Arthritis Research & Therapy最新文献

Objective: Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease. Early referral to a specialized center is crucial for prompt diagnosis and treatment. This study aims to develop and validate a scoring system to assist clinicians in efficiently identifying and referring patients suspected of having non-systemic JIA.

Methods: We conducted a cohort study with a mixed design (retrospective and prospective), involving consecutive patients presenting with joint complaints who were referred for the first time to the Pediatric Rheumatology Unit at ASST G. Pini-CTO Hospital. The model was developed using multivariate logistic regression with bootstrap resampling and the Lasso (Least Absolute Shrinkage and Selection Operator) method for variable selection.

Results: A total of 342 patients were included, of whom 61 (18%) were diagnosed with JIA. The selected variables for the model were: type of joint (large), daily symptoms, joint swelling, activity as a precipitating factor, a positive squeeze test of the metatarsophalangeal/metacarpophalangeal (MTP/MCP) joints, normal bending of the interphalangeal (IF) joints of the hands, morning limping and/or stiffness, and sacroiliac tenderness. The ROC curve, based on the model's regression score, showed an AUC of 0.92 with an overall accuracy of 0.88 (95% CI: 0.84-0.91) using a cutoff of 3 points, yielding a sensitivity of 95% and a specificity of 71%. Initial internal validation of the model revealed an AUC of 0.92 (95% CI: 0.89-0.95).

Conclusion: This study presents and initially validates a simple and efficient scoring system to aid clinicians in the early referral of patients suspected of having non-systemic JIA.

Clinical trial number: Not applicable.

Background: Gender differences in clinical manifestations and disease progression of systemic lupus erythematosus (SLE) have been well documented; however, there is a paucity of literature on the gender differences in the quality of life (QOL) of patients with SLE, especially in the context of organ-specific damage. This study aimed to explore gender differences in the clinical features and patient-reported outcomes among Japanese patients with SLE, with particular focus on the effect of joint and cardiac damage on gender-based disparities in QOL: previous studies have shown that articular and cardiac damage are associated with impaired health-related HR QOL (HRQOL).

Methods: In this retrospective, cross-sectional multicenter cohort study, we used data from 1297 Japanese patients with SLE (159 males (12.3%) and 1138 females (87.7%)) enrolled in a nationwide multicenter registry (LUNA), and compared the clinical variables, organ damage scores (SLICC/ACR Damage Index [SDI]), and QOL (assessed using the LupusPRO questionnaire) between the sexes. Additionally, subgroup analyses were performed for patients with arthritis/joint damage, cardiac damage, and according to disease activity (lupus low disease activity state, LLDAS).

Results: The median age of our cohort was 51 years (interquartile range, 40-63 years). Male patients had a shorter disease duration and were older at disease onset than females. The disease activity scores were slightly lower in male patients, whereas SDI was slightly higher in females. Male patients exhibited lower rates of articular/joint damage (1.26% versus 4.66%, p = 0.046) but higher rates of cardiac damage (11.3% versus 7.15%, p = 0.015) than females. The LupusPRO indicated higher HRQOL scores for male patients with SLE than female patients (87.4 versus 80.5, p = 0.001); however, the difference of HRQOL became unclear between both sexes in the presence of arthritis/joint damage and cardiac damage.

Conclusion: Japanese male patients with SLE have a relatively higher HRQOL than females; however, this change became unclear in patients with SLE who had joint or cardiac damage. Further investigations are needed to clarify exact contributing factors for better HRQOL in male patients with SLE.

Background: Sarilumab (SAR), an interleukin-6 receptor inhibitor (IL-6Ri), and Janus kinase inhibitors (JAKi) are approved options for rheumatoid arthritis (RA) when methotrexate (MTX) cannot be used. Real-world evidence for MTX-free monotherapy remains limited.

Methods: We conducted a multicenter retrospective cohort study of RA patients receiving SAR or JAKi as MTX-free monotherapy. To reduce confounding, 1:1 propensity score matching was performed in the overall cohort (n = 252, 126 per group) and separately within treatment-line strata: Phase 2 first-line biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs: 45 per group), Phase 3 second-line b/tsDMARDs (53 per group), and Phase 3 ≥ third-line b/tsDMARDs (47 per group). Outcomes over 12 months included drug retention, change in Clinical Disease Activity Index (CDAI), glucocorticoid (GC) tapering and discontinuation, low disease activity (LDA, CDAI ≤ 10), and safety profiles. Predictors of LDA were evaluated with logistic regression. This multicenter real-world.

Results: Across matched strata by prior b/tsDMARDs, retention and CDAI change did not differ significantly between SAR and JAKi through 12 months. When classified by cause, adverse events (AEs)-related discontinuation was higher with JAKi, yielding lower AE-specific retention. Both groups demonstrated GC sparing overtime, with a greater increase in GC discontinuation for SAR than for JAKi in Phase 2. Baseline predictors of achieving LDA at 12 months included higher C-reactive protein (CRP) and platelet count (Plt) in both groups, with additional associations of younger age and lower hemoglobin (Hb) in the SAR. In safety analyses, overall AEs were less frequent with SAR than with JAKi, driven by lower risks of infection including herpes zoster, while other categories were similarly infrequent.

Conclusion: SAR and JAKi showed no statistically significant differences in 12-month retention or disease control in MTX-free monotherapy settings. Higher CRP and Plt with lower Hb, particularly in younger patients, identified better response to SAR and support biomarker guided selection between IL-6Ri and JAKi. In Phase 2, GC discontinuation with SAR suggests a practical strategy to reduce AEs while maintaining efficacy. Prospective studies should validate these findings and define actionable thresholds.

Background: Subcutaneous adalimumab is the preferred treatment for most children with juvenile idiopathic arthritis (JIA) and non-infectious uveitis, usually administered every other week. Some patients do not respond or lose responsiveness over time, leading to dose escalation to weekly administration. This study evaluated the efficacy and pharmacokinetics of weekly subcutaneous adalimumab in children with JIA and idiopathic uveitis.

Methods: This is a retrospective study on clinical and pharmacokinetic characteristics of patients treated with subcutaneous adalimumab for psoriatic arthritis or non-infectious uveitis (idiopathic or JIA-associated) who did not respond or ceased to respond to biweekly administration.

Results: Four patients were enrolled: three females and one male, with a median age of 15 years (range 7-18; IQR 6). One had juvenile psoriatic arthritis, two had idiopathic uveitis, and one had JIA-related uveitis. They all presented a poor control of the disease on biweekly administrations, while it was successfully controlled on weekly administrations. None of them presented adverse events. Pharmacokinetic analyses identified two groups of patients: those with high clearance and those with low clearance. In both groups, weekly dosing increased the predicted drug concentrations, and in patients with high clearance only weekly administration provided the predicted concentration exceeding the therapeutic cut-off of 9.6 mg/L.

Conclusions: Weekly adalimumab administrations were safe and effective in controlling both articular and ocular inflammation. In cases where the disease is poorly controlled with regular biweekly administrations, we encourage escalating adalimumab treatment to weekly administration before adding other therapies or switching to different biologics.

Background: Chronic pain and psychiatric comorbidities in juvenile idiopathic arthritis (JIA) persist even during disease remission, suggesting central nervous system (CNS) alterations. This study used proton magnetic resonance spectroscopy (¹H-MRS) to investigate neurometabolic changes in the right hippocampus of JIA patients across active and inactive disease phases.

Methods: A cohort of 248 JIA patients (61 treatment-naïve patients with active JIA and 187 patients with inactive JIA) and 57 healthy controls (HCs) underwent ¹H-MRS of the right hippocampus. Metabolite ratios of total N-acetylaspartate (tNAA), total choline (tCho), myo-inositol (mI), glutamate (Glu), and glutamate-glutamine complex (Glx) relative to total creatine (tCr) were quantified. Associations with systemic inflammation (ESR and CRP) and clinical indices (JADAS-27 and CHAQ) were evaluated.

Results: Compared with HCs, both JIA groups showed elevated mI/tCr and reduced Glu/tCr and Glx/tCr in the inactive JIA group (all, P < 0.05). mI/tCr was positively correlated with ESR (rho = 0.269) and CRP (rho = 0.287) in active JIA patients. However, the results did not survive the rigid multiple correction. Notably, tNAA/tCr, tCho/tCr, Glu/tCr and Glx/tCr showed no significant correlations with systemic inflammation and clinical indices for treatment-naïve and inactive JIA patients.

Conclusions: Sustained hippocampal neuroinflammation (indicated by elevated mI/tCr) and the subsequent glutamatergic synaptic dysfunction (indicated by reduced Glu/tCr and Glx/tCr) were identified in JIA patients. Peripheral inflammation may drive microglial activation during active disease, highlighting the hippocampus as a vulnerable CNS target in chronic inflammatory states.

Background: Temporomandibular joint osteoarthritis (TMJOA) is a prevalent inflammatory disease with unclear pathogenesis. Serum and glucocorticoid-inducible kinase 1 (SGK1) has been implicated in osteoarthritis-related cartilage degeneration. This study investigated the role of SGK1 in a mouse model of TMJOA and explored its mechanism, focusing on SGK1's regulation of Forkhead box O1 (FoxO1) and its subsequent effects on autophagy and extracellular matrix degradation in mouse condylar chondrocytes (MCCs).

Methods: A TMJOA model was established using unilateral anterior crossbite (UAC), and an SGK1 knockdown model was generated via intra-articular injection of AAV virus.

Results: SGK1 expression was significantly upregulated in condylar cartilage of UAC-induced TMJOA mice. SGK1 knockdown alleviated cartilage matrix degradation and increased the expression of anabolic marker. In MCCs, SGK1 directly bound to FoxO1, promoting its phosphorylation and nuclear export, thereby inhibiting autophagy. Inhibiting SGK1 enhanced autophagy, as evidenced by increased Beclin-1, elevated LC3-II/LC3-I ratio, and decreased P62, which consequently attenuated IL-1β-induced extracellular matrix catabolism. These effects were reversed by autophagy inhibitor chloroquine and FoxO1 inhibitor AS1842856.

Conclusions: This study is the first to propose the regulatory role of SGK1 in TMJOA, providing new insights for future therapeutic research.

Objective: To investigate serum CXCL6 as a biomarker at diagnosis and predict progression of interstitial lung disease (ILD) in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Baseline serum CXCL6 levels were measured in 292 AAV patients and 82 healthy controls. Correlations with clinical parameters and disease activity were examined. To assess its role in ILD progression, the association between baseline CXCL6 levels and ILD progression during follow up was evaluated using univariable and multivariable analyses.

Results: Serum CXCL6 levels were significantly elevated in AAV patients compared to healthy controls, and were markedly higher in those with ILD than without ILD. The frequency of ILD in AAV patients with high serum CXCL6 levels was significantly higher compared with low levels group (54% vs. 36%, P = 0.002). Serum CXCL6 levels at baseline correlated positively with disease activity of AAV, and acute-phase reactants (ESR and CRP). Among AAV-ILD patients, high serum CXCL6 levels were associated with a significantly higher frequency of ILD progression during follow-up compared to low levels (53.8% vs. 30.0%, P = 0.023). Critically, high baseline CXCL6 level was independently associated with ILD progression in multivariate regression analysis.

Conclusions: This exploratory study suggests that elevated serum CXCL6 levels are associated with greater frequency and disease progression of ILD in AAV patients. Serum CXCL6 may represent a promising serological biomarker for identifying AAV-ILD and monitoring its progression.

Background: The influence of physical activity (PA) patterns on gout risk is unclear. We investigated the associations of accelerometer-derived PA patterns, specifically regularly active (RA) and weekend warrior (WW), with incident gout.

Methods: We analyzed 97,387 gout-free UK Biobank participants with 7-day wrist-worn accelerometer data. Participants were categorized as inactive (< 150 min/week moderate-to-vigorous PA [MVPA]), WW (≥ 150 min MVPA with ≥ 50% concentrated in 1-2 days), or RA (≥ 150 min MVPA, not meeting WW criteria). Multivariable Cox models estimated hazard ratios (HRs) for incident gout.

Results: During a median 8.0 years' follow-up, 833 gout cases occurred. In minimally adjusted models, both RA (HR = 0.67, 95% CI: 0.55-0.83, P < 0.001) and WW (HR = 0.76, 95% CI: 0.65-0.89, P < 0.001) patterns showed reduced risk compared to inactive pattern. However, results diverged after further adjustment for baseline sUA: the RA pattern maintained a robust protective association (HR = 0.79, 95% CI: 0.65-0.98, P = 0.029), whereas the association for the WW pattern was attenuated and lost statistical significance (HR = 0.93, 95% CI: 0.79-1.08, P = 0.331). Subgroup analyses revealed significant interactions with comorbidities (P for interaction < 0.01), where the WW pattern showed no inverse association in participants with hypertension or chronic kidney disease, while RA remained protective. These findings were robust across sensitivity analyses and genetic risk strata.

Conclusion: While any moderate-to-vigorous physical activity is beneficial, the regularly active pattern demonstrates a more robust inverse association with gout than the weekend warrior pattern. Regularity in physical activity appears crucial for gout risk reduction, particularly for metabolically vulnerable individuals, as the sporadic nature of the weekend warrior pattern may be insufficient to counteract established metabolic risks.