OBJECTIVE:This study aimed to identify distinct clinical phenotypes within a Chinese cohort of patients with psoriatic arthritis (PsA). METHODS:A total of 1074 patient data were analyzed from the Chinese Psoriatic Arthritis Registry (CREPAR). A two-step clustering approach was used to identify patient subtypes based on the unsupervised clustering of baseline clinical characteristics. Kaplan-Meier curves were used to compare long-term remission probabilities across subtypes, and Cox proportional hazards regression models were used to identify independent risk factors. RESULTS:The cluster analysis identified three subtypes of patients with distinct clinical presentations, laboratory tests, and prognoses. Cluster 1 patients presented with the most extensive and intense polyarticular inflammation, accompanied by a 'concentrated-severe' pattern of dactylitis across multiple sites. Patients in Cluster 2 had the least peripheral joint involvement, with an extremely low incidence of dactylitis (0.8%). Cluster 3 is characterised by dactylitis in almost all patients (98.9%), presenting a extensive pattern with moderate frequency across sites, alongside common peripheral arthritis. A survival analysis revealed highly significant differences between subtypes in the probability curves for non-remission. Across all subtypes, the Cox regression identified the following independent risk factors: a later age at onset of arthritis, a longer duration of psoriasis, and high baseline DAPSA scores. CONCLUSION:The purpose of this study is to establish a clinical risk framework for Chinese PsA patients. Identification of high-risk patients based on specific joint/dactylitis patterns is crucial to guiding intensive treatment.

To evaluate the comparative value of traditional clinical features and novel immune-inflammatory indices in assessing disease activity in primary Sjögren's Disease (SjD), and to construct a robust classification model for moderate-to-severe disease activity using a machine learning approach. This cross-sectional study included 18,738 SjD patients from the Chinese Rheumatism Data Center (CRDC) multicenter prospective cohort. Spearman rank correlation and local polynomial regression (LOESS) were used to explore the relationship between systemic inflammatory indices and the EULAR Sjögren's syndrome disease activity index (ESSDAI). To identify moderate-to-severe disease activity (ESSDAI ≥ 5), data were randomly split into training and validation sets (7:3). Classification models were developed using various machine learning techniques. Higher ESSDAI scores were significantly associated with elevated levels of both traditional markers (ESR, CRP, IgG) and novel composite indices (NLR, CAR, CLR, IBI) (all p < 0.001). However, these indices exhibited only weak-to-moderate linear correlations with ESSDAI and displayed non-linear saturation trends. In multivariable logistic regression, traditional markers remained independent risk factors, whereas all novel composite indices lost statistical significance, yielding a poor validation area under the curve (AUC) of 0.678. Conversely, the XGBoost model demonstrated modestly favorable overall performance Feature importance analysis revealed that patient-reported outcomes, hemoglobin, WBC, age, and IgG were the top contributors to the model, while novel inflammatory indices were completely excluded. Novel immune-inflammatory indices lack provide no independent discriminative value for moderate-to-severe SjD activity when adjusted for traditional parameters. The XGBoost machine learning model effectively handles non-linear variables and highlights the core diagnostic importance of patient-reported outcomes (ESSPRI) and traditional clinical features, providing a favorable evaluation tool.

Background Patients with systemic lupus erythematosus (SLE) complicated by immune thrombocytopenia (SLE-ITP) exhibit an increased incidence of bleeding events and significantly reduced long-term survival, with poor responses to conventional therapies as well as biologic agents. Methods In an investigator-initiated, single-arm, dose-escalation trial, six patients with refractory SLE-ITP received anti-CD19 chimeric antigen receptor (CAR) T cells after lymphodepleting chemotherapy. The primary outcome was safety. Secondary outcomes included overall response rate at time points (complete remission [CR]: platelet count ≥ 100 × 109/L; partial remission [PR]: ≥30 × 109/L with 2-fold baseline increase). Findings All patients achieved clinical response (CR or PR)—with three attaining CR—and discontinued immunosuppressants, with a median follow-up of 12 months. Treatment-related adverse events were limited to grade 1 cytokine release syndrome in two patients, and no immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Continuously accumulating bone marrow plasma cells, overactivated bone marrow B cell signaling pathways, and weakened activity of the megakaryocyte maturation pathway, along with dysregulated transcription factors, were observed in three PR patients by exploratory single-cell multi-omics. Conclusion These results preliminarily support CD19 CAR T cell therapy as a promising and safe treatment for refractory SLE-ITP. Large-scale trials are needed to verify these conclusions (ClinicalTrials.gov: NCT05930314). Funding This study was supported by the Chinese National Key Technology R&D Program, Ministry of Science and Technology (2021YFC2501300); the CAMS Innovation Fund for Medical Sciences (CIFMS) (2021-I2M-1-005); and National High Level Hospital Clinical Research Funding (2025-PUMCH-D-001, 2022-PUMCH-B-013, D-009). This study was also funded and supported by Juventas Cell Therapy Ltd.

Primary Sjögren's syndrome (pSS) patients with low disease activity remain at risk for disease progression, yet predictive factors are poorly understood. We aimed to identify risk factors for disease worsening in pSS patients with initially low disease activity. We conducted a registry-based cohort study using prospectively collected data from the Chinese Rheumatism Data Center (CRDC). Patients with pSS meeting either 2002 AECG or 2016 ACR/EULAR classification criteria and baseline ESSDAI < 5 were included. Disease worsening was defined as ESSDAI increase ≥ 3 points during follow-up. Cox proportional hazards regression with LASSO selection identified independent risk factors. Among 745 patients (median age 46 years, 97.4

To evaluate whether low-to-moderate dose glucocorticoids provide additional benefit in primary Sjögren’s syndrome patients treated with hydroxychloroquine and/or iguratimod. Using the Chinese Rheumatism Data Center database, we emulated a pragmatic trial including 395 patients with primary Sjögren’s syndrome treated between May 2016 and August 2025. All patients received hydroxychloroquine and/or iguratimod as background therapy. Patients were categorized by glucocorticoid use: HCQ/IGU plus glucocorticoid group (≤ 30 mg/day prednisone equivalent, n = 188) or HCQ/IGU group (n = 207). Primary outcome was ESSDAI score change at 1 month. Secondary outcomes included ESSPRI scores and laboratory parameters. Treatment effects were estimated using overlap weighting of propensity scores. Stratified analyses examined subgroups by baseline ESSDAI, IgG levels, and arthritis status. After propensity score weighting, baseline characteristics were well-balanced. At 1 month, glucocorticoids provided no additional benefit in ESSDAI change compared to hydroxychloroquine/iguratimod (Cohen’s d = − 0.12; 95

Biosimilars need to demonstrate similarity in terms of quality, pharmacokinetics (PK), efficacy, safety, and immunogenicity. Here, we report the outcome of a comprehensive evaluation of the immunogenicity of the biosimilar BAT1806 compared with the tocilizumab reference product (TCZ). We conducted a post hoc analysis of study BAT1806-001-CR, a comparative PK study in healthy male volunteers (n = 129), and BAT1806-002-CR, a phase III, 52-week trial in patients with rheumatoid arthritis (n = 621). Anti-drug antibodies (ADA), ADA titers, and neutralizing ADA were measured, and their impact on PK, safety, and efficacy parameters were assessed. In BAT1806-001-CR, treatment-induced ADA were observed in 37.8

OBJECTIVES:As fibroblast-like synoviocyte activation and bone formation are associated with PsA, PET using the tracers of 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-sodium fluoride (NaF) may sensitively detect the disease. In this prospective study, we aimed to evaluate the performance of 68Ga-FAPI PET/CT in PsA and to compare it with 18F-NaF PET/CT. METHODS:Sixteen participants (female 7/16, age 42.31 ± 10.66 years) with PsA were prospectively enrolled and underwent dual-tracer PET/CT, clinical assessment and ultrasonography. PET/CT images were scored for PET-positive lesions at the peripheral joints, entheses, and axial joints. RESULTS:The positivity rate of 68Ga-FAPI in peripheral joints was higher than that in entheses and axial joints (21.84% vs 12.15% vs 0%), whereas high positivity rates of 18F-NaF in peripheral joints, entheses, and axial joints were observed (85.23%, 78.13% and 75%, respectively). The DAS 28 was higher in the PET-positive than in the PET-negative group with 68Ga-FAPI (5.25 ± 1.84 vs 2.55 ± 0.94, P = 0.037), but not with 18F-NaF. In addition, the PET joint count at 68Ga-FAPI PET/CT was positively correlated with the tender joint count (r = 0.604, P = 0.017), swollen joint count (r = 0.773, P = 0.001), DAS28-CRP (r = 0.556, P = 0.032), Psoriatic Arthritis Disease Activity Score (PASDAS) (r = 0.540, P = 0.038) and PsASon13 (r = 0.701, P = 0.005), while no correlation was observed in 18F-NaF PET/CT. CONCLUSION:The positivity rates of 68Ga-FAPI- and 18F-NaF PET/CT were different in patients with PsA in peripheral joints, entheses, and axial joints. The extent of joint involvement as shown in 68Ga-FAPI PET/CT correlated with clinical and US variables as well as with disease activity. TRIAL REGISTRATION:ClinicalTrials.gov, http://clinicaltrials.gov, NCT05686876.

Psoriatic arthritis (PsA), an inflammatory articular disease closely associated with psoriasis, is characterized by a wide range of symptoms including skin lesion, peripheral and axial joint involvement, enthesitis, and dactylitis. In recent years, significant advancements have been made in the treatment of PsA, promoting continuous improvement in patient outcomes. This article aims to comprehensively review the current status of drug treatment for PsA, encompassing not only new clinical evidence for conventional synthetic disease-modifying antirheumatic drugs(csDMARDs) but also an in-depth exploration of biologics or targeted synthetic disease-modifying antirheumatic drugs(tsDMARDs) against various targets in recent years. The objective of this study is to enhance clinicians' understanding of treatment strategies for PsA and provide more precise and effective treatment options for patients.

Patients with systemic lupus erythematosus (SLE) are at high risk of cardiovascular disease (CVD), fragility fractures, and malignancies. However, data regarding these comorbidities among Chinese SLE patients are limited. We aimed to determine the prevalence of and risk factors for these three major comorbidities in a large cohort of Chinese SLE patients. In this cross-sectional study, demographic, clinical, and common comorbidity profiles were obtained from the medical records of SLE patients enrolled in the Chinese SLE Treatment and Research group (CSTAR) registry. Univariate and multivariate logistic regression analyses were performed to identify possible risk factors related to these comorbidities. A total of 38,105 SLE patients were included (92.2

Current evidence demonstrates that rigorous adherence to the standardized diagnostic and therapeutic protocols outlined in the European League Against Rheumatism (EULAR) guidelines can markedly enhance renal survival rates in patients with lupus nephritis (LN) and lead to improved overall outcomes. Data on the real-world implementation of LN management guideline in China was limited. This study aimed to examine the implementation of the 2023 EULAR recommendations for systemic lupus erymatosus (SLE) and LN in China. Based on the Chinese Systemic Lupus Erythematosus Treatment and Research Group (CSTAR) cohort, patients with newly diagnosed active LN (24-h Urine Protein ≥ 0.5 g/L) from April 2009 to March 2022 were included. The initial immunosuppressant therapy, the adjustment of immunosuppressant, and the implementation of renal biopsy at baseline were assessed. The patients’ general conditions, clinical manifestations, the condition of rheumatologists and hospitals were included in the analysis. Of the 1518 enrolled patients, 787 (52

Conventional ultrasound (US) evaluation of enthesitis in psoriatic arthritis (PsA) is limited by its inability to quantify metabolic alterations such as hypoxia, a key driver of disease activity. We introduce an oxygenation-integrated multimodal photoacoustic/ultrasound (PA/US) imaging framework designed to quantify entheseal oxygen saturation (SO2) for assessing entheseal disease activity in PsA. In this cross-sectional study, 25 PsA patients underwent bilateral PA/US imaging of 12 entheses, where ultrasound lesions were scored using the Outcome Measures in Rheumatology scoring system, and PA-derived SO2 levels, quantified via dual-wavelength PA imaging, were classified into hyperoxia or hypoxia groups using k-means clustering. This approach provides metabolic insights complementary to conventional ultrasonic assessment. A composite score integrating hypoxia with US parameters was validated against clinical disease activity indices (Disease Activity Score 28-C-reactive protein, DAS28-CRP; Disease Activity Index for Psoriatic Arthritis, DAPSA). Among 300 entheses, 103 (34.3%) exhibited PA positivity, with 40 (38.8%) classified as hypoxia. Hypoxia scores independently predicted DAS28-CRP ([Formula: see text] = 0.618, p = 0.001) and DAPSA ([Formula: see text] = 0.612, [Formula: see text]). The hypoxia-optimized PAUS score demonstrated superior correlation with disease activity indices compared to conventional US (DAS28-CRP: r = 0.615, p = 0.001 versus r = 0.474, p = 0.017; DAPSA: r = 0.743, [Formula: see text] versus r = 0.567, p = 0.003), alongside superior diagnostic accuracy for minimal disease activity (area under the curve, AUC 0.776 versus 0.614, p = 0.008) and low disease activity (AUC 0.853 versus 0.772, p = 0.009). This multimodal scoring system enhances the stratification of PsA disease activity by providing unique metabolic insights, offering a potential tool for therapeutic monitoring and guiding treat-to-target strategies.

Background and Objectives:No prior studies have directly compared sirolimus with the standard of care (SoC) for lupus nephritis (LN) patients. This study aimed to compare the efficacy and safety of sirolimus with mycophenolate mofetil (MMF) for the treatment of LN. Methods:A real-world cohort study based on the Chinese SLE Treatment and Research (CSTAR) registry was conducted. Patients with active LN who were prescribed either sirolimus or MMF were enrolled. Propensity score matching was applied to ensure comparable baseline disease conditions. SLE disease activity indices, serological parameters, steroid doses, renal efficacy, and adverse events were evaluated at 3-month, 6-month, and 12-month follow-ups. Results:Data from 53 patients in each group were analyzed. Sirolimus demonstrated clinical effectiveness comparable to MMF, as evidenced by similar rates of lupus nephritis remission and lupus low disease activity state (LLDAS) /remission or a clinical response (reduction of SLE Disease Activity Index 2000 [SLEDAI-2K] ≥4 and increase in physician's global assessment [PhGA] < 0.3), as well as changes in 24-hour urine protein level, SLEDAI-2K score, PhGA score, and steroid tapering effect (P ≥ 0.05 at all follow-up timepoints). Notably, sirolimus group exhibited greater improvements in complement levels compared to MMF group at 3, 6, and 12 months. Ten adverse events in sirolimus group and one in MMF group were reported, with no severe adverse events. Conclusion:Sirolimus demonstrated comparable efficacy to MMF in the treatment of LN and glucocorticoid tapering, with additional benefits in serological improvement. Furthermore, sirolimus was well tolerated in LN patients, supporting its potential as a therapeutic option for LN.

ABSTRACT Lupus nephritis (LN) is one of the most severe manifestation of systemic lupus erythematosus (SLE). However, reliable tools for predicting LN risk remain limited. In this multicenter prospective cohort study, we developed, validated, and refined a risk stratification model for new‐onset LN. A total of 2441 SLE patients without baseline renal involvement were consecutively enrolled from the Chinese SLE Treatment and Research (CSTAR) registry, with 215 (8.8%) developed LN in a median follow‐up time of 3.5 years. A combination of clinical predictors, age < 30 years, absence of arthritis, serositis, hypocomplementemia, and positive anti‐double‐stranded DNA antibodies identified a clinical high‐risk group (n = 537, 22.0%) with a 3‐year LN incidence of 18.1%. The model was externally validated in 451 patients, with 50 developed LN in a median follow‐up time of 3.4 years. In these patients, a genetic risk score (GRS) derived from 112 SLE‐associated loci was found to be independently associated with LN (HR = 3.19, 95% CI, 1.83–5.55, p = 4.36 × 10−5). Among clinically low‐risk individuals, those in the highest GRS quartiles (81/451, 18.0%) showed elevated 3‐year LN incidence (15.5% vs. 1.4%). New‐onset LN may be predicted using a combination of clinical risk factors, and integrating GRS further improves risk stratification, enabling early identification of high‐risk patients.

This study evaluated the real-world effectiveness and safety of tacrolimus as a steroid-sparing maintenance therapy alone without additional biologics or immunosuppressive medications in systemic lupus erythematosus (SLE), particularly in mild, non–new-onset cases, with a focus on glucocorticoid-sparing effects and multi-organ remission. A retrospective analysis was conducted using data from 679 SLE patients in the Chinese SLE Treatment and Research Group (CSTAR) cohort. Patients received tacrolimus for ≥ 4 weeks alongside glucocorticoids and/or hydroxychloroquine were included. Patients on other immunosuppressants or biologics at baseline were excluded. The primary endpoint was the changes in SLE Disease Activity Index 2000 (SLEDAI-2 K). Secondary endpoints included SLE Responder Index-4 (SRI-4) response at weeks 4, 24, and 48 (≥ 4-point SLEDAI-2 K reduction with no new major flare), Physician Global Assessment (PGA) scores, remission of organ-specific disease manifestations, reduction in daily glucocorticoid dose, and safety. At baseline, 84.39

Importance:A recent study reported that methotrexate may reduce joint pain in patients with inflammatory hand osteoarthritis (OA). However, it remains unknown whether methotrexate has similar effects on inflammatory knee OA. Objective:To examine whether methotrexate has symptom-relieving and disease-modifying effects for participants with knee OA and effusion-synovitis. Design, Setting, and Participants:This multicenter, placebo-controlled randomized clinical trial was conducted at 11 sites in China between July 18, 2019, and January 15, 2023. Community-dwelling patients with inflammatory knee OA with effusion-synovitis on magnetic resonance imaging were included. Interventions:Participants were randomly assigned (1:1) to receive methotrexate, up to 15 mg weekly, or placebo using block randomization, stratified by study site. Main Outcomes and Measures:The primary outcomes were knee visual analog scale (VAS) pain change and effusion-synovitis maximal area change, over 52 weeks in the intention-to-treat population. Results:Of 278 participants screened, 215 participants (mean [SD] age, 60.4 [7.4] years; 191 [89%] female) were randomized (108 to the methotrexate group; 107 to the placebo group), and 175 (81%) completed the trial. Changes in VAS pain and effusion-synovitis maximal area were not significantly different between the methotrexate and placebo group over 52 weeks (between-group difference, 0.3 mm [95% CI, -6.7 to 7.3 mm] for VAS pain; 0.1 cm2 [95% CI, -0.8 to 1.0 cm2] for effusion-synovitis maximal area). No significant between-group differences were found for any of the prespecified secondary outcomes. At least 1 adverse event occurred in approximately 32 participants (29.6%) in the methotrexate group and 26 participants (24.3%) in the placebo group. Conclusions and Relevance:The results of this randomized clinical trial show that, compared to placebo, low-dose methotrexate did not reduce pain or effusion-synovitis over 52 weeks in patients with knee OA and effusion-synovitis. Trial Registration:ClinicalTrials.gov Identifier: NCT03815448.

BACKGROUND:Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS:SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS:Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION:This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING:This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Background To identify potential serum biomarkers for differentiating between axial psoriatic arthritis (axPsA) and peripheral psoriatic arthritis (pPsA). Methods Serum samples were collected from patients with PsA to create a biomarker discovery cohort and a verification cohort. Patients with PsA were classified into axial or peripheral subtypes based on imaging criteria. Untargeted proteomics technology was used in the discovery phase to screen for biomarkers, and candidate biomarkers were evaluated using enzyme-linked immunosorbent assay (ELISA) in the verification phase. Results We identified 45 significantly differentially expressed proteins (DEPs) between axPsA ( n = 20) and pPsA ( n = 20) with liquid chromatography-mass spectrometry. Among these DEPs, serum pigment epithelium-derived factor (PEDF) was identified as a candidate biomarker using the Boruta algorithm and lasso regression. Results of ELISA further confirmed that the level of serum PEDF expression was significantly higher in axPsA ( n = 37) than in pPsA ( n = 51) at the verification cohort (37.9 ± 10.1 vs. 30.5 ± 8.9 μg/mL, p < 0.001). Receiver operating characteristics analysis showed that PEDF had an area under the curve (AUC) of 0.72. Serum PEDF was positively correlated with body mass index and C-reactive protein. Additionally, there was a tendency towards a positive correlation between PEDF and the Bath Ankylosing Spondylitis Disease Activity Index. Conclusions This study provided a comprehensive characterization of the proteome in axPsA and pPsA and identified a candidate biomarker, PEDF, that may contribute to early diagnosis for axPsA.

To elucidate the sex-specific differences in demographic features, clinical characteristics, and quality of life in Chinese patients with psoriatic arthritis (PsA). A total of 1,074 patients with PsA registered between December 2018 and June 2021 from the Chinese REgistry of Psoriatic ARthritis (CREPAR) cohort were selected. The baseline data on demographics, clinical characteristics, commonly used laboratory tests, comorbidities, and quality of life assessments were collected for this cross-sectional analysis. A total of 1,074 patients were included in this study, 585 (54.47