompassing prescribing records for approximately 70,000 annual outpatient rheumatology visits. DMARDs were classified into three groups: conventional synthetic DMARDs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), and biological DMARDs (bDMARDs). Total revenue, defined daily doses (DDD), and defined daily dose costs (DDDc) were calculated, and compound annual growth rates (CAGR) were analyzed. RESULTS: The CAGR of total revenue of DMARDs from 2018 to 2022 was 0.91%. Among csDMARDs, methotrexate for injection saw the largest revenue increase (CAGR of 92.26%). Recombinant human type II tumor necrosis factor receptor-antibody fusion proteins consistently led among tsDMARDs and bDMARDs. In contrast, infliximab experienced the largest decline (CAGR of - 23.49%). Leflunomide remained the most frequently used csDMARD, while several tsDMARDs and bDMARDs, except infliximab, showed upward trends, with baricitinib, tofacitinib, golimumab, and secukinumab exceeding 200% CAGR. CONCLUSIONS: National centralized procurement policy achieved dramatic cost reductions (e.g., tofacitinib DDDc decreased by 93.3%), directly driving increased utilization of tsDMARDs and bDMARDs. This study provides empirical evidence that aggressive pharmaceutical pricing policies can rapidly improve access to advanced rheumatologic therapies in resource-limited settings, offering a replicable model for healthcare systems worldwide. Key Points • Overall disease-modifying antirheumatic drugs (DMARDs) use showed modest growth from 2018 to 2022. • tsDMARDs and bDMARDs exhibited rapid increases in use and revenue. • Methotrexate and leflunomide remained key csDMARDs in clinical practice.
Cellular therapies in systemic lupus erythematosus: recent progress and future directions.
Daoud A, Pamuk ON
Clin Rheumatol · 2026 Jun · PMID 42260211 · Publisher ↗
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by dysregulated immune responses, chronic inflammation, and progressive organ damage. Despite substantial advances in understanding d...
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by dysregulated immune responses, chronic inflammation, and progressive organ damage. Despite substantial advances in understanding disease pathogenesis and the development of targeted therapies, a significant proportion of patients remain refractory to conventional immunosuppressive and biologic treatments, particularly those with severe or relapsing disease manifestations such as lupus nephritis. Persistent disease activity and cumulative treatment toxicity continue to contribute to irreversible organ damage and increased morbidity. Recent advances in cellular immunotherapy have positioned chimeric antigen receptor (CAR) T-cell therapy as a promising novel therapeutic approach in SLE. By targeting B-cell-associated antigens, CAR T-cell therapy enables deep and sustained B-cell depletion, potentially overcoming the limitations of monoclonal antibody-based B-cell-directed therapies. Early clinical reports and emerging trial data demonstrate that CD19-directed CAR T-cell therapy can induce profound immunologic remission and sustained, drug-free clinical remission in patients with refractory SLE. These findings suggest that CAR T-cell therapy may not only control disease activity but also fundamentally reset autoimmune immune responses. In this review, we summarize the immunopathogenic rationale for CAR T-cell therapy in SLE, review available preclinical and clinical evidence, and discuss ongoing efforts to develop more selective and safer CAR constructs targeting B-cell subsets relevant to lupus pathogenesis. We also address key challenges, including safety considerations, durability of response, patient selection, and long-term immunologic consequences. Collectively, CAR T-cell therapy represents a transformative and potentially disease-modifying strategy for SLE, warranting further investigation in well-designed clinical trials.
Rheumatic disease in Canada's Northwest Territories: baseline review and comparative insights.
Hung W, Azmi A, Katz S
Clin Rheumatol · 2026 Jun · PMID 42260210 · Publisher ↗
OBJECTIVES: This study captures baseline demographic and rheumatologic history of patients from Canada's Northwest Territories (NWT) to improve disease burden understanding, identify potential at-risk populations, and hi...
OBJECTIVES: This study captures baseline demographic and rheumatologic history of patients from Canada's Northwest Territories (NWT) to improve disease burden understanding, identify potential at-risk populations, and highlight care gaps in a unique and underserved population. METHODS: In this descriptive study, we collected retrospective data on patients referred from the NWT to Edmonton, Alberta, in 2022-2023, when all established and newly referred rheumatology patients from this region were redirected to receive care in Edmonton. Diagnoses were compared to a 2022-2023 Edmonton rheumatology new-patient cohort. RESULTS: There were 425 patients (70% female) representing 30 communities. Of the 250 patients with documented ethnicity, 69.6%, 25.6%, and 4.8% were of Indigenous, White, and Other descent (including people of Asian and African descent), respectively. The most frequent inflammatory rheumatologic diagnoses among new referrals were rheumatoid arthritis (27.8%), gout (13.9%), and psoriatic arthritis and ankylosing spondylitis (11.1% each, vs. ~ 7% each in the Edmonton-based cohort). There were no new vasculitis cases in the NWT cohort compared to 9.2% of new diagnoses in the Edmonton cohort. Twenty-one percent of patients missed their appointments, and 43% of previously established patients had active disease. CONCLUSION: This represents the broadest epidemiologic dataset for NWT patients with rheumatologic diseases, with higher observed proportion of ankylosing spondylitis and psoriatic arthritis and lower observed proportion of vasculitis, compared to the Edmonton cohort. NWT patients face unique barriers around geographic location, transportation, and care delays, compounded by active disease that may disproportionately affect female and Indigenous patients. Key Points • This study provides the broadest epidemiologic dataset of patients with rheumatologic diseases in the Northwest Territories and is the first to comprehensively differentiate between various rheumatologic diseases seen in this population. • There appears to be a higher observed proportion of psoriatic arthritis and ankylosing spondylitis, as well as a lower observed proportion of vasculitis, in patients from the NWT. This may reflect the heterogeneity of the population as well as heterogeneity among different Indigenous groups, but confirming and explaining these patterns requires further exploration. • This study further re-emphasizes known barriers that patients from the NWT face, including geographic location, transportation access, and delays to specialist care, all compounded by active disease that frequently requires medications that can only be prescribed by the respective specialist. • These limitations may disproportionately affect female and Indigenous patients.
Cytokine profiling reveals distinct inflammatory clusters and clinical correlations in antiphospholipid syndrome.
Liu X, Chen X, Zhu L … +7 more , Liu R, Dai S, Zhou Y, Guo J, Li C, Gan Y, Jia Y
Clin Rheumatol · 2026 Jun · PMID 42258072 · Publisher ↗
INTRODUCTION: Inflammatory immune activation is increasingly recognized as an important pathogenic component in antiphospholipid syndrome (APS). However, the clinical relevance of circulating cytokine alterations and the...
INTRODUCTION: Inflammatory immune activation is increasingly recognized as an important pathogenic component in antiphospholipid syndrome (APS). However, the clinical relevance of circulating cytokine alterations and their integrative immune patterns in APS remain incompletely understood. METHOD: Serum samples were obtained from 250 patients with APS and 81 healthy controls (HCs). Concentrations of 12 cytokines were measured using a multiplex bead-based immunoassay. Principal component analysis followed by K-means clustering was applied to identify cytokine-based subgroups among APS patients. Clinical manifestations and laboratory parameters were compared among clusters. RESULTS: Compared with HCs, patients with APS showed significantly elevated levels of IL-6, IL-8, IL-12p70, and IFN-γ, together with reduced levels of IL-5 and TNF-α (all P < 0.05). Unsupervised clustering based on cytokine profiles identified four distinct immune phenotypes among APS patients, characterized by low-inflammatory, pan-inflammatory, selectively enriched inflammatory (TNF-α/IL-5-abundant), and T-cell-priming (IL-12p70, IL-2, and IL-4). In particular, the pan-inflammatory cluster was associated with higher adjusted Global Antiphospholipid Syndrome Score (aGAPSS), greater anticardiolipin antibody positivity, and more pronounced hematologic abnormalities, whereas the T-cell-priming cluster was abundant for primary APS and exhibited relatively lower systemic inflammatory burden. CONCLUSIONS: APS is characterized by heterogeneous cytokine profiles reflecting distinct immune activation patterns. Cytokine-based clustering identifies clinically relevant inflammatory subgroups, supporting the potential value of immune stratification for improved risk assessment in APS. Key Points • Patients with APS exhibit a distinct circulating cytokine signature characterized by elevated IL-6, IL-8, IL-12p70, and IFN-γ with reduced IL-5 and TNF-α, underscoring the thrombo-inflammatory nature of the disease. • Unsupervised clustering of cytokine profiles identifies four immunologically distinct APS subgroups (low-inflammatory, pan-inflammatory, TNF-α/IL-5-abundant, and T-cell-priming), each associated with different clinical and laboratory features. • The pan-inflammatory cluster is linked to higher antiphospholipid antibody burden and greater hematologic abnormalities, whereas the T-cell-priming cluster is enriched for primary APS and exhibits a lower systemic inflammatory burden.
Real-world effectiveness and safety of firsekibart versus compound betamethasone in frequent gout flares: a multicenter retrospective study.
Chen M, Mou X, Wang W … +2 more , Jiang Q, Cheng Y
Clin Rheumatol · 2026 Jun · PMID 42258071 · Publisher ↗
INTRODUCTION: Acute gout flares cause severe pain and functional impairment, with limited options for patients intolerant to conventional therapies. Firsekibart, a novel anti-IL-1β monoclonal antibody, was approved in Ch...
INTRODUCTION: Acute gout flares cause severe pain and functional impairment, with limited options for patients intolerant to conventional therapies. Firsekibart, a novel anti-IL-1β monoclonal antibody, was approved in China in July 2025, but real-world evidence remains scarce. METHOD: This multicenter retrospective study enrolled 50 patients with acute gout flares (25 firsekibart 200 mg, 25 compound betamethasone 7 mg). Co-primary endpoints were VAS pain change at 48 h and time to first flare within 12 weeks. Secondary endpoints included pain at other timepoints, CRP change, flare frequency, and time to first flare within 24 weeks. Inverse probability weighting balanced baseline covariates, with weighted log-rank as primary analysis and Firth's penalized Cox regression for sensitivity analysis. RESULTS: Baseline characteristics were balanced. Pain relief was comparable between groups (P > 0.05). No firsekibart patients flared within 12 weeks vs. 11 (44.0%) on betamethasone. Weighted log-rank showed significantly lower flare risk with firsekibart (p < 0.001). Firth's penalized Cox confirmed a 97% risk reduction at 12 weeks (HR: 0.03; 95% CI: 0.01-0.59) and 88% at 24 weeks (HR: 0.12; 95% CI: 0.02-0.78). Median CRP decreased significantly with firsekibart (from 14.20 to 3.85 mg/L, P < 0.0001). Both treatments had acceptable safety profiles. CONCLUSIONS: In this real-world study of patients with frequent flares, firsekibart showed comparable analgesic efficacy to compound betamethasone and was associated with superior sustained flare prevention and acceptable safety. These findings suggest firsekibart may be a potential treatment option for patients with limited alternatives, though larger studies are warranted. Key Points • This study provides the first real-world evidence of firsekibart in acute gout flares. • Firsekibart showed comparable pain relief to compound betamethasone at 48 h. • Firsekibart reduced new flare risk by 88% within 24 weeks. • Firsekibart had an acceptable safety profile with no serious infections.
Machine learning-based prediction of 30-day mortality in critically ill patients with rheumatoid arthritis.
Liu J, Pan S, Xie H … +4 more , He J, Chen H, Wu Y, Chen Z
Clin Rheumatol · 2026 Jun · PMID 42258070 · Publisher ↗
BACKGROUND: Rheumatoid arthritis patients in the ICU face a high risk of mortality. While traditional ICU scoring systems are not specifically designed for the unique pathophysiological profile of RA. This study aimed to...
BACKGROUND: Rheumatoid arthritis patients in the ICU face a high risk of mortality. While traditional ICU scoring systems are not specifically designed for the unique pathophysiological profile of RA. This study aimed to develop a machine learning framework to accurately predict 30-day mortality for these patients. METHODS: Data from 400 RA patients in the MIMIC-IV database were analyzed. LASSO regression identified nine pivotal predictors: age, BUN (urea), PT, respiratory rate, SpO, glucose, urine output, and coronary artery disease. Six ML models were constructed using SMOTE to handle class imbalance. Performance was evaluated via AUC, sensitivity, and SHAP analysis for interpretability. RESULTS: The LR-SMOTE model demonstrated the best discriminative ability (AUC = 0.69), while the Stacking ensemble achieved the highest sensitivity (0.8). External validation on the eICU dataset yielded an AUC of 0.747 for the LR-SMOTE model. SHAP analysis identified urine output, CAD, and age as the most influential predictors. CONCLUSIONS: The machine learning framework demonstrates superior performance compared to most traditional scoring systems, while offering the distinct advantages of easier data acquisition and lower computational complexity. By leveraging readily accessible clinical parameters, it supports proactive, individualized clinical decision-making in the ICU.
Co-exposure to perchlorate, nitrate, thiocyanate, and per- and polyfluoroalkyl substances (PFAS) mixtures is associated with increased rheumatoid arthritis risk: a population-based cross-sectional study.
Yang Z, Wu Y, Tian F … +3 more , Bao J, Fan Y, Huang S
Clin Rheumatol · 2026 Jun · PMID 42258069 · Publisher ↗
BACKGROUND: Humans are concurrently exposed to a variety of environmental endocrine-disrupting chemicals (EDCs), which include such widespread substances like urinary perchlorates, nitrates, thiocyanates, and serum per-...
BACKGROUND: Humans are concurrently exposed to a variety of environmental endocrine-disrupting chemicals (EDCs), which include such widespread substances like urinary perchlorates, nitrates, thiocyanates, and serum per- and polyfluoroalkyl substances (PFAS). The vast majority of the previous studies were devoted to individual chemicals or certain groups of chemicals, but the impact of co-exposure to mixtures of EDCs was also not thoroughly studied. The objective of this study is to identify the relationship between these EDC mixtures and prevalence of rheumatoid arthritis (RA) based on NHANES database. METHODS: We used three types of regression models with individual chemical effects, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in 2005-2012 to analyze results of individuals aged ≥ 20 years. Age and gender subgroup analyses were also done. RESULTS: A total of 4219 patients were analyzed, and 215 (5.10%) of them had RA. Multivariate logistic regression demonstrated that there was a significant relationship between thiocyanate (as a continuous variable) and the prevalence of RA. The upper quartile of perchlorate, nitrate as well as thiocyanate and MPAH showed correlation with elevated prevalence of RA. The effects of specific chemicals were stronger among the older subjects and females. WQS and BKMR models showed a positive association between co-exposure to these chemicals and RA, with thiocyanate as the primary contributor. These associations were especially strong in young adults and females. CONCLUSION: This study provides the first evidence that co-exposure to a mixture of EDCs is positively correlated with RA, with a stronger effect in young adults and females. Thiocyanate is identified as a key contributor. Limiting exposure to EDCs may be beneficial for potentially reducing RA risk. Key Points • We assessed the association between a mixture of ten chemicals and the risk of incidence of RA. • The co-exposure of chemical mixtures were positively associated with RA by WQS and BKMR models. • Thiocyanate was the key contributor in these mixtures. • The associations were more pronounced among young adults and females.
Postmenopausal Osteoporosis, Endothelial Dysfunction, and Cardiovascular Risk.
Pickering ME, Heiss C, Morel V … +9 more , Pickering G, Couderc M, Mathieu S, Malochet-Guinamand S, Durif J, Sapin V, Pereira B, Tournadre A, Chapurlat R
J Clin Rheumatol · 2026 Jun · PMID 42257649 · Publisher ↗
BACKGROUND/OBJECTIVES: Bone and cardiovascular health are interconnected, yet their relationship with endothelial function in postmenopausal osteoporosis remains insufficiently understood. This study aimed to investigate...
BACKGROUND/OBJECTIVES: Bone and cardiovascular health are interconnected, yet their relationship with endothelial function in postmenopausal osteoporosis remains insufficiently understood. This study aimed to investigate, in women with osteoporosis, the associations between endothelial function, assessed by flow-mediated dilation (FMD), bone turnover, and cardiovascular disease risk. METHODS: This cohort study included consecutive postmenopausal osteoporosis outpatients from the Rheumatology Department of Clermont-Ferrand University Hospital, France. FMD was measured at the brachial artery and values contextualized with age-matched healthy women's data reported in the literature. Associations between FMD and bone-related parameters (bone mineral density, bone markers, fracture history, and treatments), and Systematic Coronary Risk Evaluation (SCORE2/2-OP) were analyzed. RESULTS: A total of 111 postmenopausal women with osteoporosis (mean age 69.4 ± 7.9 y; mean FMD=3.14 ± 2.28%) were included. No significant associations were found between FMD and bone-related parameters. FMD was positively associated with prior bisphosphonate use (r=0.270, p=0.007) and inversely associated with SCORE2/2-OP (r=-0.212, p=0.035), particularly among younger participants. Overall, 49.5% of patients had high/very high SCORE2/2-OP, and 55% of those classified as low/intermediate SCORE2/2-OP exhibited low FMD values. CONCLUSIONS: Measurement of the endothelial function in postmenopausal osteoporosis brings additional information to cardiovascular risk calculation, suggesting that factors beyond traditional cardiovascular risk determinants contribute to vascular impairment. In clinical practice, our findings support cautious cardiovascular follow-up even in osteoporotic patients with low cardiovascular risk and underline possible positive effects of bisphosphonates on endothelial function.
The relationship between hematological indices of systemic inflammation and disease activity in patients with rheumatoid arthritis: a retrospective cross-sectional study.
Nourmohammadi Z, Olfatifar M, Ahmadi MR … +7 more , Motaghi R, Jazi K, Masoumi M, Khodadadi ZH, Ehsani M, Khodaee A, Shajari R
Clin Rheumatol · 2026 Jun · PMID 42252375 · Publisher ↗
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 assess...
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.
Association between systemic oxidative stress imbalance and inflammatory markers in gouty patients: a cross-sectional case-control study in Yemen.
Alqadhi YA
Clin Rheumatol · 2026 Jun · PMID 42250201 · Publisher ↗
BACKGROUND: Gout is increasingly recognized as a systemic metabolic and inflammatory disorder. The urate paradox-where uric acid shifts from a plasma antioxidant to an intracellular pro-oxidant-remains a clinical challen...
BACKGROUND: Gout is increasingly recognized as a systemic metabolic and inflammatory disorder. The urate paradox-where uric acid shifts from a plasma antioxidant to an intracellular pro-oxidant-remains a clinical challenge in managing systemic complications. OBJECTIVE: This study evaluates the association between systemic oxidative stress imbalance and high-sensitivity C-reactive protein (hs-CRP) as a marker of inflammatory burden in gouty patients. METHODS: A case-control study was conducted on 200 participants (100 gouty patients and 100 healthy controls) in Yemen. Biomarkers including malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione (GSH), and hs-CRP were quantified. Multivariate linear regression was used to assess the independent predictive value of MDA for hs-CRP. RESULTS: Gouty patients exhibited significantly elevated MDA (6.45 ± 1.55 nmol/mL) and hs-CRP (14.2 ± 5.1 mg/L) compared to controls (P < 0.001). Conversely, a profound depletion in TAC and GSH was observed. A statistically significant positive correlation (r = 0.78, P < 0.001) was observed between MDA and hs-CRP. In multivariate analysis, MDA remained a significant independent associate, explaining approximately 61% of the variance in hs-CRP levels (R = 0.61, P < 0.001). CONCLUSION: Gout is characterized by a significant systemic oxidative stress imbalance which is independently associated with systemic inflammation. Clinical management should transcend urate-lowering therapy to include strategies aimed at restoring antioxidant capacity to mitigate systemic inflammatory damage. Key Points • Gouty patients exhibit a profound state of systemic redox exhaustion, characterized by depleted antioxidant defenses. • Lipid peroxidation (MDA) is strongly associated with the systemic inflammatory burden (hs-CRP) in gouty cohorts. • The robust correlation between oxidative stress and inflammatory markers suggests their potential as biomarkers for assessing disease status. • Systemic inflammation in gout appears to be closely linked to the severity of oxidative stress imbalance.
Handling missing data in fibromyalgia clinical trials-considerations for the use of linear mixed models in longitudinal analyses: perspectives in rheumatology.
Pontes-Silva A, Dibai-Filho AV, Avila MA
Clin Rheumatol · 2026 Jun · PMID 42250200 · Publisher ↗
OBJECTIVE: To critically examine current statistical practices for handling missing data in fibromyalgia randomized controlled trials (RCTs) and to provide practical guidance for the implementation of linear mixed models...
OBJECTIVE: To critically examine current statistical practices for handling missing data in fibromyalgia randomized controlled trials (RCTs) and to provide practical guidance for the implementation of linear mixed models (LMMs). METHODS: This methodological and narrative perspective reviews recent RCTs in fibromyalgia, highlighting common limitations in the handling of missing data and longitudinal analyses. We contrast traditional approaches, such as repeated-measures ANOVA, with LMM-based strategies within the intention-to-treat (ITT) framework. Additionally, we provide a step-by-step guide for implementing LMMs in SPSS. RESULTS: Evidence indicates that many fibromyalgia RCTs continue to rely on suboptimal statistical methods, including the exclusion of participants with incomplete data and the use of ANOVA-based approaches. These practices may reduce consistency with the ITT principle, decrease statistical efficiency, and contribute to potentially biased treatment effect estimates. In contrast, LMMs can incorporate partially observed longitudinal data, explicitly model within-subject correlations, and accommodate unbalanced longitudinal designs under the Missing At Random (MAR) assumption. However, their validity depends on correct model specification and the plausibility of underlying assumptions. CONCLUSIONS: The persistent gap between methodological recommendations and analytical practices in fibromyalgia RCTs may compromise the interpretability and reliability of treatment effect estimates. LMMs may represent a more flexible and methodologically appropriate approach for longitudinal analyses involving incomplete follow-up data, particularly when aligned with study design characteristics and available statistical expertise. Improving statistical rigor in this field remains essential to support more reliable clinical interpretation and evidence-informed decision-making.
Effect of different folic acid doses on methotrexate-related toxicity and its association with erythrocyte methotrexate-polyglutamates in patients with rheumatic diseases: a single-center exploratory randomized controlled trial.
Yoshida Y, Hosokawa Y, Taogoshi T … +9 more , Oka N, Kobayashi H, Kidoguchi G, Araki K, Ishitoku M, Sugimoto T, Mokuda S, Matsuo H, Hirata S
Clin Rheumatol · 2026 Jun · PMID 42249242 · Publisher ↗
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...
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 associated with improved fatigue severity, indicating a potential therapeutic option for patients who develop fatigue.
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