Objectives: To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by ⁶⁸gallium-labelled fibroblast activation protein inhibitor-04 (⁶⁸Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA). Methods: We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with ⁶⁸Ga-FAPI-04. ⁶⁸Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up. Results: 36 patients with psoriasis were enrolled. ⁶⁸Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between ⁶⁸Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal ⁶⁸Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings. Conclusions: Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.

Objective: Organ damage is a key determinant of poor prognosis and increased mortality in systemic lupus erythematosus (SLE). However, no validated clinical tools for predicting damage accumulation currently exist. We sought to develop a machine learning-based model to predict early organ damage in patients with SLE. Methods: Classification criteria (American College of Rheumatology (ACR)-1997, Systemic Lupus International Collaborating Clinics (SLICC)-2012, European League Against Rheumatism (EULAR)/ACR-2019) and non-criteria features of a cohort of 914 patients with SLE were analysed to predict damage (defined as SLICC/ACR Damage Index (SDI)) within 5 years since diagnosis. Feature selection and model construction were performed using the least absolute shrinkage and selection operator-logistic regression (LASSO-LR). The best model in 10-fold cross-validation was tested in an external cohort (n=50). Results: A LASSO-LR model incorporating 16 criteria and non-criteria features predicted early organ damage with area under the receiver operating characteristic curve (AUC) values of 0.80 (95% CI 0.74 to 0.87) and 0.86 (95% CI 0.76 to 0.97) in the derivation and external validation cohorts, respectively, outperforming the ACR-1997 (AUC 0.70; 95% CI 0.62 to 0.78), SLICC-2012 (AUC 0.74; 95% CI 0.66 to 0.81) and EULAR/ACR-2019 (AUC 0.70; 95% CI 0.63 to 0.78) classification systems. Features most strongly associated with damage included the SLICC-2012 neurological disorder, EULAR/ACR-2019 class III/IV lupus nephritis and among non-criteria manifestations, myocarditis and interstitial lung disease. Operating the model as a binary classifier (early damage versus no damage), it demonstrated high specificity (0.90, 95% CI 0.78 to 0.95). The model can be converted to a simplified scoring system, with a threshold of ≥3 achieving an AUC of 0.86 (95% CI 0.75 to 0.96). Conclusion: We developed and validated a clinician-friendly model for early organ damage prediction in SLE, facilitating risk stratification.

Objective: Patients with systemic lupus erythematosus (SLE) require long-term treatment and experience reduced quality of life (QOL). CD19 chimeric antigen receptor (CAR) T cell therapy can achieve sustained drug-free remission in patients with SLE. The impact of CAR T cell therapy on QOL and direct healthcare costs has not been evaluated. Here, we analyzed longitudinal QOL before and after CAR T cell therapy and performed an assessment of direct healthcare costs. Methods: Physical and mental health were assessed using the standardized 36-item Short Form Health Survey before and 1 year after treatment. Annual direct healthcare costs were analyzed based on inpatient admissions, emergency department visits, outpatient visits, and prescription drug costs in the German healthcare service. Results: A preliminary analysis was conducted on 8 patients with SLE (7 female, 1 male; age range 19-38 years) who received CAR T cell therapy and who were followed for > 2 years. CAR T cell therapy resulted in improvement in the QOL in all patients. The most notable improvement was observed in physical health (from 22.4% to 75.5%), although mental health also improved (from 24.7% to 63%). QOL values rose to the level of a healthy comparison cohort. Additionally, CAR T cell therapy led to a substantial decrease in annual direct healthcare costs from €29,672/year (US $34,353/year) to €3094/year ($3582/year) after treatment. Conclusion: In addition to clinical efficacy, in this preliminary cohort, CD19 CAR T cell treatment improves QOL in patients with SLE and may substantially reduce the direct socioeconomic burden associated with active disease by > 90%.

Background: The accruing evidence about the efficacy of anti-IL-1 agents in Familial Mediterranean Fever (FMF) patients led to their widespread off-label use. Therefore, identifying precise indications and clinical characteristics of IL-1i-warranting patients are important. This study investigated the clinical characteristics and treatment indications of patients with FMF requiring interleukin 1 inhibition therapy (IL-1i). Methods: Hospital records of FMF patients attending a tertiary care center at the Department of Rheumatology, University of Health Sciences, Basaksehir Cam and Sakura City Hospital were retrospectively analyzed. Data on symptoms and disease manifestations, age of symptom onset, time to diagnosis, MEFV variants, type of treatment, and their indications were collected. Results: Between June 2020 and March 2023, 312 FMF patients were identified. The mean age at the onset of symptoms was 14.0, and the mean time to diagnosis was 11.9 years. In total, 87.1% of patients were receiving colchicine monotherapy, while the remaining 11.8% warranted IL-1i. Clinical symptoms and flare manifestations did not show a significant difference between the two groups. However, patients receiving IL-1i started having symptoms at younger age (11.5 vs. 14.5, p = 0.042) and time to diagnosis was longer (18.2 vs. 11.0, p < 0.01). M694V homozygosity was more common in patients receiving IL-1i. Indications for patients receiving IL-1i were colchicine resistance (8.0%), secondary amyloidosis (5.1%), and colchicine intolerance (2.2%). Conclusions: This study shows that a subset of FMF patients, particularly those with a more severe phenotype with an earlier disease onset and M694V homozygosity, require IL-1i treatment despite the overall good efficacy and tolerability of colchicine, primarily due to colchicine resistance, intolerance, or complications such as amyloidosis.

Dear Editor, The development of effective screening strategies for psoriatic arthritis (PsA) is a challenge yet to be overcome. Established screening questionnaires are widely used for their high sensitivity but result in a high numbers of patients who are unnecessarily referred to rheumatologists due to their fairly poor specificity [ 1]. Grobelski et al. recently showed that the use of handheld ultrasound devices by dermatologists can improve the specificity of a PsA assessment [ 2]. To further improve and standardize early diagnosis of PsA, EULAR published new ‘points to consider’ recommending classifying any patients with psoriasis (PsO) and arthralgias as ‘subclinical PsA’ [ 3]. These advancements could potentially revolutionize screening for PsA. In accordance with this notion, we performed a cross-sectional study, in which experienced dermatologists screened 40 PsO patients attending a day care unit (Nürnberg) for intensified local therapy ( Supplementary Table S1, available at Rheumatology online). The dermatologists were given a training on entheseal ultrasound by an experienced rheumatologist (A.J.H., >10 years of experience) using a VSCAN air handheld ultrasound device (GE Healthcare, Solingen, Germany; frequency range 3–12 MHz). Data collection took place from October 2022 to June 2023. This study was approved by the ethics committee (no. 56_21 B) of the University of Erlangen-Nuremberg (FAU). All patients signed written informed consent before study participation.

Background: Janus kinase inhibitors (JAKi), like baricitinib, are used as monotherapy (MONO) and in combination with methotrexate (MTX) in rheumatoid arthritis (RA) patients. This study aimed to evaluate the long-term efficacy, drug survival and safety of baricitinib MONO versus combination therapy (COMBO) in a prospective cohort of patients with RA. Methods: We analysed data from 219 RA patients initiating baricitinib in a single-centre, prospective observational cohort between 2017 and 2023. Clinical data, patient-reported outcomes and safety events were collected every 3 months. Drug survival was analysed using the Kaplan-Meier method, and longitudinal outcomes were assessed using linear mixed-effects models. Results: The cohort included 219 patients (165 MONO, 54 COMBO) with high baseline disease activity (mean DAS28-ESR 4.0). Both groups showed rapid and sustained clinical improvement, with disease activity stabilising in the low range by 6 months of treatment. One third of the patients (n=72, 33%) achieved Boolean remission, with no significant difference between groups (p=0.35). Median drug survival was 36 months and was similar for both regimens (log-rank p=0.82). Discontinuation due to adverse events occurred in 10.9% of patients. Four thrombotic events were noted, all in patients with pre-existing cardiovascular risk factors, with no new safety signals emerging. Conclusions: In this real-world cohort, baricitinib demonstrated sustained long-term effectiveness, drug survival and an acceptable safety profile. The similar outcomes observed for MONO and COMBO indicate that baricitinib may be used effectively as MONO in patients with RA for whom MTX is not suitable or tolerated.