RMD Open最新文献

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.

Background: Remission and low-disease activity are recommended targets in systemic lupus erythematosus (SLE), yet many patients fail to achieve them, underscoring the need to identify contributing barriers. We explored whether comorbidities-some of which share genetic risk with lupus-and their specific patterns influence target accomplishment.

Methods: Retrospective cohort of 347 patients with active SLE receiving treatment intensification at inclusion. Comorbidities (n=140), disease activity, treatments and organ damage were monitored (median follow-up 5 years). Mixed-effects assessed relationships between comorbidities and definitions of remission in SLE/lupus low disease activity state (DORIS/LLDAS). Random forests ranked comorbidities according to the strength of associations.

Results: Despite the relatively young age (median 46 years) and short disease duration (median 9 months), patients with SLE exhibited high comorbidity burden (comorbidities count, Rheumatic Disease Comorbidity Index, Elixhauser, Charlson), which increased longitudinally and was associated with reduced attainment of DORIS (ORs: 0.77-0.87, p<0.05) and LLDAS (ORs: 0.74-0.91, p<0.01). Obesity, dyslipidaemia, hypertension, stroke, depression, fibromyalgia and thyroid disorders emerged as the most influential. Presence of ≥1 of these conditions (n=238 [68.6%]) was linked to 55-60% lower likelihood of durable DORIS/LLDAS (≥50% time). Marginal structural models (MSMs) confirmed an independent comorbidities-targets association, regardless of prior achievement, explained by smouldering activity and delayed glucocorticoid tapering. While immunosuppressant/biologic use was comparable, comorbid patients received lower glucocorticoid doses during high disease activity. Comorbidities were also associated with greater damage accrual (IRR: 1.38, 95% CI 1.11 to 1.71), attenuated in patients with sustained DORIS/LLDAS.

Conclusions: Patients with SLE manifest high comorbidity burden, with distinct patterns linked to reduced target attainment. In these patients, vigilant monitoring and treatment adjustments are essential to sustain disease control and prevent damage.

Objective: To describe the clinical, biological and genetic characteristics of paediatric-onset A20 haploinsufficiency (HA20) and to identify key clinical features that may guide early diagnosis and management.

Methods: Multicentre, retrospective observational cohort study through the French national paediatric rheumatology network and national reference laboratories for genetic autoinflammatory diseases. 17 patients from 11 unrelated families, with disease onset before 18 years of age and carrying a tumour necrosis factor alpha-induced protein 3 (TNFAIP3) mutation, were included.

Results: Median age at symptom onset was 3 years (range: 1 month-17 years) with a median diagnostic delay of 9.7 years (range: 1-43 years). Boys had a significantly earlier onset and diagnosis than girls. The most common initial manifestations were oral ulcers (64.7%), fever (64.7%), abdominal pain (47.1%), arthralgia (35.3%) and skin eruption (17.6%). Genital ulcers occurred in 17.6% at onset but in 52.9% during follow-up. Gastrointestinal involvement was frequent (abdominal pain in 76.5% of patients and colitis in 35.3%). Other features included arthralgia (52.9%), arthritis (29.4%), skin eruption (41.2%), lymphadenopathy (35.3%), hepatomegaly (11.8%), headache (17.6%) and uveitis (5.9%). C reactive protein (CRP) levels were significantly higher during flares. Three novel TNFAIP3 variants were identified. Colchicine was effective as monotherapy in 40%. TNF-inhibitors showed the highest efficacy (adalimumab 60%, infliximab 100%).

Conclusions: HA20 should be suspected in children with fever and gastrointestinal inflammation, even in the absence of oral/genital ulcers. Early onset colitis, the distinctive morphology of mucosal ulcers and a positive family history for HA20 are particularly suggestive. Early genetic testing may enable prompt diagnosis and targeted therapy.

Objective: To evaluate the long-term efficacy of interleukin (IL)-17A inhibition with secukinumab on structural bone changes and clinical outcomes in psoriatic arthritis (PsA).

Methods: We conducted a phase-IV non-interventional study on adult patients with active PsA using high-resolution peripheral quantitative CT (HR-pQCT) and MRI of the hand over 48 months. All participants received secukinumab treatment and were followed up according to clinical practice, with repeated HR-pQCT and MRI. Number and volume of erosions, bone density, cortical and trabecular microarchitecture and bone biomechanical properties were assessed based on HR-pQCT scans. MRI synovitis, tenosynovitis, osteitis, periarticular inflammation, erosions and osteoproliferation were quantified by Psoriatic Arthritis MRI Score (PsAMRIS)-Outcome Measures in Rheumatology (OMERACT) score. Study outcomes included drug survival and changes from baseline in disease activity, functional status and imaging-detected inflammation and damage.

Results: 32 patients with PsA (40.6% female, mean age 56±7.5 years) were enrolled. Drug survival rate was 68.8% at 48 months. Secukinumab was highly effective in all PsA disease domains, with significant improvements in Disease Activity Score 28 (p<0.001), Leeds Enthesitis Index (p=0.027), Psoriasis Area and Severity Index (p=0.001), C reactive protein (p=0.09), Psoriatic Arthritis Impact of Disease (p<0.001) and pain (p<0.001). Functional status measured by the Health Assessment Questionnaire remained stable. On HR-pQCT, bone density, microarchitecture and biomechanics were preserved. There was no progression of bone erosions (all changes were not significant). On MRI, PsAMRIS erosion and osteoproliferation subitems increased marginally (+1.4 and +0.8, respectively), while inflammatory changes remained stably low. No major safety signals emerged.

Conclusion: Multimodal imaging with HR-pQCT and MRI showed no relevant progression of structural bone damage over 48 months in patients with PsA treated with secukinumab, suggesting that anti-IL-17A therapy induces sustained osteoprotective effects in PsA.

Background: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease with multifactorial pathogenesis. Although polygenic risk scores (PRSs) have been developed to enable early prediction, their accuracy remains limited. To address this limitation, we constructed a meta-polygenic risk score (metaPRS) integrating genetic markers associated with multiple SLE-associated traits.

Methods: 14 SLE-associated traits were identified through literature review, and trait-level PRSs were constructed based on the largest available East Asian genome-wide association studies datasets using SNP genotyping data of 2388 patients and 1132 controls from our own cohort. Significant trait-PRSs were integrated into a metaPRS using elastic net regression, which was further evaluated for disease prediction, risk stratification and clinical manifestation correlation, with internal validation via bootstrapping.

Results: Five trait-level PRSs were significantly associated with SLE in East Asian population: SLE development, smoking initiation, serum selenium levels, endometriosis and Graves' disease. The metaPRS merged from these five traits exhibited robust predictive performance (OR=2.12, area under the receiver operating characteristic curve (AUC)=0.69) and risk stratification (high risk vs low risk: OR=4.93, p<2e-16). Compared with the conventional PRS based solely on SLE risk genetic variants, the metaPRS achieved a 4.43% increase in OR and exhibited a statistically significant improvement in diagnostic discrimination, as measured by the AUC (p=0.046). Furthermore, metaPRS was associated with positivity for multiple autoantibodies and demonstrated better performance in childhood-onset SLE compared with adult-onset cases. Decomposition of the metaPRS revealed that both PRS_SLE and PRS_riskfactor contributed to SLE susceptibility, while clinical manifestations were exclusively driven by PRS_SLE.

Conclusions: We developed the first metaPRS of SLE by integrating genetic characteristics from multiple SLE-related risk factors, offering a new perspective for risk stratification and early diagnosis.

Objectives: Acute anterior ischaemic optic neuropathy (AION) is a feared ischaemic complication of giant cell arteritis (GCA). However, distinguishing arteritic AION (A-AION) from its non-arteritic counterpart (NA-AION), which accounts for approximately 90% of cases, can be challenging. Rapid initiation of glucocorticoids is essential to prevent irreversible vision loss in GCA but is unnecessary in NA-AION. This study evaluated the use of orbital MRI in differentiating A-AION from NA-AION.

Methods: In this prospective single-centre study, patients >50 years who had recent-onset AION were enrolled between June 2021 and October 2024. The final diagnosis of GCA was confirmed after comprehensive assessments and ≥6 months follow-up. Orbital MRIs were independently evaluated by two experienced radiologists blinded to the clinical diagnosis.

Results: Of the 18 patients analysed, nine had A-AION (two with bilateral involvement), while nine had NA-AION. MRI demonstrated differences between the groups, notably in contrast enhancement of the ophthalmic artery (72.7% vs 22.2%; p=0.07), perineural fat (90.9% vs 22.2%; p=0.005) and retrobulbar fat (100% vs 11.1%; p<0.001). The most discriminative MRI feature was retrobulbar fat enhancement, achieving 100% (95% CI 72 to 100) sensitivity and 89% (95% CI 52 to 100) specificity. Bilateral orbital enhancement was identified in more than half of the unaffected contralateral eyes in A-AION patients.

Conclusion: These results suggest that orbital MRI may help clinicians rapidly differentiate between A-AION and NA-AION to provide the most appropriate treatment.