Int J Rheum Dis
· 2026 May · PMID 42106869
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BACKGROUND: Updated, country-specific burden curves for rheumatoid arthritis (RA) across the Asia-Pacific region remain limited. We aimed to quantify long-term trends in RA prevalence, incidence, mortality, and disabilit...BACKGROUND: Updated, country-specific burden curves for rheumatoid arthritis (RA) across the Asia-Pacific region remain limited. We aimed to quantify long-term trends in RA prevalence, incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2023, and to project short-term burden to 2025. METHODS: We extracted age-standardized rates (ASRs) and absolute counts for rheumatoid arthritis from the Global Burden of Disease (GBD) 2023 study for 27 Asia-Pacific countries and territories. Temporal trends were summarized using average annual percent change (AAPC) estimated from joinpoint regression, and short-term projections to 2025 were generated using Bayesian age-period-cohort models. Decomposition analysis quantified the relative contributions of population aging, population growth, and changes in age-specific rates to observed increases in prevalent cases. RESULTS: Between 1990 and 2023, the regional age-standardized prevalence rate of rheumatoid arthritis increased by approximately 16%, reaching 126 per 100 000 population in 2023, and is projected to rise further to 131 per 100 000 (95% uncertainty interval [UI] 124-138) by 2025. Age-standardized incidence increased from 10.0 to 11.6 per 100 000, with a projected rate of 12.1 per 100 000 (95% UI 11.2-13.0) in 2025. In contrast, age-standardized mortality declined by 43% (from 0.75 to 0.43 per 100 000), and DALY rates decreased modestly (from 45.3 to 41.8 per 100 000), although absolute DALYs increased due to demographic expansion. Decomposition analysis indicated that 84% of the net increase in prevalent RA cases was attributable to population aging and growth, with only 16% associated with rising age-specific prevalence rates. Female-to-male prevalence ratios remained stable at approximately 2.3-2.4 throughout the study period. The fastest relative increases were observed in lower-middle-income South-East Asian countries, while several high-income Western-Pacific countries showed stable or declining rates. CONCLUSIONS: The expanding burden of rheumatoid arthritis in the Asia-Pacific region is driven predominantly by demographic momentum rather than worsening per-capita risk. Although mortality and per-capita disability are declining, absolute health loss will continue to rise under population aging. Integrating early RA care with population-level prevention targeting modifiable risk factors may mitigate future burden growth.
Tada M, Matsumoto Y, Nakamura T
… +2 more, Goto H, Matsuura M
Int J Rheum Dis
· 2026 May · PMID 42101027
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INTRODUCTION: Cognitive impairment is increasingly recognized as a clinically relevant comorbidity in patients with rheumatoid arthritis (RA). Although chronic inflammation has been implicated in cognitive vulnerability,...INTRODUCTION: Cognitive impairment is increasingly recognized as a clinically relevant comorbidity in patients with rheumatoid arthritis (RA). Although chronic inflammation has been implicated in cognitive vulnerability, the relationship between RA-related inflammatory markers and cognitive function has not been fully elucidated. METHODS: In this cross-sectional study, patients with RA underwent cognitive assessment using the Mini-Mental State Examination (MMSE). Serum matrix metalloproteinase-3 (MMP-3) and erythrocyte sedimentation rate (ESR) were evaluated as inflammatory markers. Multivariable linear regression analyses were performed to examine factors associated with MMSE score, adjusting for age, sex, educational level, and frailty. Sensitivity analyses included additional adjustments for ESR, renal function, and glucocorticoid use. Mild cognitive impairment (MCI), defined as an MMSE score ≤ 27, was examined using logistic regression models. RESULTS: A total of 130 patients were included, of whom 34 were classified as having MCI. Higher serum MMP-3 levels were associated with lower MMSE scores after adjustment for demographic factors, educational level, and frailty. This association remained significant after additional adjustment for ESR, whereas ESR itself was not associated with MMSE score in fully adjusted models. Higher MMP-3 levels were also associated with increased odds of MCI, and this association remained significant in analyses restricted to female patients. CONCLUSIONS: Serum MMP-3 levels were associated with cognitive function in patients with RA, whereas ESR was not. These findings suggest that RA-related inflammatory activity reflected by MMP-3 may be relevant to cognitive vulnerability beyond nonspecific inflammation. Further longitudinal studies are warranted to clarify temporal relationships and clinical implications of these findings.
Int J Rheum Dis
· 2026 May · PMID 42095393
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Women bear a disproportionate burden of knee osteoarthritis (KOA), yet global research systematically underrepresents sex-specific and context-sensitive analyses, limiting precision care and equitable interventions. We c...Women bear a disproportionate burden of knee osteoarthritis (KOA), yet global research systematically underrepresents sex-specific and context-sensitive analyses, limiting precision care and equitable interventions. We conducted a scoping review following PRISMA-ScR guidelines, systematically mapping studies on KOA in adults from 2000 to 2024 across PubMed, Embase, Scopus, Web of Science, and Cochrane Library. A predefined, version-controlled protocol was maintained with timestamped revisions and an independent audit to ensure methodological transparency. Dual independent screening, data extraction, and coding achieved high reliability (Cohen's κ = 0.87). A validated weighted gap scoring system assessed four equity domains: sex-disaggregated analysis, women's representation, contextual reporting, and geographic diversity. Integrated descriptive mapping and cross-tabulation quantified structural evidence gaps. Gray literature and non-English studies were excluded, acknowledging potential underrepresentation of low- and middle-income country (LMIC) data. Among 287 included studies, women were represented in 91%, yet only 22% were women-only cohorts, with high-income countries 2.4× more likely to conduct women-focused research than LMICs (χ = 29.4, p < 0.001). Sex-disaggregated analyses were reported in 38% of mixed-sex studies, with profound neglect of psychosocial, preventive, and mechanistic outcomes. Intersectional analyses combining age, socioeconomic status, and context were extremely rare. Weighted gap scores highlighted very high deficiencies in SES, education, occupation, and LMIC representation, with minimal improvement over 24 years. KOA's evidence base does not merely underrepresent women; it systematically fails to generate clinically validated knowledge for them. As a result, interventions are routinely applied without clear evidence of the effectiveness across the population most affected, without mandatory sex-aggregated, mechanistic, and context-specific research.
Kashyap S, Pandey AK, Kumar P
… +3 more, Kanjilal M, Kumar U, Thelma BK
Int J Rheum Dis
· 2026 May · PMID 42087570
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OBJECTIVES: ARL15, coding for a small GTPase, was identified as a non-HLA susceptibility gene in rheumatoid arthritis (RA) through a GWAS in a North Indian cohort, with serum adiponectin and ARL15 levels higher in RA pat...OBJECTIVES: ARL15, coding for a small GTPase, was identified as a non-HLA susceptibility gene in rheumatoid arthritis (RA) through a GWAS in a North Indian cohort, with serum adiponectin and ARL15 levels higher in RA patients with the associated genotype. This study aimed to delineate the functional role of ARL15 in RA pathobiology. METHODS: Differential transcriptomics in both ex vivo RA synovial fibroblasts and in vitro MH7A cells using a gene knockdown (KD) approach and standard analyses pipeline were performed to obtain insights into ARL15's role. RESULTS: In RASF, ARL15 KD led to downregulation of COMP-an extracellular matrix stabilizer linked to severe RA-alongside upregulation of adiponectin and IFN response genes like IFI6 and USP18. Furthermore, upregulation of NPTX1 and MX1, previously associated with disease modulation and treatment response, was observed. Downregulation of CTGF, CD248, and PTX3 suggested involvement of ARL15 in inflammation and RA-associated cardiovascular risk. Conversely, ARL15 KD in MH7A cells displayed distinct signatures with upregulated cytokines (IL1A, IL8, CXCLs) and downregulated inflammatory regulators (DOCK2, TLR4, TGFB2), reflecting an inflammatory bias distinct from patient-derived RASF. CONCLUSION: The dual-system approach, despite its divergent differential expression, underscores the multifaceted role of ARL15 in regulating connective tissue architecture, inflammation, and immune response. Limitations of immortalized cell models in capturing patient heterogeneity and disease complexity are apparent, but the key findings position ARL15 as a promising therapeutic target, warranting further investigation in RA animal models and genomic medicine. Taken together, this work provides a compelling rationale to pursue ARL15 targeted interventions in RA management.
Int J Rheum Dis
· 2026 May · PMID 42084335
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BACKGROUND: Although artificial intelligence (AI) is increasingly recognized for enhancing efficiency in healthcare services, its role in exercise and rehabilitation strategies remains unclear. OBJECTIVES: To assess the...BACKGROUND: Although artificial intelligence (AI) is increasingly recognized for enhancing efficiency in healthcare services, its role in exercise and rehabilitation strategies remains unclear. OBJECTIVES: To assess the quality, reliability, accuracy, and readability of three large language models (LLMs), ChatGPT-5, DeepSeek-R1, and Gemini 2.5, in response to questions commonly asked by patients with rheumatoid arthritis (RA) regarding exercise and rehabilitation strategies. METHODS: Using a cross-sectional comparative design, a structured assessment framework was developed that included exercise- and rehabilitation-related questions grouped into five thematic domains between 22 and 29 September 2025: exercise and physical activity (S1), hand function (S2), joint protection techniques (S3), breathing and pulmonary health (S4), and general topics (S5). Information quality was evaluated with the modified DISCERN tool, while content reliability was evaluated with the Reliability Score, and accuracy was measured using a five-point likert Accuracy Scale. Readability was determined through the Flesch Reading Ease scale. RESULTS: DeepSeek-R1 and ChatGPT-5 achieved significantly higher scores for quality, reliability, accuracy, and readability compared with Gemini 2.5. In the S1 and S2 subgroups, both models consistently outperformed Gemini 2.5 across all evaluation metrics. Mean readability scores were 50.20 for DeepSeek-R1, 46.66 for ChatGPT-5, and 37.33 for Gemini 2.5, indicating that all responses were classified as difficult to read. CONCLUSIONS: This study highlighted that DeepSeek-R1 and ChatGPT-5 generated more accurate and reliable RA-related responses than Gemini 2.5; however, the complex language used by all models may limit accessibility for patients with low health literacy, underscoring the need for professional supervision in RA exercise planning.
Aghasili CC, Odai RL, Mensah SA
… +8 more, Mate-Kole M, Eyiah N, Kopah T, Orhin A, Opoku IA, Ogieuhi IJ, Atafo GI, Matsumura ME
Int J Rheum Dis
· 2026 May · PMID 42084304
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AIM: To examine national trends and disparities in cardiovascular mortality associated with systemic connective tissue disorders (CTDs) in the United States from 1999 to 2020. METHODS: We analyzed mortality data from the...AIM: To examine national trends and disparities in cardiovascular mortality associated with systemic connective tissue disorders (CTDs) in the United States from 1999 to 2020. METHODS: We analyzed mortality data from the CDC WONDER database. Deaths were included where CTD (ICD-10: M05, M06, M30-M35) was the underlying cause and cardiovascular disease was a contributing cause. Age-adjusted mortality rates (AAMRs) per 1 000 000 were calculated using the 2000 US Standard Population. Joinpoint regression identified annual and average annual percentage changes. Analyses were stratified by sex, race/ethnicity, census region, and urbanization. Disease subgroup and state-level analyses were performed. RESULTS: Between 1999 and 2020, 47 752 cardiovascular deaths occurred among individuals with systemic CTDs. The national AAMR declined from 14.4 to 8.2 per 1 000 000 (AAPC: -2.68%, 95% CI: -2.89 to -2.47, p < 0.001). Females had consistently higher mortality than males (average AAMR: 13.5 vs. 5.9 per 1 000 000; p < 0.001). Non-Hispanic Black individuals had the highest rates (average AAMR: 14.9 per 1 000 000), with widening disparities after 2008. Rural areas had higher mortality than urban areas (average AAMR: 11.4 vs. 9.9 per 1 000 000; p = 0.01). Subgroup analyses revealed heterogeneous trends across CTD subtypes, with SLE showing the slowest improvement (AAPC: -1.87%) and dermatomyositis the steepest decline (AAPC: -4.98%). State-level AAMRs ranged 2.2-fold, from 6.3 (District of Columbia) to 13.6 (Montana) per 1 000 000. CONCLUSIONS: Cardiovascular mortality associated with systemic CTDs has declined significantly over two decades; however, persistent racial disparities, urban-rural differences, heterogeneous disease-specific trends, and substantial geographic variation underscore the need for targeted, equitable interventions in this high-risk population.