Danilo Sosa,1 Leandro Llugain,1 Sofia Maissonave Strazzarino,2 Valentina Zubiaurre,3,4 Alvaro Danza1,5 1Department of Internal Medicine, Facultad de Medicina, Universidad de la República, Hospital Pasteur, Administración de los Servicios de Salud del Estado (ASSE), Montevideo, Uruguay; 2Unidad Académica de Métodos Cuantitativos, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; 3Maternal-Fetal Medicine Unit –(Department of Gynecology and Obstetrics), Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay; 4Fondo Nacional de Recursos, Montevideo, Uruguay; 5External Medical Reviewer, Fondo Nacional de Recursos (2019– 2025), Montevideo, UruguayCorrespondence: Alvaro Danza, Department of Internal Medicine, Facultad de Medicina, Universidad de la República, Hospital Pasteur, Administración de los Servicios de Salud del Estado (ASSE), Montevideo, Uruguay, Tel +59824800285, Email alvarodanza@gmail.comPurpose: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis comprises multisystemic diseases treated with glucocorticoids combined with cyclophosphamide or rituximab. In Uruguay, the National Resources Fund (Fondo Nacional de Recursos, FNR) covers rituximab for selected patients with ANCA-associated vasculitis. This study aimed to describe the characteristics and clinical course of patients treated with rituximab under this coverage mechanism.Patients and Methods: An observational, analytical, retrospective cohort study was performed. Adult patients with ANCA-associated vasculitis whose rituximab treatment was approved by the FNR were included. Demographic, clinical, serologic, therapeutic, and safety variables were recorded. Baseline assessment, at the first rituximab cycle (T0), was compared with assessment at the second cycle (T1).Results: Fifty-eight patients were included; 28 (48.3%) were women. Mean age was 58.6 (12.9) years. Granulomatosis with polyangiitis was the predominant clinical form (70.7%). Rituximab was used for refractory disease in 32 patients (55.2%) and for relapse in 26 (44.8%). Forty-three patients (74.1%) had a T1 assessment, with a median interval of 6.9 months between cycles. Median Birmingham Vasculitis Activity Score (BVAS) fell from 18.5 points at T0 to 7.0 points at T1 (p < 0.001); 25 patients (58.1%) had a reduction of at least 50% from baseline. Median urine protein-to-creatinine ratio decreased from 0.395 to 0.05 g/g (p = 0.012). Median serum creatinine decreased from 1.3 mg/dL to 1.1 mg/dL (p = 0.11). Median daily prednisone dose fell from 30 to 5 mg/day (p < 0.001). Eight deaths were recorded (13.8%); four occurred within the first six months after the first rituximab dose.Conclusion: In this national cohort of patients with refractory or relapsing ANCA-associated vasculitis, rituximab was associated with a significant reduction in disease activity and glucocorticoid dose. Proteinuria also decreased significantly; serum creatinine did not. These findings provide real-world data on rituximab use in Uruguay and are consistent with international evidence.Keywords: ANCA-associated vasculitis, rituximab, granulomatosis with polyangiitis, microscopic polyangiitis, glucocorticoids, real-world evidence
Yangfan Chen, Zongwen ShuaiDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of ChinaCorrespondence: Zongwen Shuai, Email amushuaizw@163.comObjective: To explore clinical and immunological factors associated with disease activity in myeloperoxidase‑antineutrophil cytoplasmic antibody‑associated vasculitis (MPO‑AAV), and analyze cross‑sectional correlations of renal impairment, anemia and antinuclear antibodies (ANA) with disease activity.Methods: In this retrospective study, 82 consecutive hospitalized MPO‑AAV patients (September 2023‑February 2025) were stratified into high‑ and low‑activity groups using BVAS‑3 (cut‑off > 15 points). Baseline clinical and laboratory data were compared. Spearman correlation and univariate‑multivariate logistic regression were applied to evaluate correlates of high disease activity.Results: Compared with low‑activity patients, the high‑activity group had higher serum creatinine (172.5 (86.2– 310.7) vs 72.1 (52.3– 103.5)), lower eGFR (46.70 ± 36.53 vs 86.92 ± 27.29) and hemoglobin (90.54 ± 20.53 vs 110.69 ± 18.43) (all P< 0.001), as well as a higher rate of kidney injury (69.57% vs 13.89%, P< 0.001). ANA positivity showed only marginal inter‑group difference (P=0.075). BVAS‑3 was strongly correlated with creatinine (r= 0.621(0.461~0.743)), eGFR (r= − 0.712(− 0.801~ − 0.593)), and hemoglobin (r= − 0.589(− 0.716~ − 0.419)) (all P< 0.001). Multivariate regression identified kidney injury (OR=17.75, 95% CI 3.63‑86.97, P< 0.001) and reduced hemoglobin (OR=0.93, 95% CI 0.89‑0.98, P=0.005) as independent correlates. ANA positivity reached significance in multivariate analysis (OR=7.30, 95% CI 1.13‑47.37, P=0.038), but this result should be interpreted cautiously due to small sample and wide confidence intervals.Conclusion: In this single‑center retrospective MPO‑AAV cohort, renal injury and lower hemoglobin were independently associated with higher cross‑sectional disease activity.Keywords: vasculitis, ANCA, disease activity, renal function, anemia, antinuclear antibodies
Tsui Chi Mak,1 Celine Cinlin Tang,1 Jenny Man Chik Choi,1 Karlen Ka Pui Law,1 Angie Yuen Kiu Wong,1 Kenney Ki Lee Lau21Department of Occupational Therapy, Duchess of Kent Children’s Hospital, Hong Kong, People’s Republic of China; 2Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People’s Republic of ChinaCorrespondence: Kenney Ki Lee Lau, Email kenney.kl.lau@link.cuhk.edu.hkBackground: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease causing progressive joint damage, disability, and excess mortality. Evaluating long-term epidemiological trajectories across high-resource health systems is essential for optimizing rheumatology care. This study analyzes the burden and 33-year temporal trends of RA across high-income countries and territories using Global Burden of Disease (GBD) Study 2023 estimates.Methods: We analyzed incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) across 36 high-income countries and territories (5 GBD regions: Australasia, High-income Asia Pacific, High-income North America, Southern Latin America, and Western Europe) from 1990 to 2023. To distinguish clinical risk from population growth and aging, we prioritized age-standardized rates (ASRs per 100,000) alongside absolute metrics. We present all estimates with 95% uncertainty intervals (UIs).Results: In 2023, high-income settings accounted for 0.26 million incident cases, 4.98 million prevalent cases, 0.80 million DALYs, and 10,190 deaths. From 1990 to 2023, absolute prevalent cases (+72%) and DALYs (+49%) grew substantially due to demographic aging. Conversely, underlying age-standardized incidence (17.12 [95% UI: 15.69– 18.83]) and prevalence (282.80 [95% UI: 256.24– 314.48]) increased modestly (+9% and +10%), while age-standardized DALY rates (44.14 [95% UI: 32.63– 56.59]) fell by 7% and age-standardized death rates (0.39 [95% UI: 0.34– 0.45]) decreased markedly by 41%. Australasia exhibited the highest ASRs across all metrics in 2023, whereas Southern Latin America demonstrated the sharpest ASR increases (+54% incidence, +62% prevalence, +34% DALYs). High-income Asia Pacific achieved the largest ASR reductions (− 14% incidence, − 12% prevalence, − 26% DALYs, − 49% deaths). Females and adults aged over 60 years consistently bore the primary disease burden.Conclusion: While age-standardized mortality has dropped substantially, reflecting improved management of RA and its comorbidities, the non-fatal disability burden continues to expand alongside population aging. Rheumatology health services must shift toward long-term disability management, early treat-to-target intervention, and addressing persistent regional disparities.Keywords: rheumatoid arthritis, global burden of disease, epidemiology, high-income countries
Agnes King Yan Lam,1 Karlen Ka Pui Law,2 Kenney Ki Lee Lau31Department of Physiotherapy, North District Hospital, Hong Kong, People’s Republic of China; 2Department of Occupational Therapy, Duchess of Kent Children’s Hospital, Hong Kong, People’s Republic of China; 3Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong, People’s Republic of ChinaCorrespondence: Kenney Ki Lee Lau, Email kenney.kl.lau@link.cuhk.edu.hkBackground: Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases worldwide and is characterized by chronic pain and functional decline, particularly among older adults. High body mass index (BMI) is a key modifiable risk factor associated with OA and may influence OA burden through biomechanical and metabolic pathways. This study aimed to assess the regional and national burden of OA attributable to high BMI in the Western Pacific Region from 1990 to 2023.Methods: This ecological secondary data analysis used Global Burden of Disease (GBD) 2023 data to quantify the burden of OA across 31 countries in the Western Pacific Region. Combined OA was defined as the sum of the burdens of hip and knee OA, and site-specific estimates for hip and knee OA were reported separately. Within the GBD comparative risk assessment framework, we estimated risk-attributable OA burden using the relevant population attributable fractions. We estimated years lived with disability (YLDs) using the GBD modeling pipeline and applied age standardization to enable comparisons across populations. We quantified uncertainty by generating 250 model draws to obtain mean estimates and 95% uncertainty intervals (UIs), defined as the 2.5th and 97.5th percentiles of the draws.Results: In 2023, the Western Pacific Region was estimated to have 1.55 million YLDs attributable to high BMI for combined OA, a 287% increase since 1990. The age-standardized YLD rate for combined OA in 2023 was 46.68 (95% UI: − 0.47 to 124.21) per 100,000 population, reflecting a marked 58% increase (95% UI: 28% to 103%) from 1990. The highest age-specific rate of YLDs per 100,000 population were observed in the 70– 74 years age group for combined OA [203.63 (95% UI: − 2.02 to 549.41)], the 65– 69 years age group for knee OA [191.51 (95% UI: − 1.76 to 514.58)] and 80– 84 years age group for hip OA [14.85 (95% UI: − 0.17 to 42.17)]. Females had higher age-standardized YLD rates for both combined and knee OA. At the national level, the five countries with the highest age-standardized YLD rates attributable to high BMI for combined OA in 2023 were the Cook Islands, American Samoa, Niue, Tonga, and Nauru.Conclusion: The estimated number and rate of YLDs attributable to high BMI for OA showed a consistent upward trend over the study period in the Western Pacific Region. These findings highlight the substantial public health burden of OA associated with high BMI. Region-specific surveillance, prevention, policy, and management strategies targeting overweight/obesity are needed to reduce the OA burden in the Western Pacific Region.Keywords: osteoarthritis, high body mass index, global burden of disease, western pacific region, epidemiology
Ibrahim A Al-Homood,1,* Sarah Binhassan,2,* Khalid AlMatham,3 Lena M Hassen,4,5 Manar Samman61Rheumatology Section, Medical Speciality Department, King Fahad Medical City, Riyadh, Saudi Arabia; 2Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 3Nephrology Section, Medical Speciality Department, King Fahad Medical City, Riyadh, Saudi Arabia; 4Zoology Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia; 5Rheumatology Unit, Department of Medicine, College of Medicine, King Saud University Medical City, Riyadh, Saudi Arabia; 6Lab Operation, Health Support Services Centre, Ministry of Health, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Ibrahim A Al-Homood, Rheumatology Section, Medical Speciality Department, King Fahad Medical City, Riyadh, Saudi Arabia, Email iaalhomood@kfmc.med.saObjective: To identify novel candidate gene variants and investigate their role in a cohort of Saudi patients with Systemic Lupus Erythematosus (SLE). In addition, evaluate their distribution relative to common risk loci identified in the NHGRI-EBI GWAS Catalog.Methods: Whole Exome Sequencing (WES) was performed on the extracted genomic DNA for 29 patients with confirmed SLE. Descriptive analyses were used to summarize the patients’ characteristics. Variant prioritization was initiated through a manual clinical interpretation according to ACMG guidelines, followed by a multi-step filtering pipeline to identify rare, high-impact candidates (gnomAD MAF < 1%, CADD > 20). The statistical analysis was conducted using R software R version 4.4.2 and several specialised packages.Results: The analysis revealed an exploratory "multi-hit” genetic landscape. Notable candidate variants were identified in genes related to DNA damage response (ATM, BRCA1) and membrane integrity (DYSF, USH2A). NPFFR2 emerged as a recurrently variant candidate gene (24% of the cohort). Phenotypic partitioning suggested that NPFFR2 variant may be associated with a distinct neuro-musculoskeletal profile; 85.7% of carriers exhibited musculoskeletal involvement. Conversely, carriers showed a marginal inverse trend with oral ulcers (P = 0.093), and NPFFR2 variant showed a potential trend toward mutual exclusivity with haematological involvement (P = 0.066), suggesting carriers may be less likely to present with either mucocutaneous or haematological manifestations. These findings suggest a hypothesis-generating neuro-immune model for SLE, where rare variants may influence disease expression toward specific organ systems.Conclusion: This study highlights the presence of rare, candidate variants in a Saudi SLE cohort that are distinct from common GWAS-identified loci. These findings suggest that SLE clinical heterogeneity may be influenced by specific genetic endotypes. Our observations open the door for a preliminary roadmap for precision medicine and the identification of potentially treatment-refractory patients.Keywords: systemic lupus erythematosus, SLE, whole exome sequencing, WES, NPFFR2 variant, drug resistance
