RMD Open最新文献

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.

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.