Objectives This study aimed to compare treatment outcomes following initiation of a first tumour necrosis factor inhibitor (TNFi) between patients with axial spondyloarthritis (axSpA) who fulfil the revised Assessment of SpondyloArthritis international Society - Spondyloarthritis Research and Treatment Network (ASAS-SPARTAN) 2025 classification criteria for axSpA and those who do not, within a population meeting the ASAS 2009 classification criteria.Methods We included 1195 patients with axSpA fulfilling the ASAS 2009 classification criteria from the Swiss Clinical Quality Management in Rheumatic Diseases registry who initiated a first TNFi. Patients were stratified according to fulfilment of the revised ASAS-SPARTAN 2025 axSpA classification criteria (863 fulfilling vs 332 not fulfilling the revised criteria). Drug survival was analysed using multivariable Cox proportional hazards models adjusted for age and sex. Multivariable logistic regression models were used to compare the odds of achieving an Axial Spondyloarthritis Disease Activity Score (ASDAS) <2.1 at 1 year.Results Patients who did not fulfil the revised criteria were more frequently female, more often human leucocyte antigen B27 negative and had fewer objective imaging findings indicative of axSpA. The frequency of non-axial manifestations, as well as measures of disease activity, functional impairment and spinal mobility, were comparable between the two groups. Patients fulfilling the revised criteria demonstrated longer TNFi retention (HR for drug discontinuation 0.79, 95% CI 0.68 to 0.93) and a higher ASDAS <2.1 response rate (OR 1.79, 95% CI 1.27 to 2.55).Conclusions Fulfilment of the ASAS-SPARTAN 2025 classification criteria for axSpA is associated with a longer TNFi retention and an improved treatment response.
Objective Syndrome of undifferentiated recurrent fever (SURF) is a new entity among non-hereditary periodic fever syndromes. Using a complex approach, we looked at clinical and laboratory profiles of the well-known syndrome of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) and patients with SURF during febrile and afebrile conditions searching for clinically meaningful differences.Methods Patients were prospectively enrolled and their symptoms recorded. Genetic analysis was part of the diagnostic process. Blood samples collected at specific times (febrile/afebrile) were compared with febrile and healthy controls for standard parameters (C-reactive protein (CRP), serum amyloid A, procalcitonin), S100A8/A9 and S100A12 proteins, and 48 mediators via Bio-Plex analysis, followed by ELISA confirmation.Results A total of 94 patients and 35 controls were recruited. Rash and diarrhoea, arthralgia, myalgia and abdominalgia were more frequent with longer fever duration in patients with SURF than with PFAPA, in whom significantly (p<0.001) better response to episodic prednisone was recorded. In febrile samples, inflammatory parameters or cytokines did not differ between groups apart from CRP being higher in periodic fever than controls. In an afebrile sample of patients with periodic fever, 11 proinflammatory cytokines were significantly higher than in healthy controls. Afebrile SURF and PFAPA differed significantly (p<0.05), with nine mediators higher and one lower in SURF.Conclusion Analysis of routine and experimental biomarkers revealed heterogeneous immune dysregulation. Elevation of several inflammatory mediators in afebrile sample of patients with periodic fever indicates subclinical inflammation with granulocyte colony-stimulating factor and interleukin-18 notably higher in SURF than in PFAPA. Our data provide new insights into the immune mechanisms of non-hereditary periodic fever syndromes and support further biomarker-driven research.
Objective Giant cell arteritis (GCA) is a systemic vasculitis associated with severe ischaemic complications. Despite recognised sex differences in disease susceptibility and clinical presentation, the molecular mechanisms underlying these variations remain unclear.Methods We performed a transcriptome-wide association study to identify sex-associated transcriptional profiles in CD14+ monocytes and CD4+ T cells from 18 treatment-naive patients with GCA and 31 controls.Results Differential expression revealed marked transcriptional alterations in female patients with GCA compared with healthy women, particularly in CD4+ T cells, whereas no differentially expressed genes (DEGs) were identified in male patients compared with healthy men. Most DEGs also significantly differed between female and male patients. Specifically, CD4+ T cells of female patients showed transcriptional reprogramming characterised by upregulation of genes involved in vascular interaction and tissue homing (FLT1, NOTCH1, FURIN, CLDN5 and MYL9) and downregulation of cytotoxic/Th1 effector-related genes (TBX21, EOMES, CX3CR1, KLRF1, CCL5 and CCL4), consistent with enhanced vascular engagement and redistribution of effector programmes. Monocytes from female patients showed differential expression of key genes, including downregulation of NR4A1, a regulator of differentiation of vascular surveillance monocytes, and upregulation of ADAMTS2, involved in extracellular matrix remodelling.Conclusion These findings reveal sex-specific transcriptional landscapes in GCA, with female patients exhibiting CD4+ T cell reprogramming towards vascular engagement and dysregulation of monocyte genes with vascular relevance. These sex-dimorphic signatures provide a mechanistic basis for sex differences in GCA and highlight the value of sex-stratified approaches for improved patient management.
Background Interstitial lung disease (ILD) is a major determinant of morbidity and mortality in systemic sclerosis (SSc). Automated quantitative CT (qCT) enables reproducible assessment of ILD extent and parenchymal texture composition. Whether circulating biomarkers reflect distinct qCT-defined features of SSc-ILD remains insufficiently characterised.Objectives To determine whether circulating biomarkers are associated with ILD presence, qCT-derived disease burden and radiological pattern composition in patients with SSc.Methods In this cross-sectional study, consecutive patients with SSc underwent same-day serum sampling and high-resolution CT. ILD presence was assessed visually, while qCT quantified ground-glass opacities (GGO), fibrotic abnormalities and total ILD extent (%). Serum levels of Krebs von den Lungen-6 (KL-6), C-C motif chemokine ligand 18 (CCL-18), surfactant protein D (SP-D), interleukin (IL)-33, IL-11, IL-25 and matrix metalloproteinase 12 (MMP-12) were measured using commercial ELISA assays.Results Eighty-two patients were included; 59 (72%) had ILD on CT. KL-6, CCL-18 and SP-D levels were significantly higher in patients with ILD, with KL-6 remaining independently associated with ILD presence in multivariable analysis. KL-6 showed the strongest associations with qCT measures of disease burden, including total ILD extent, GGO and fibrotic abnormalities. CCL-18 was associated with total ILD extent and GGO. SP-D was linked to ILD presence but not to qCT-derived measures of disease burden. IL-25 showed a preliminary association with the GGO-to-fibrosis ratio and was higher in patients with a GGO-predominant qCT pattern. IL-33, IL-11 and MMP-12 did not show significant associations with ILD presence or qCT-derived lung involvement.Conclusions Circulating biomarkers showed distinct associations with SSc-ILD presence and qCT-defined disease burden. IL-25 may also reflect radiological pattern composition, warranting validation in independent cohorts.
Objective To evaluate the discriminatory performance of shear wave elastography (SWE) for detecting ultrasound-confirmed wrist synovitis in rheumatoid arthritis (RA), derive preliminary diagnostic cut-offs and examine associations between synovial stiffness and ultrasound inflammatory burden.Methods This cross-sectional pilot study included 133 participants: 60 patients with RA and ultrasound-confirmed synovitis, 30 patients with RA without ultrasound-confirmed synovitis, 30 healthy controls and 13 individuals with wrist ganglia. Bilateral radiocarpal and midcarpal recesses were assessed using B-mode ultrasound, power Doppler (PD) and SWE. Ultrasound-confirmed synovitis was prespecified as synovial hypertrophy (SH) grade ≥2, irrespective of PD. Associations between SWE and ultrasound inflammatory burden were assessed using recess-level linear mixed-effects models and participant-level analyses.Results Participant-level mean SWE showed high discriminatory performance within this pilot cohort for ultrasound-confirmed synovitis: area under the curve (AUC) 0.998 for kPa, with an optimal cut-off of 19.49 kPa (98.3% sensitivity; 100% specificity) and AUC 0.994 for m/s, with an optimal cut-off of 2.89 m/s (95.0% sensitivity; 100% specificity). Mean SWE was significantly higher in patients with ultrasound-confirmed synovitis than in all other groups (p<0.001). At the recess level, SWE increased progressively with wrist-adapted Global Outcome Measures in Rheumatology (OMERACT)-European Alliance of Associations for Rheumatology (EULAR) Synovitis Score, SH and PD grades (all p<0.001). After adjustment for Disease Activity Score in 28 joints using erythrocyte sedimentation rate, age, disease duration, current conventional synthetic disease-modifying antirheumatic drug use and current biologic disease-modifying antirheumatic drug use, wrist-adapted GLOESS mean and PD mean were independently associated with SWE.Conclusion SWE showed high discriminatory performance for ultrasound-confirmed synovitis within this single-operator pilot cohort and was closely associated with ultrasound inflammatory burden. The preliminary diagnostic cut-offs require independent validation, including assessment of interobserver reproducibility, before clinical implementation.
