RMD Open最新文献

Objective: A panel of antibodies against three antigens, University Hasselt (UH)-rheumatoid arthritis (RA).305, 318 and 329, has been associated with lack of response to first-line therapy in the Care in early RA trial. This study aimed to determine the association of this antibody panel with first-line therapy response in an independent cohort.

Methods: Anti-UH-RA.305/318/329 antibody reactivity was determined using ELISA in 165 baseline samples of the CAP48 cohort, an observational cohort of patients with early and naïve RA treated mainly with methotrexate monotherapy. Multivariable analyses assessed associations between baseline antibody reactivity and failure to reach remission or low disease activity (LDA) at 3, 6, 9 and 24 months according to the Disease Activity Score 28-joint C-reactive protein (DAS28CRP) and clinical/simplified disease activity index (SDAI).

Results: In the total RA cohort, baseline anti-UH-RA.305/318/329 antibody reactivity was significantly higher in patients not achieving LDA versus those achieving LDA at 9 months (31.6% vs 11.3% for DAS28CRP/SDAI; OR 3.64, 95% CI 1.34 to 9.91, p=0.045). In patients with seronegative RA, a significant association between antibody reactivity and not achieving LDA based on DAS28CRP (42.1% vs 12.5%; OR 5.09, 95% CI 1.2 to 27.0, p=0.05) was already observed at 6 months. After 24 months, baseline antibody positivity remained significantly associated with not achieving LDA based on SDAI (OR 29.9, 95% CI 2.5 to 109.2, p=0.01) in patients with seronegative status.

Discussion: In the CAP48 cohort, the anti-UH-RA antibody panel was associated with a lack of response to first-line therapy for certain clinical measures, observed at 9 months in the total RA cohort and at 6 and 24 months in patients with seronegative status. The antibody panel should be further validated for its use in early personalised RA treatment.

Objective: To assess all-cause mortality in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and to examine the influence of sex, comorbidities and biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in a large, multinational, real-world cohort.

Methods: This retrospective cohort study used the TriNetX Global Collaborative Network, comprising anonymised electronic health records from over 150 million individuals across >100 healthcare organisations worldwide. Adults with ≥2 diagnoses of ankylosing spondylitis or arthropathic psoriasis between 2010 and 2020 were included. Propensity score matching accounted for demographics and comorbidities. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate HRs for all-cause mortality, comparing axSpA and PsA cohorts with each other and with matched general population controls.

Results: We identified 32 368 patients with axSpA, 52 402 patients with PsA and 9 742 949 controls. Compared with the general population, mortality risk was significantly higher in axSpA (HR 1.71, 95% CI 1.61 to 1.81) and PsA (HR 1.26, 95% CI 1.20 to 1.32). Mortality was 42% greater in axSpA than PsA (HR 1.42, 95% CI 1.34 to 1.51). Male sex was associated with increased mortality (axSpA HR 1.65; PsA HR 1.26). Treatment with b/tsDMARDs, particularly tumour necrosis factor (TNF) inhibitors, reduced mortality by 47% in axSpA and 38% in PsA compared with untreated patients.

Conclusion: All-cause mortality remains elevated in axSpA and PsA, particularly in axSpA. Male sex predicts poorer survival, whereas TNF inhibitor therapy is associated with improved outcomes. Early, targeted management may help reduce mortality in spondyloarthritis.

Objective: This study aimed to evaluate the prevalence of hyposplenism in patients with systemic lupus erythematosus (SLE) and its association with an increased risk of infection.

Methods: This single-centre study included patients with SLE who underwent a systematic evaluation for Howell-Jolly bodies (HJB) on peripheral blood smear, a marker of hyposplenism. Patients exhibiting HJB were classified as having hyposplenism (cases), whereas those without such inclusions were considered to have normal splenic function (controls). We collected radiological data to assess spleen morphology. The prevalence of infections and thrombosis was recorded.

Results: In a tertiary care cohort of 245 patients, 23 (9.4%) demonstrated HJB on peripheral smear, after exclusion of those with a history of splenectomy or intrinsic haemolytic anaemia. In multivariable analysis, three factors were independently associated with hyposplenism: paediatric-onset SLE (OR 5.2, 95% CI 1.3 to 21.2, p=0.02), antiphospholipid syndrome (OR 6.8, 95% CI 2.2 to 20.8, p=0.001) and history of constitutional symptoms of SLE (OR 3.9, 95% CI 1.2 to 12.4, p=0.02). Patients with HJB had a higher risk of infection-related hospitalisation (OR 7.3, 95% CI 2.4 to 21.8, p<0.001), particularly pneumococcal infections (5/23 cases (21.7%) vs 1/222 controls (0.5%), p<0.001), but no increased risk of thrombosis (OR 1.6, 95% CI 0.3 to 7.8, p=0.57). Hyposplenism was associated with splenic hypoplasia identified on abdominal CT scan (6/23 assessed cases (26%) vs 0/166 assessed controls (0%), p<0.001), but not with splenic calcifications. Hyposplenism was also associated with eosinophilia, neutrophilia, monocytosis and thrombocytosis.

Conclusion: Hyposplenism was observed in 9.4% of patients with SLE in a tertiary care cohort and was significantly associated with an increased risk of infection and radiological splenic hypoplasia. These findings highlight the importance of preventive measures for impaired splenic function, including patient and physician education, vaccination and infection surveillance in this population.

Background: This study aimed to explore the association of the sarcopenia questionnaire Strength, Assistance with walking, Rise from a chair, Climb stairs, Falls (SARC-F) with muscle strength, physical performance, daily activity, patient-reported outcomes (PROs) and body composition in patients with axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA).

Methods: In this cross-sectional study, patient and disease characteristics including physical function, performance measures and body composition assessed by dual-energy X-ray absorptiometry (DXA) were analysed. Variables were compared between patients with a SARC-F score ≥4 and <4, higher versus lower sarcopenia risk. Linear regression examined associations, adjusted for age and sex.

Results: Overall, 54 of 213 patients with SpA (65.7% axSpA, 34.3% PsA) had a SARC-F score ≥4 (24.4%). DXA identified sarcopenia and sarcopenic obesity in 4 patients each (7.7%). Patients with SARC-F scores ≥4 were older, predominantly female or obese, had longer disease duration, higher disease activity, lower physical performance, decreased muscle strength and daily activity and more unfavourable body composition. Total SARC-F score was consistently associated with muscle strength, physical performance, PROs and DXA components. Higher body mass index and patient global assessment were independently associated with higher SARC-F scores. The SARC-F ≥4 threshold showed moderate specificity (76%) but low sensitivity (50%) for DXA-defined sarcopenia, with a high negative predictive value (97%).

Conclusions: SARC-F was significantly associated with disease activity, muscle strength and physical performance, but showed limited ability to identify DXA-defined sarcopenia. Further research is needed to clarify its clinical utility for risk stratification in rheumatic diseases.

Neuropathic pain is a devastating type of pain that significantly reduces the quality of life of affected people. Traditionally considered as mechanistically distinct from pain induced by classical inflammatory states, studies continue to reveal more commonalities than differences, with a whole host of pathological changes in the environment of local peripheral nerves accompanying chronic neuropathic pain conditions. This narrative review provides an overview of the cellular and molecular drivers of neuropathic pain, highlighting some of the seminal publications from past and present. We discuss both neuronal and non-neuronal mechanisms contributing to neuropathic pain (eg, immune and stromal cell dysregulation). Particular attention is given to studies involving human cohorts which, until recently, have been less common in the field, due to the difficulties in accessing relevant tissues, like nervous system samples. The consequences of recent findings for analgesic drug development are also discussed, both in the context of neuropathic and non-neuropathic pain.

Objective: To present updated integrated safety analyses of bimekizumab in patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA).

Methods: Safety data pooled from six phase IIb/III studies in axSpA and PsA (data-cut: July 2023 for phase III) reported for patients who received ≥1 dose of bimekizumab 160 mg every 4 weeks. Treatment-emergent adverse events (TEAEs) were reported using exposure-adjusted incidence rate per 100 patient-years (EAIR/100 PY).

Results: 848 patients with axSpA (total exposure: 2513.8 PY) and 1409 patients with PsA (3655.9 PY) were included. TEAE incidence (EAIR/100 PY) was 129.6 in axSpA and 126.9 in PsA. Study discontinuations due to TEAEs were infrequent (EAIR/100 PY for axSpA: 2.4; PsA: 2.9). The most frequent TEAEs were SARS-CoV-2 (COVID-19) infection (EAIR/100 PY for axSpA: 9.9; PsA: 9.9), nasopharyngitis (EAIR/100 PY for axSpA: 8.4; PsA: 6.8) and upper respiratory tract infection (EAIR/100 PY for axSpA: 5.0; PsA: 5.7). EAIR/100 PY for oral candidiasis was 3.5 in axSpA and 3.8 in PsA; most cases were mild/moderate, with few leading to study discontinuation (EAIR/100 PY for axSpA: 0.2; PsA: 0.3). Serious opportunistic infections were infrequent (EAIR/100 PY for axSpA: 0; PsA: 0.1), with no active tuberculosis. EAIR/100 PY for hepatic events was 5.3 in axSpA and 5.0 in PsA. EAIRs for adjudicated definite/probable inflammatory bowel disease, uveitis, adjudicated major adverse cardiovascular events and adjudicated suicidal ideation/behaviour were low.

Conclusion: TEAE EAIRs were similar between axSpA and PsA. Bimekizumab demonstrated tolerability up to 5 years (2 years in phase III); no new safety signals were identified.

Trial registration numbers: NCT02963506; NCT03355573; NCT03928704; NCT03928743; NCT04436640; NCT02969525; NCT03347110; NCT03895203; NCT03896581; NCT04009499.

Objectives: To describe diagnostic framework classification, treatment patterns and outcomes in Kawasaki disease-associated macrophage activation syndrome (KD-MAS) using a single-centre cohort and a structured descriptive synthesis of published cases to inform hypothesis generation and future refinement of diagnostic and management strategies for KD-MAS.

Methods: We performed a retrospective single-centre cohort study. MAS was classified by haemophagocytic lymphohistiocytosis (HLH)-2004, HLH-2009 or 2016 systemic juvenile idiopathic arthritis (sJIA)-MAS criteria. Data were abstracted around a prespecified MAS window; severity was indexed by haemophagocytic syndrome diagnostic score (HScore) and the association between HScore and treatment escalation was assessed using Firth's logistic regression. In parallel, we conducted a literature review.

Results: In our centre, incidence was 0.6% (22/3786); mean age was 3.72 years; coronary involvement was 77.2%. The proportions of clinician-diagnosed KD-MAS cases fulfilling each framework were HLH-2004 14/22, HLH-2009 18/22 and 2016 sJIA-MAS 20/22; 11 met all three. Cytopenias, liver dysfunction and coagulopathy were frequent; management followed stepwise escalation from intravenous immunoglobulin (IVIG) or corticosteroid monotherapy to IVIG plus corticosteroids and, when required, to adjunct immunosuppressive/biologic therapy; similar patterns appeared in the literature. HScore was higher with intensified therapy than with standard therapy (median 274 vs 199; p=0.020). Each 10-point HScore increase was associated with higher odds of escalation (OR 1.44 univariable; 1.37 adjusted).

Conclusion: The 2016 sJIA-MAS criteria demonstrate the highest proportion fulfilling criteria in our cohort for KD-MAS. Treatment in our cohort and in published cases generally reflected a stepwise, typically progressing from IVIG±glucocorticoids to adjunct immunosuppressants/biologics. Higher HScores co-occurred with escalation, suggesting they capture baseline severity; prospective multicentre studies are needed to test incremental value and risk-stratification thresholds.

Background: The Leiden group and the Assessment of Spondyloarthritis International Society (ASAS)-MRI study group have proposed definitions for structural (SL) and active (AL) lesions typical for axial spondyloarthritis (axSpA) on MRI of the sacroiliac joints (MRI-SIJ).

Objectives: To analyse the predictive validity of proposed SL and AL MRI-SIJ definitions in early axSpA and compare proposed AL with the current ASAS-MRI-SIJ+ definition.

Methods: Patients with chronic back pain (≤2 years) from the Spondyloarthritis Caught Early cohort were diagnosed as axSpA or non-axSpA after 2 years follow-up. Three central readers scored baseline MRI-SIJ for SL (erosions and fat lesions) and AL (bone marrow oedema). Validation required specificity and positive predictive value (PPV) ≥95%.

Results: Among 643 patients (52% axSpA), SL were infrequent (2%-14%). All Leiden and most MRI study group SL definitions met the validation threshold, except for 'erosion in ≥2 consecutive slices' and the overall MRI study group definition (PPV <95%). The ASAS-MRI-SIJ+ definition had a higher sensitivity than the MRI study group AL (40% vs 31%) with similar specificity (98% vs 99%). Combining SL and AL, the Leiden SL with ASAS-MRI-SIJ+ definition met the validation threshold with the highest sensitivity (46%). SL increased sensitivity beyond AL alone by 6%-11%.

Conclusions: The ASAS-MRI-SIJ+ definition outperforms the MRI study group AL. The Leiden SL combined with the ASAS-MRI-SIJ+ definition is validated, most sensitive and feasible as it simultaneously upholds lesion quantification and detection precision, making it the preferred approach. Nevertheless, SL were uncommon in early axSpA, contributing only marginally beyond AL definitions in early diagnosis.

Objectives: To develop response criteria for rheumatoid arthritis (RA) using the two-component Disease Activity Score in 28 joints (2C-DAS28).

Methods: Data were available for three stages of RA treatment progression, determined by the disease-modifying antirheumatic drug prescribed: early (on methotrexate; n=1051), established (on tumour necrosis factor inhibitors; n=989) and late RA (on second-line or later therapy; n=301). Inflammation response was defined as achieving remission or a clinically meaningful reduction in disease activity after 3 months of treatment. Corresponding 2C-DAS28 thresholds were determined using receiver operating characteristic analysis and Youden's J, based on Boolean V.2.0 remission and clinical disease activity index response. The correlation of the proposed criteria with synovial thickness (ST) and power Doppler (PD) was assessed in an independent cohort (n=161) and compared with conventional response criteria. Finally, 6-month disease activity was compared between 3-month 2C-DAS28 responders and non-responders.

Results: Thresholds to define inflammation response were 2C-DAS28<1.8 or a decrease in 2C-DAS28>1.7. In the validation cohort, 3-month 2C-DAS28 response was significantly correlated with lower ST (r=-0.25 (95% CI -0.47 to -0.04), p=0.037) and PD scores (r=-0.28 (95% CI -0.52 to -0.04), p=0.042). By contrast, conventional response criteria showed no significant correlation with synovitis scores. In the discovery cohorts, 3-month 2C-DAS28 responders retained lower disease activity at 6 months than non-responders.

Conclusion: 2C-DAS28 response correlates significantly with ultrasound-detected synovitis and is associated with improved clinical outcomes. This may support identification of biomarkers of treatment efficacy and clinical stratification, to identify patients with ongoing inflammation and those in whom disease activity is driven by non-inflammatory features.

Objectives: To compare the sensitivity of International Study Group (ISG, 1990), International Criteria for Behçet's Disease (ICBD, 2014) and the Paediatric Behçet's Disease (PEDBD, 2016) classification criteria in paediatric Behçet's disease (pBD) within an endemic cohort and to assess organ involvement, treatment patterns, outcomes and cumulative damage using the Behçet's Syndrome Overall Damage Index.

Methods: We retrospectively analysed 69 consecutive children with clinician-diagnosed pBD (symptom onset ≤18 years) at a tertiary centre in Türkiye (2020-2025). Classification criteria were applied at the last visit. The primary outcome was sensitivity versus clinician diagnosis; secondary outcomes included sex-stratified risks, therapies/adverse events and cumulative damage.

Results: ICBD classified 97.1% of cases, compared with 58.0% for ISG and 53.6% for PEDBD. Neurovascular involvement occurred in 18.8% (mainly cerebral venous thrombosis), vascular in 20.3% and ocular in 17.4% (posterior-segment 11.6%). Boys had higher risks of neurovascular disease, while girls more often had genital ulcers. Treatment followed steroid-sparing pathways (colchicine 98.6%, azathioprine 63.8%, antitumour necrosis factor 21.7%); adverse events occurred in 15.9% and non-adherence in 11.6%. Cumulative damage was low to moderate, with a mean BODI score of 0.45 (range 0-3).

Conclusions: In this endemic paediatric cohort, ICBD demonstrated superior sensitivity, while ISG and PEDBD classified only half of cases. Morbidity was driven by neurovascular events and, less frequently, posterior-segment ocular disease. Findings support an ICBD-anchored approach with co-reporting of ISG/PEDBD for comparability. Low-threshold neuro-ophthalmic evaluation and timely steroid-sparing escalation are critical for sight/central nervous system-threatening disease. Targeted vascular imaging and adherence-focused adolescent care remain priorities.