RMD Open最新文献

Objective: To characterise patients with 'very early' axial spondyloarthritis (axSpA), defined as a duration ≤1 year of back pain and to determine the effectiveness of a first tumour necrosis factor inhibitor (TNFi) in very early versus established axSpA in a large observational registry.

Methods: We included a total of 3324 patients with axSpA from the Swiss Clinical Quality Management in Rheumatic Diseases registry with available data on duration of back pain (≤1 year=very early axSpA, n=441; >1 year and ≤2 years=early axSpA, n=218; >2 years=established axSpA, n=2575). A first TNFi was started in 31%, 38% and 36% of patients with very early, early and established axSpA. Adjusted logistic regression models were used to compare the probability of achieving low disease activity status according to the Axial Spondyloarthritis Disease Activity Score (ASDAS <2.1) at 1 year. Drug survival was analysed with multiple-adjusted Cox proportional hazards models. Missing data were handled using multiple imputation by chained equations.

Results: Objective signs of inflammation were more prevalent in very early disease. No difference was found regarding the achievement of ASDAS <2.1 after adjustment for age, sex, human leucocyte antigen-B27 status, education, body mass index, smoking, ASDAS and sacroiliac inflammation on MRI (OR 1.08, 95% CI 0.70 to 1.68 in very early vs established axSpA). Similarly, no significant difference in TNFi retention was found in very early versus established axSpA (HR for drug discontinuation 1.05, 95% CI 0.84 to 1.31).

Conclusion: We found no evidence for a better effectiveness of TNFi in patients with very early versus established axSpA.

Background: Psoriatic disease has a complex effect on bone metabolism, resulting in both pathological bone formation and bone resorption. However, microstructural changes in cortical and trabecular compartments remain poorly understood. The aim of this study was to investigate the prevalence and determinants of bone microarchitectural damage in patients with psoriatic disease.

Methods: We performed a cross-sectional study in patients with psoriasis (PsO), psoriatic arthritis (PsA) and age-matched healthy controls (HCs) recruited into the Department of Dermatology and Rheumatology of Verona centre. We conducted high-resolution peripheral quantitative CT of the radius and finger joints of the non-dominant hand. Bone microstructure parameters and finite element analysis (uFEA) were calculated.

Results: 51 patients with PsO and 39 patients with PsA were consecutively enrolled in the study. 24 age-matched HCs were enrolled. Distal radius total and cortical volumetric bone mineral density (Ct.BMD) levels were lower in patients with PsA and PsO compared with HC. On distal radius uFEA analysis, we found a significant reduction of stiffness in PsA compared with both HC and PsO. At the distal interphalangeal (DIP) joints, Ct.BMD and trabecular volumetric bone mineral density were lower in PsA and PsO compared with HC. Nail involvement in psoriatic disease was negatively associated with bone stiffness at the proximal and distal region of the DIPs.

Conclusion: Psoriatic disease negatively impacted bone integrity. Patients with psoriatic disease seemed to have lower bone density and more microarchitectural alteration that impacted on biomechanics properties. Nail involvement was associated with decreased bone stiffness in psoriatic disease.

Objective: To assess structural changes at peripheral entheses and the association with spinal bone formation in patients with long-standing radiographic axial spondyloarthritis (r-axSpA) overall and stratified by sex.

Methods: Peripheral entheses were examined cross-sectionally using ultrasound (US) in patients fulfilling the modified New York criteria for ankylosing spondylitis (AS) and assessed for Outcome Measures in Rheumatology consensus-based structural lesions (enthesophytes, calcifications and erosions) summed to a damage US score (0-42). Spinal radiographs were graded with the modified Stoke AS Spinal Score (mSASSS). Associations between US damage score and mSASSS were assessed with negative binomial regression analyses overall, by sex and by age quartiles.

Results: US was performed in 173 patients, 54% males, with a mean (SD) age of 55 (13) years and symptom duration of 29 (13) years. The prevalence of any structural US lesion was 92%. The US damage score was higher in males than females (mean (SD) 4.7 (3.0) versus 3.3 (2.4), p<0.001) and increased significantly with age, as did mSASSS. Univariate associations between US damage score and mSASSS were found overall and in males, but diminished with older age. The association remained significant for males when the multivariable model was adjusted for symptom duration (rate ratio (95% CI) for log-transformed mSASSS+1: 1.32 (1.04 to 1.67)). Overall, mSASSS was not associated with the US damage score when the multivariable model was adjusted for age or symptom duration.

Conclusion: Structural lesions at the peripheral entheses are common in long-standing r-axSpA and accumulate with age, which may obscure the possible association with spinal bone formation.

Objectives: MRI-detected subclinical inflammation in clinically suspect arthralgia (CSA) predicts progression to inflammatory arthritis (IA) and rheumatoid arthritis (RA) and is incorporated in EULAR/ACR risk stratification criteria. Conventional MRI is hampered by long scan times, intravenous contrast and high costs, while modified Dixon (mDixon) MRI, with 5 min scan time and no intravenous contrast, is much more feasible. To optimise mDixon MRI utility, we compared bilateral versus unilateral hand analysis for detecting subclinical inflammation. We also studied the distribution of subclinical inflammation in CSA.

Methods: 139 patients of the CSA Leiden cohort were included. mDixon MRIs of bilateral wrist and metacarpophalangeal 2-5 joints were scored for subclinical inflammation (synovitis/tenosynovitis/osteitis) using RA MRI scoring. The hand with the most self-reported painful joints was used for unilateral analysis. Patients were followed for ≥6 months, with IA and RA development assessed at 6 months. We compared prognostic performance of bilateral versus unilateral MRI-detected subclinical inflammation.

Results: Subclinical inflammation detected on bilateral MRI was more strongly associated with IA development than on unilateral MRI; 4.80 (95% CI 1.09 to 21.11) versus 2.34 (95% CI 0.84 to 6.49). Bilateral analysis resulted in a 25% higher sensitivity and 15% lower specificity, with a net 10% increase in correctly classified patients. Results for RA development were similar, with HRs of 8.17 (95% CI 1.06 to 62.86) versus 3.23 (95% CI 0.98 to 10.66), and 20% higher sensitivity. Subclinical inflammation was unilateral in 52% of patients and scanning one hand would miss a quarter of patients.

Conclusion: Bilateral MRI of the hands is preferable to unilateral MRI for detecting subclinical inflammation in CSA, because of its asymmetrical distribution.

Background: ¹⁸F-Fibroblast activation protein inhibitor ([¹⁸F]FAPI) positron emission tomography (PET)/CT is an emerging tool for detecting IgG4-related disease (IgG4-RD). However, standardised quantitative analysis and image scoring present ongoing challenges in patients with IgG4-RD.

Purpose: To establish organ-specific reference thresholds for IgG4-RD involvement on [¹⁸F]FAPI PET/CT images, and to develop a novel, clinically applicable scoring system to monitor disease activity in patients with IgG4-RD.

Methods: This retrospective study recruited 85 patients with IgG4-RD and 10 healthy individuals, all of whom underwent [¹⁸F]FAPI PET/CT. Organ-specific uptake thresholds were defined as [¹⁸F]FAPI uptake greater than the maximal standardised uptake value +3 SD in the corresponding anatomical regions of healthy individuals. Moreover, we developed a novel method, [¹⁸F]FAPI PET/CT Activity Score of IgG4-RD (FPAS-IgG4), for scoring disease activity using a logistic regression model with receiver operating characteristics curve analysis.

Results: Among 85 patients with IgG4-RD, 64 lesions suspected of IgG4-RD involvement were biopsied and 58 (90.6%) of these lesions were positive for IgG4. [¹⁸F]FAPI PET/CT achieved a sensitivity, specificity and accuracy of 86.2%, 83.3% and 85.9%, respectively, for detecting IgG4-RD based on organ-specific uptake thresholds. The active disease group had a higher FPAS-IgG4 than the inactive disease group (5.2±3.0 vs 1.7±1.3, p<0.0001). FPAS-IgG4 >2 showed a sensitivity of 93.2% and a specificity of 73.1% in distinguishing between active and inactive disease. Multivariable logistic regression analysis demonstrated that FPAS-IgG4 was strongly associated with active IgG4-RD (p=0.001).

Conclusion: [¹⁸F]FAPI PET/CT could be a valuable tool for monitoring the activity of IgG4-RD, aiding in disease stratification.

Objective: Autoimmune rheumatic diseases, including rheumatoid arthritis (RA), have recently been associated with an increased risk of cancer, particularly head and neck cancer (HNC). This study aimed to assess the risk of HNCs in patients with RA, focusing on the impact of serological status and specific HNC sites.

Methods: A retrospective cohort study was conducted using data from the Korean National Health Insurance Service. A total of 40 990 patients with RA were divided into seropositive and seronegative RA groups, matched with 204 950 non-RA controls. Cox proportional hazards models were used to calculate adjusted HRs (aHRs) for HNCs, adjusting for important covariates such as smoking, alcohol consumption and comorbidities.

Results: Patients with RA had an increased risk of overall HNCs (aHR: 1.53, 95% CI 1.12 to 2.09) compared with controls, with a significantly higher risk for pharyngeal cancer (aHR: 2.20, 95% CI 1.33 to 3.64). However, RA showed no significant association with oral, salivary or laryngeal cancer. The analysis stratified by seropositivity status revealed no significant difference in the risk of HNCs between seropositive and seronegative RA groups.

Conclusion: Patients with RA have an increased risk of developing overall HNCs, particularly pharyngeal cancer. However, no significant association was found for other HNC types. Further research is warranted to better understand the potential link between RA and increased pharyngeal cancer risk.

Objectives: To investigate the efficacy, safety, pharmacokinetics, immunogenicity and pharmacodynamics of combination therapy with nipocalimab and certolizumab in participants with active rheumatoid arthritis (RA) despite treatment with advanced therapies.

Methods: In this phase 2a study, participants were randomised 3:2 to receive combination therapy with nipocalimab (intravenous 30 mg/kg) and certolizumab (subcutaneous 400 mg at weeks 0, 2, 4, then 200 mg) or certolizumab monotherapy every 2 weeks from weeks 0 to 24. The primary endpoint was change from baseline in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at week 12. Other outcomes were assessed through week 30.

Results: 103 participants were enrolled (combination therapy/monotherapy, n=62/41). At week 12, the primary endpoint was similar between groups (least squares mean 90% CI -1.92 (-2.48 to -1.36) vs -1.86 (-2.44 to -1.28); p=0.822). Secondary endpoints were also similar between groups, although numerically higher proportions of participants treated with combination therapy versus monotherapy achieved ≥50% response in American College of Rheumatology criteria (ACR50), DAS28-CRP <2.6 and DAS28-CRP ≤3.2 at week 12. Serious adverse events were reported in 11.3% of participants in the combination therapy group and 2.4% in the monotherapy group. In combination with certolizumab, nipocalimab exhibited nonlinear pharmacokinetics with accelerated clearance and substantially, reversibly reduced serum immunoglobulin G, including anticitrullinated protein antibody levels.

Conclusions: Combination therapy of nipocalimab with certolizumab showed a similar outcome in the primary endpoint and secondary endpoints compared with certolizumab monotherapy in participants with active RA.

Objectives: Current therapeutic paradigms for treatment-refractory rheumatic diseases rely on chronic immunosuppression with variable efficacy and potential for cumulative toxicity. We systematically synthesised evidence on the clinical efficacy, safety and durability of chimeric antigen receptor T-cell (CAR-T) therapy in autoimmune rheumatic diseases.

Methods: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO: CRD42025641602). Five databases were searched from inception to February 2025 for primary studies investigating CAR-T therapy in autoimmune rheumatic diseases. Two reviewers independently assessed studies using the Joanna Briggs Institute tools and the Risk of Bias in Non-Randomised Studies of Interventions tool.

Results: 12 studies encompassed 44 patients with severe treatment-refractory disease across six rheumatic conditions. Patients had extensive prior exposure (median 5 therapies), including conventional and biological agents. Cluster of Differentiation antigen 19 (CD19)-targeted constructs predominated (83% of studies), with emerging dual-target approaches (17%). Universal clinical responses were achieved (100% of studies; individual response rates 92%-100%), with complete responses occurring within 2-16 weeks. Sustained drug-free remissions extended 6-46 months, accompanied by profound autoantibody reductions (80%-99% across disease-specific markers). Safety profiles diverged markedly from oncological experience: cytokine release syndrome (CRS) remained exclusively confined to grades 1-2, while immune effector cell-associated neurotoxicity occurred in 25% of studies, with predominantly grade 1 severity.

Conclusions: CAR-T therapy demonstrates substantial efficacy in treatment-refractory rheumatic diseases, achieving sustained remissions through comprehensive B-cell elimination. Importantly, safety profiles were favourable, with CRS limited to grades 1-2 severity, no grade ≥3 events and rare immune effector cell-associated neurotoxicity, representing markedly superior tolerability compared with oncological applications.

Prospero registration number: CRD42025641602.

Objective: To develop and validate a predictive model for distinguishing controls (Ctr), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) based on nailfold videocapillaroscopy (NVC) image features.

Methods: A total of 600 NVC images from 396 participants (Ctr=117, RA=337 and SLE=146) were collected and divided into training and test sets at a 7:3 ratio. Nine NVC features were extracted, and an eXtreme Gradient Boosting multiclassification model was constructed to distinguish the three groups. SHapley Additive exPlanations (SHAP) analysis was performed to evaluate feature importance and interpret the model.

Results: Seven NVC features showed significant differences among the groups. The model achieved macro area under the curve values of 0.96 and 0.80 in the training and test sets, respectively. SHAP analysis identified papilla shape, red blood cell aggregation, number of capillary loops, number of crossed capillary loops and subpapillary venous plexus (SVP) as key features among the groups. Each group was characterised by specific NVC patterns. In Ctr, papilla shape emerged as the key feature and showed correlations with neutrophils, white blood cells and monocytes. In patients with RA, the number of crossed capillary loops was the most prominent feature and correlated with erythrocyte sedimentation rate, complement levels (C3 and C4) and inversely with immunoglobulin G. In patients with SLE, the SVP was the dominant feature and effectively distinguished SLE from both Ctr and RA.

Conclusions: This study developed a robust multiclassification model for differentiating autoimmune diseases using NVC features. The findings enhance our understanding of microvascular alterations and provide a potential tool for clinical diagnosis and disease monitoring.

Background: We aimed to assess the impact of socioeconomic status (SES) on risk of Sjögren's disease (SjD) compared with non-Sjögren's Sicca and population controls, and on the clinical features of SjD.

Methods: A single-centre UK cohort provided participants with SjD (European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) 2016, n=256) and non-Sjögren's Sicca (anti-Sjögren's syndrome type A (SSA)/Ro negative, n=175). Health Survey for England 2019 provided local population controls (n=972). English Indices of Multiple Deprivation (IMD) 2019 quintiles at recruitment and highest educational attainment defined SES.Adjusted logistic regression models evaluated associations between SES and diagnosis. Linear models assessed the impact of IMD on disease variables. Population controls were matched with age, sex and ethnicity to compare SES distributions.

Results: Across IMD and educational attainment, participants with SjD had lower SES status compared to Sicca (p=0.008 and p=0.018). Odds of SjD (vs Sicca) were highest in most deprived IMD quintile 1 and reduced by 74% in quintile 2 (OR 0.26 (0.12, 0.58), p<0.001).Immunoglobulin G and A levels were inversely associated with IMD. In SjD, each unit increase in IMD reduced IgG by 6.03% (-9.84%, -2.05%; p=0.003) and IgA by 6.46% (-10.87%, -1.60%; p=0.010).When compared with population controls, IMD was not a risk factor for SjD (p=0.257) whereas Sicca was associated with lower deprivation (p=0.003). Those with a degree level qualification had the highest odds of diagnosis (SjD or Sicca).

Conclusions: Low SES is associated with increased risk of SjD compared to Sicca and with higher immunoglobulin levels. The Sicca cohort may be less deprived than the general population. The role of environmental factors in modulating salivary gland pathology requires further exploration.