Int J Rheum Dis
· 2026 Jun · PMID 42295039
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AIM: To determine the incidence, risk factors for, and mortality from interstitial lung disease (ILD) in patients with Rheumatoid Arthritis (RA) in Western Australia (WA). METHODS: A retrospective statewide cohort study...AIM: To determine the incidence, risk factors for, and mortality from interstitial lung disease (ILD) in patients with Rheumatoid Arthritis (RA) in Western Australia (WA). METHODS: A retrospective statewide cohort study of ILD in patients with RA (n = 5971) and age/sex matched controls (n = 20 830) hospitalized between 1985 and 2014. ILD was identified based on validated algorithms. ILD incidence (IR) per 1000 person-years (PY), odds ratio (OR) for risk factors and respiratory complications, and mortality rate (MR) per 1000 PY were estimated with 95% confidence intervals (CI). RESULTS: The IR of ILD in patients with RA (RAILD+) was increased (IR ratio 8.02, CI 6.28-10.32) and stable over 30 years. Age (OR 1.02, CI 1.01-1.03), smoking (OR 1.97, CI 1.48-2.63), and scleritis (OR 3.84, CI 1.86-7.94) were independent risk factors for ILD. Pulmonary infections, oxygen dependence, and lung cancer occurred as frequently in RAILD+ and CoILD+ but at higher rates than in participants without ILD in each group. MR for RAILD+ patients was higher than for RA patients not developing ILD (99.9 vs. 50.8; p < 0.01), but lower than for CoILD+ (166.3 vs. 99.9, p < 0.01). CONCLUSION: The incidence of ILD among patients with RA was stably increased over time. ILD increased respiratory morbidity and mortality in both RA and controls. Smoking cessation and early detection could reduce the risk and severity of ILD.
Int J Rheum Dis
· 2026 Jun · PMID 42252936
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BACKGROUND: The purpose of this study is to evaluate the global burden of hip osteoarthritis (OA) and investigate its risk factors using Global Burden of Disease (GBD) 2021 data and Mendelian randomization (MR). METHODS:...BACKGROUND: The purpose of this study is to evaluate the global burden of hip osteoarthritis (OA) and investigate its risk factors using Global Burden of Disease (GBD) 2021 data and Mendelian randomization (MR). METHODS: Hip OA burden was assessed by region, age, sex, and Socio-Demographic Index (SDI). Temporal trends were evaluated using Joinpoint regression-derived average annual percentage change (AAPC). Two-sample MR and mediation analysis explored causal risk factors. Future burden from 2022 to 2050 was primarily projected using a Bayesian age-period-cohort (BAPC) model, with autoregressive integrated moving average (ARIMA) analysis used as a sensitivity comparison. RESULTS: The global age-standardized hip OA prevalence was 416.01/100000 in 2021. The incidence and prevalence varied widely across countries. Males who were above 70 years old had a greater incidence of hip OA. The incidence and prevalence positively correlated with SDI, with the largest rise in incident cases occurring in middle SDI regions. Joinpoint analysis showed that the global burden of hip OA increased significantly from 1990 to 2021, with AAPCs of 0.2206 for incidence, 0.1879 for prevalence, and 0.1846 for DALYs. The most pronounced increases were observed in low-middle and middle SDI regions. High body mass index (BMI) contributed to a 21.2% increase in disability-adjusted life years (DALYs) from 1990 to 2021. MR mediation supported a positive association between higher BMI and hip OA and suggested that palmitoyl sphingomyelin may represent a potential mediator. The primary BAPC model suggested that the burden of hip OA would remain substantial through 2050, whereas comparison with ARIMA indicated model-dependent uncertainty in the long-term magnitude of the forecasts. CONCLUSIONS: Our study provides valuable insights into the global epidemiological trends and risk factors of hip OA. These findings can help formulate policies and allocate resources, although long-term projections should be interpreted cautiously because they are sensitive to model choice.
Shi X, Zhang J, Gao F
… +9 more, Kuang W, Deng J, Tan X, Li C, Li S, Gao J, Liu X, Sun B, Li C
Int J Rheum Dis
· 2026 Jun · PMID 42252933
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OBJECTIVES: Enthesitis-related arthritis (ERA) is a form of chronic inflammatory arthritis. Even when administered with a combination of non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic dr...OBJECTIVES: Enthesitis-related arthritis (ERA) is a form of chronic inflammatory arthritis. Even when administered with a combination of non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), and biologics, some patients remain in an active disease state. Antecedent studies have revealed that interleukin-17 (IL-17) plays an important role in the pathogenesis of ERA and have demonstrated the efficacy of IL-17 inhibitors. This real-world, retrospective study aimed to assess the efficacy and safety of secukinumab in patients with ERA. METHODS: This was a retrospective, single-center cohort study of 31 Chinese patients who had been diagnosed with ERA and treated with secukinumab for at least 3 months. The primary outcomes were the proportion of patients achieving JIA ACR 30/50/70/90/100 response criteria and ACR inactive disease, as well as the change in Juvenile Spondyloarthritis Disease Activity (JSpADA) Index from baseline. Secondary outcomes included changes in the number of joints with active arthritis and enthesitis, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). Outcomes were assessed every 3 months after secukinumab initiation. The Wilcoxon signed-rank test and paired t-test were used to analyze the data. RESULTS: Male predominance (24/31, 77.4%), late disease onset, HLA-B27 positivity (13/31, 41.9%), and enthesitis (10/31, 32.3%) were the key characteristics of our cohort. The median follow-up duration was 0.9 years (ranging from 0.4 to 2.7 years). At the last follow-up, ACR 30/50/70/90/100 response rates were 87% (27/31), 68% (21/31), 65% (20/31), 32.3% (10/31) and 12.9% (4/31); 25.8% (8/31) of patients achieved ACR inactive disease. JSpADA scores decreased from baseline (median 5.0, IQR: 3.5-5.0) to month 3 (median 3.5, IQR: 2.5-4.0; median difference = 1.25, Z = -4.26, p < 0.001, 95% CI: 0.8 to 2.0), to month 6 to 3.0 (IQR: 2.0-4.0; median difference = 1.5, Z = -3.85, p < 0.001, 95% CI: 1.0 to 2.3), month 9 to 3.0 (IQR: 1.0-3.0; median difference = 2.3, Z = -3.09, p = 0.002, 95% CI: 1.5 to -3.0) and month 12 to 2.5 (IQR: 1.0-3.0; median difference = 2.25, Z = -2.95, p = 0.003, 95% CI: 1.5 to 3.3). The mean active joint count decreased from 9.3 ± 0.7 at baseline to 3.3 ± 0.5 at 12 months. Normalization of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was observed. CONCLUSION: In this retrospective, single-center study, secukinumab appears to be associated with improvement in arthritis and disease activity in Chinese children with ERA. Further studies are needed to investigate the correlation between IL-17 and ERA.
Avcu A, Kaymaz-Tahra S, Kardas RC
… +19 more, Basibuyuk F, Uludağ Ö, Kerim D, San S, Kocaayan H, Ademoglu Z, Kenar Artin G, Ince B, Emmungil H, Akar S, Cefle A, Yazici A, Keser G, Aksu K, İnanc M, Onen F, Kucuk H, Direskeneli H, Alibaz-Oner F
Int J Rheum Dis
· 2026 Jun · PMID 42252894
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OBJECTIVES: Takayasu arteritis (TAK) may lead to arterial stenosis/occlusion and aneurysms, occasionally requiring vascular interventions. We evaluated outcomes, restenosis, and complications after vascular interventions...OBJECTIVES: Takayasu arteritis (TAK) may lead to arterial stenosis/occlusion and aneurysms, occasionally requiring vascular interventions. We evaluated outcomes, restenosis, and complications after vascular interventions in TAK and explored factors associated with restenosis. METHODS: We retrospectively included TAK patients who underwent extracardiac endovascular or surgical vascular interventions before or after TAK diagnosis across eight tertiary centers (1995-2024). Indications, disease activity status at the time of intervention, procedural characteristics, early/late outcomes, major complications, and restenosis were recorded. Restenosis was defined as > 70% stenosis on follow-up imaging performed ≥ 3 months after the procedure. Restenosis analyses were restricted to steno-occlusive lesions. RESULTS: We included 119 patients with 201 treated lesions (185 steno-occlusive lesions; 16 aneurysms/dissections). Of all procedures, 61.2% (n = 123) were performed after TAK diagnosis under immunosuppressive therapy. Follow-up imaging was available for 170/185 steno-occlusive procedures, and restenosis status was evaluable in 168 procedures; restenosis occurred in 82/168 (48.8%) with a median time to restenosis of 19.5 months. In exploratory Kaplan-Meier analysis, 1-, 3-, and 5-year restenosis-free patency rates were 76.8%, 63.6%, and 56.5%, respectively. In analyses restricted to post-diagnosis steno-occlusive procedures, crude restenosis was significantly less frequent under biologic therapy than without biologic therapy (30.8% vs. 53.1%; Fisher's exact p = 0.040); however, biologic therapy was not associated with time to restenosis in Cox regression (HR 1.01, 95% CI 0.51-1.99; p = 0.97) or patient-clustered Cox analysis (HR 1.01, 95% CI 0.47-2.18; p = 0.98). Major complication rates were 3.9% for endovascular procedures and 12.5% for surgical procedures. Overall mortality was 11.8%, with two deaths attributed to procedure-related complications. CONCLUSIONS: Vascular interventions in selected patients with Takayasu arteritis were associated with acceptable major complication rates. Among post-diagnosis steno-occlusive procedures, biologic therapy was associated with lower restenosis rates in crude analyses; however, this association was not sustained after accounting for restenosis timing. Therefore, the potential role of biologic therapy in improving post-interventional vascular outcomes should be interpreted cautiously and requires confirmation in prospective studies with standardized imaging surveillance.
Sato M, Saito T, Komiya Y
… +12 more, Noda S, Tagawa Y, Yamamoto A, Iwai H, Endo K, Koga H, Takahara Y, Sugimoto K, Sekiya I, Kawakami E, Hosoya T, Yasuda S
Int J Rheum Dis
· 2026 Jun · PMID 42246142
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OBJECTIVE: We investigated the role of GLI3, a transcription factor highly expressed in the pathogenic THY1CD34 sublining subset of rheumatoid arthritis synovial fibroblasts (RASFs), in regulating their pathogenic behavi...OBJECTIVE: We investigated the role of GLI3, a transcription factor highly expressed in the pathogenic THY1CD34 sublining subset of rheumatoid arthritis synovial fibroblasts (RASFs), in regulating their pathogenic behavior. METHODS: GLI3 protein levels were quantified in freshly isolated RASF subsets by Western blotting. Bulk RASFs were subjected to siRNA-mediated knockdown (KD) of GLI3 or GLI1, followed by RNA sequencing. The effects of GANT61 on RASF proliferation, cell-cycle progression, migration, viability, and apoptosis were assessed using EdU/PI analysis, scratch assays, CCK-8 assays, and Annexin V/PI flow cytometry. RESULTS: GLI3 expression was enriched in THY1CD34 RASFs at both mRNA and protein levels. GLI3 KD increased GLI1 expression and upregulated genes involved in inflammation, matrix remodeling, and cell cycle regulation, including IL6, IL11, IL24, IL33, MMP3, PLAU, CCNA2, and E2F1. Pathway enrichment analysis revealed activation of ECM-receptor interaction, PI3K-Akt, and TNF signaling. Co-silencing GLI1 with GLI3 blunted the induction of IL11, IL24, IL33, CCNA2, E2F1, and PLAU observed with GLI3 KD alone, indicating that GLI1 mediates a subset of the transcriptional effects induced by GLI3 loss. GANT61 suppressed CCNA2 and E2F1 expression, inhibited RASF proliferation and migration, and did not markedly increase apoptosis. CONCLUSION: GLI3 functions as a negative regulator of GLI1 and its downstream targets that drive the pathogenic behavior of RASFs. Targeting the GLI1-GLI3 axis may represent a promising therapeutic strategy to modulate fibroblast-driven inflammation and joint destruction in RA.
Int J Rheum Dis
· 2026 Jun · PMID 42241050
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OBJECTIVES: Low bone mineral density (LBMD), a major osteoporotic fracture risk factor, disproportionately affects females globally. This study analyzing its burden through trends, health inequities, and predictive model...OBJECTIVES: Low bone mineral density (LBMD), a major osteoporotic fracture risk factor, disproportionately affects females globally. This study analyzing its burden through trends, health inequities, and predictive modeling. METHODS: Data from the Global Burden of Disease (GBD) 2021 were used to extract summary exposure values (SEV), mortality, and disability-adjusted life years (DALYs) for LBMD. Temporal trends, demographic and epidemiological changes, health inequalities, and projections were analyzed. RESULTS: In 2021, the global age-standardized rate of SEV was 23.51 (0-100 scale), declining at an AAPC of -0.16 since 1990. The age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) were 5.65 (95% UI: 4.71, 6.40) and 204.99 (95% UI: 168.92, 242.95) per 100 000 population, respectively, and both declined from 1990 to 2021. SEV was higher in females than males (28.56 vs. 18.08), while ASMR (4.99 vs. 6.45) and ASDR (196.37 vs. 211.01) were higher in males. Inequality slope indices in DALYs showed widening gaps between highest and lowest SDI countries, from -26.31 in 1990 to -53.34 in 2021. The absolute burden was mainly driven by population growth and aging, and ASMR and ASDR are expected to continue declining through 2050. CONCLUSION: Although the age-standardized burden of LBMD declined from 1990 to 2021, the absolute burden remained substantial and was largely driven by population growth and aging. The burden was concentrated in low-SDI regions, while some high-SDI regions showed unfavorable trends. Females had higher exposure levels, whereas males bore a greater overall disease burden. Reducing the global LBMD burden requires improved nutrition and care in low-SDI regions, targeted prevention in postmenopausal women, and earlier detection and treatment in men.