Prevalence Of Rheumatoid Arthritis Research Articles

2023 Management Recommendations of Bangladesh Rheumatology Society on Pharmacological Treatment of Rheumatoid Arthritis With Synthetic and Biologic Disease-Modifying Drugs.

Rheumatoid arthritis (RA) is the most common inflammatory polyarthritis in Bangladesh. Bangladesh Rheumatology Society (BRS) proposes these management recommendations to treat the considerable burden of RA in the resource-constrained situation based on the best current evidence combined with societal challenges and opportunities.BRS formed a task force (TF) comprising four rheumatologists. The TF searched for all available literature, including updated American College of Rheumatology (ACR), European Alliance of Associations for Rheumatology (EULAR), and Asia-Pacific League of Associations for Rheumatology (APLAR) and several other guidelines, and systematic literature reviews until October 2023, and then a steering committee was formed, which included rheumatologists and internists. We followed the EULAR standard operating procedures to categorize levels of evidence and grading of recommendations. This recommendation has two parts -- general (diagnosis of RA, nomenclature of disease-modifying anti-rheumatic drugs [DMARDs], disease activity indices) and management portion. The TF agreed on four overarching principles and 12 recommendations. Overarching principles deal with early diagnosis and disease activity monitoring. Recommendations 1-5 discuss using glucocorticoids, NSAIDs, and conventional synthetic DMARDs (csDMARD). Recommendations 6-9 stretch the use of targeted synthetic DMARDs (tsDMARDs) and biological DMARDs (bDMARDs). The suggested DMARD therapy includes initiation with methotrexate (MTX) or another csDMARD (in case of contraindication to MTX) in the first phase and the addition of a tsDMARD in the second phase, switching to an alternative tsDMARDs or bDMARDs in the subsequent phases. The TF included the Padua prediction score for the thromboembolism risk estimation. Recommendations 10-12 cover infection screening, vaccination, and DMARD tapering. Bangladesh has a higher prevalence of RA. This recommendation will serve as a tool to treat this high burden of patients with RA scientifically and more effectively.

Rheumatoid arthritis epidemiology: a nationwide study in Poland

To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013–2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients’ gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.

Global burden of rheumatoid arthritis among adolescents and young adults aged 10-24 years: A trend analysis study from 1990 to 2019.

In recent decades, there has been a global increase in the burden of rheumatoid arthritis (RA) among adolescents and young adults (AYAs), making it a significant public health issue. However, our understanding of the disease burden, harm, and influencing factors of RA in this population remains insufficient. This study aimed to assess the trends in RA burden among AYAs aged 10-24 years from 1990 to 2019 at the global, regional, and national levels. Incidence, prevalence, and disability-adjusted life years (DALYs) rate per 100,000 population, as well as average annual percentage changes (AAPCs), of RA among individuals aged 10-24 years were reported globally, regionally, and nationally based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019). These global trends were further analyzed by age, sex, and Sociodemographic index (SDI). Joinpoint regression analysis was used to determine the year in which the most significant changes in global trends occurred. Globally, the incidence of RA among AYAs increased from 4.98 per 100,000 population in 1990 to 5.41 per 100,000 population in 2019, with an AAPCs of 0.29 (95%CI: 0.26, 0.32, p < 0.001). The most significant increase occurred in 2000, while the most significant decrease occurred in 2014. The prevalence increased from 34.11 per 100,000 population in 1990 to 36.34 per 100,000 population in 2019, with an AAPCs of 0.22 (95%CI: 0.19, 0.24, p<0.001); The most significant increase was observed in 2000, and the most significant decrease occurred in 2014. DALYs rate with RA were 5.96 per 100,000 population in 1990 and 5.79 per 100,000 population in 2019 for AYAs, with an average decrease of 0.1 years per year (AAPCs = -0.1, 95%CI: -0.2, -0.01, p = 0.04). In terms of gender, the incidence, prevalence, and DALYs rate were higher for females compared to males during the same period. Regarding age, the incidence, prevalence, and DALYs rate increased with increasing age. Based on the SDI quintile, the incidence, prevalence, and DALYs rate of RA were highest in countries with high SDI and lowest in countries with low SDI from 1990 to 2019. However, the relationship between incidence and SDI is non-linear. In terms of regions, Tropical Latin America exhibited the highest incidence, prevalence, and DALYs rate, while Andean Latin America experienced the most rapid increase in incidence and prevalence. Southern Latin America saw the fastest growth in DALYs rate, whereas Southern Sub-Saharan Africa witnessed the most significant decline. In conclusion, the study revealed an overall increase in the incidence and prevalence of RA among adolescents and young adults (AYAs) over the past three decades, while DALYs rate remained relatively stable. Furthermore, the incidence, prevalence, and DALYs rate of RA were found to increase with age. Fortunately, recent proactive preventive measures and treatment methods have shown promising results. Moving forward, it is crucial to prioritize the female population and AYAs patients in order to further alleviate the global burden of RA.

Association between oxidative balance score and rheumatoid arthritis in female: a cross-sectional study

ObjectiveAlthough oxidative stress is a recognized factor of inflammation, the correlation between oxidative balance score (OBS), a biomarker indicating the balance of oxidation and antioxidant, and rheumatoid arthritis (RA), an immune system disease that tends to occur in women, remains unexplored. Hence, the aim of this study was to investigate the potential association between OBS and RA in women.MethodsObservational surveys were performed by employing information extracted from the National Health and Nutrition Examination Survey (NHANES) for the period 2007–2018. Various statistical techniques were employed to investigate the association between OBS and RA, encompassing multivariable logistic regression analysis, subgroup analyses, smooth curve fitting, and threshold effect analysis.ResultsThe study included 8219 female participants, including 597 patients with RA. The results showed that higher Total OBS (TOBS) significantly correlated with lower RA prevalence in the entirely modified model [odd ratio (OR) = 0.968; 95% confidence interval (CI) = 0.952 to 0.984; P = 0.0001]. Dietary OBS (DOBS) and lifestyle OBS (LOBS) also negatively correlated with RA. This association was remarkably consistent across TOBS subgroups by age, race, education level, family poverty-to-income ratio (PIR), hypertension and diabetes. Smooth curve fitting and threshold effect analysis also revealed the linear relationship between OBS and RA.ConclusionsOverall, OBS was negatively associated with RA in female. This study suggested that an antioxidant diet and lifestyle may be promising measures to prevent RA in female.

Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study.

To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). This population-based cohort study utilised Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within one year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes, and corticosteroids). Modified Poisson regression models with robust variance estimated risk ratios and 95% confidence intervals (RR 95%CI). We included 1,007 births (453 exposed) and 2,500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed, and unexposed groups were 3.6%, 3.7%, and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6%, and 4.3%, respectively. The adjusted RRs (95%CI) were 1.29 (0.65-2.56) in the SLE cohort, 1.32 (0.56-3.13) in the RA cohort, and 1.30 (0.76-2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings. First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy.

Comorbidity clusters in patients with rheumatoid arthritis identify a patient phenotype with a favourable prognosis

ObjectivesWe aimed to cluster patients with rheumatoid arthritis (RA) based on comorbidities and then examine the association between these clusters and RA disease activity and mortality.MethodsIn this population-based study, residents...

Is occupational noise associated with arthritis? Cross-sectional evidence from US population

BackgroundThe impact of occupational noise exposure on various diseases, including ear and cardiovascular diseases, has been studied extensively. Nevertheless, the connection between osteoarthritis (OA) and rheumatoid arthritis (RA) and occupational noise exposure remains largely unexplored in real-world scenarios. This study assessed the association between occupational noise exposure and the prevalence of two types of arthritis.MethodsThis study used database data from 2005 to 2012 and 2015–March 2020 from the prepandemic National Health and Nutrition Examination Survey (NHANES) related to occupational noise exposure and arthritis. Multivariate logistic regression analysis was used to estimate the association between occupational noise exposure and RA/OA, adjusting for age, gender, race, education level, marital status, the ratio of family income to poverty, trouble sleeping, smoking status, alcohol consumption, diabetes, hypertension, body mass index (BMI), metabolic equivalents (METs), and thyroid disease.ResultsThis study included 11,053 participants. Multivariate logistic regression analysis demonstrated that previous exposure to occupational noise was positively associated with self-reported RA (OR = 1.43, 95% CI = 1.18–1.73) and OA (OR = 1.25, 95% CI = 1.07–1.46). Compared to individuals without a history of occupational noise exposure, those with an exposure duration of 1 year or greater exhibited higher odds of prevalent RA, though there was no apparent exposure response relationship for noise exposure durations longer than 1 year. The results of our subgroup analyses showed a significant interaction between age and occupational noise exposure on the odds of self-reported prevalent OA.ConclusionsOur findings suggest an association between occupational noise exposure and the prevalence of RA and OA. Nevertheless, further clinical and basic research is warranted to better explore their associations.

Associations of cereal fiber intake with rheumatoid arthritis mediated by dietary inflammatory index: insights from NHANES 2011–2020

Rheumatoid Arthritis (RA) is an increasingly prevalent inflammatory disorder worldwide. Its complex etiology has recently brought dietary factors, particularly fiber intake, into focus as potential influencers. Our study investigates the intricate relationship between various sources of dietary fiber and RA, emphasizing the mediating role of the Dietary Inflammatory Index (DII). Leveraging data from the National Health and Nutrition Examination Survey spanning 2011 to 2020. We meticulously assessed dietary fiber intake through dual 24 h dietary recall interviews, while RA diagnoses were established based on comprehensive medical surveys. The relationships between fiber intake, RA prevalence, and DII mediation were analyzed using sophisticated multivariate logistic regression and mediation analysis. Among our study cohort, 7% were diagnosed with RA. We observed a notable inverse correlation between increased total fiber intake, particularly 5 g/day increments, and the incidence of RA, with cereal fiber intake emerging as the primary mitigating factor. Intriguingly, the DII played a significant role in mediating this association, especially regarding cereal fiber. Our findings reveal a significant association between higher cereal fiber consumption and a reduced prevalence of RA. Additionally, the DII stands out as a pivotal mediator in this relationship, highlighting dietary management's critical role in preventing and managing RA.

Comprehensive Review Of Rheumatoid Arthritis: Insights, Challenges, And Prospects

This comprehensive review explores the multifaceted landscape of rheumatoid arthritis (RA), encompassing its epidemiology, pathophysiology, clinical manifestations, diagnosis, treatment approaches, and the impact on patients' quality of life. The review delves into the global prevalence of RA, demographic patterns, and associated risk factors, shedding light on the complex interplay of genetics, immunology, and environmental triggers in disease development. The pathophysiological mechanisms involving immunological dysregulation, genetic factors, and environmental triggers are elucidated, providing a foundation for understanding the intricate processes driving RA. Detailed insights into the clinical manifestations of RA, including joint involvement, extra-articular manifestations, and the progression of the disease, are provided. The diagnostic landscape is explored, covering the ACR/EULAR classification criteria, diagnostic imaging, and laboratory tests that facilitate accurate and timely identification of RA. Treatment approaches, from pharmacological therapies like DMARDs and biologics to non-pharmacological interventions such as physical and occupational therapy, emphasizing a holistic management strategy. The economic burden of RA, its impact on healthcare utilization, and the broader societal implications are scrutinized, providing valuable insights into the challenges faced by both individuals and healthcare systems. Prevention and disease management strategies are highlighted, emphasizing the importance of early intervention, patient education, and public health initiatives in mitigating the impact of RA. Current challenges in RA management are outlined, with proposed future research directions aimed at advancing understanding and treatment.

Comparative Study to Assess the Safety and Effectiveness of Methotrexate and Tofacitinib in Patients Diagnosed with Rheumatoid Arthritis

Introduction: Rheumatoid Arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints resulting in pain and disability. The prevalence of RA is estimated to be 1% to 2% globally and does not have any ethnic or racial differences. Elevated C-Reactive Protein (CRP) levels in the blood indicate the presence of inflammation and can be used to detect and monitor the disease. Patients with RA tend to have a significant load in association with pain, disability and activity limitation which in turn affects the Health-Related Quality of Life. With a growing rate of RA globally there is a need to assess the safety and effectiveness of drugs and provide a suitable treatment to improve the quality of life of the patients. OBJECTIVES: The goal of the study was to compare the safety and effectiveness of Tofacitinib and Methotrexate in patients diagnosed with Rheumatoid Arthritis. The study also aimed to assess the Health-Related Quality of Life (HRQOL) of patients. Methodology: This was an observational study conducted in selected Orthopaedic clinics in T. Dasarahalli Bengaluru. All the subjects (n=40) meeting the inclusion and exclusion criteria were briefed about the purpose of the study and the informed consent was obtained. The subject’s demographic details and responses were collected. Standard questionnaires, 36-Item Short Form survey (SF-36) to assess the HRQOL and Health Assessment Questionnaire-Disease Index (HAQ-DI) to assess the effectiveness of the drugs were used in all patients. The collected data were entered in Microsoft Excel and appropriate descriptive and statistical analysis was performed. Results: A total of 40 samples were enrolled in the study based on Inclusion and Exclusion criteria. Out of which 50% of the participants were on Methotrexate (MTX) and the other 50% were on Tofacitinib. Majority of the subjects in the study were women (90%) and men (10%) with mean age 51 and 54 respectively. On comparing the effectiveness of both

National burden of rheumatoid arthritis in Canada, 1990–2019: findings from the Global Burden of Disease Study 2019 – a GBD collaborator-led study

ObjectiveThe objectives of this study were: (1) to describe burden of rheumatoid arthritis (RA) and trends from 1990 to 2019 using the Global Burden of Diseases, Injuries and Risk Factors...

An Updated Review on Rheumatoid Arthritis (RA): Epidemiology, Pathophysiology, Diagnosis, and the Current Approaches for Its Treatment

Rheumatoid arthritis (RA) is a systemic self-inflicted inflammatory disease that primarily affects middle-aged women. Globally, 1% of people live with RA. This review aims to provide updated information on the different aspects of RA, including its epidemiology, pathophysiology, diagnosis, treatment, and management. A web-based literature search was conducted through various databases, including PubMed, Google Scholar, and Science Direct, to identify the most relevant studies. Epidemiological studies have suggested that the prevalence and occurrence of RA have remained inconsistent across geographical areas in different periods. Many factors such as age, gender, inheritances, and environmental exposure can contribute to the severity of the disease. The acute form of RA usually presents with pain, and if left untreated, it can result in joint deformities and influence a patient’s quality of life (QoL). RA diagnosis is usually based on the manifestation of pain with inflammation. Currently, many therapeutic strategies are available for the cure of RA. The management of daily routine activities is required with treatment to curtail the damage, avoid future deformities, and ultimately minimize the aching trouble of the patient.

EPIGENETIC AGING AND RHEUMATOID ARTHRITIS

Abstract Indicators of biological aging with rheumatoid arthritis (RA), a chronic autoimmune disease, are not yet fully known. In this cross-sectional study, we tested associations between plasma indicators of epigenetic aging using online data (GSE42861) regarding RA and DNA methylation from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Peripheral blood DNA methylation of participants 18-70 years old was assessed using Illumina HumanMethylation450 arrays. Horvath’s online DNA Methylation Age Calculator determined DNAm estimate of Telomere length (DNAmTL), Hannum’s, Horvath’s 2013 and 2018 epigenetic ages, PhenoAge and GrimAge and the respective age accelerations. Association of RA prevalence with epigenetic age were determined using linear regression, correcting for false discovery rate. We identified significant associations of RA with age acceleration measures of Horvath 2013 (Estimate:-1.34 ; FDR p-value: 1.0 × 10-2) and Horvath 2018 (Estimate:-1.32; FDR p-value: 4.0 × 10-5), extrinsic age acceleration (Estimate: 1.34 ; FDR p-value: 1.0 × 10-2), PhenoAge acceleration (Estimate: 2.31; FDR p-value: 1.1 × 10-5), GrimAge (Estimate: 2.54; FDR p-value: 1.0 × 10-2) and GrimAge acceleration (Estimate: 3.15 ; FDR p-value: 1.7 × 10-17), adjusting for sex and smoking (FDR p-value&amp;lt;=0.05). In sex stratified analyses, first-generation clocks were associated only in women, but no sex specific effects for PhenoAge or GrimAge accelerations were identified. The second generation ‘biological’ clocks PhenoAge, GrimAge and its components showed higher epigenetic age acceleration in RA cases compared to healthy controls. We conclude that second generation indicators of epigenetic aging provide promise as markers of biological aging in people with RA.

Health and economic burden of low back pain and rheumatoid arthritis attributable to smoking in 192 countries and territories in 2019.

Smoking is a risk factor for low back pain (LBP) and rheumatoid arthritis (RA). We aimed to estimate the global health and economic burden of LBP and RA attributable to smoking. This was a cross-sectional study. The study was conducted in 192 countries and territories. Prevalent cases of LBP and RA were used, extracted from the Global Burden of Diseases, Injuries and Risk Factors Study 2019 data repositories. Smoking-attributable health and economic burden was estimated with the population-attributable fraction method. Smoking-attributable prevalence of LBP and RA and health-care costs were estimated for patients of all ages, whereas years lived with disability (YLDs) and productivity losses due to morbidity were estimated for patients aged 15-84 years. Uncertainty intervals (UIs) of the results were obtained by repeating the analysis with the lower and upper bounds of all input variables. Globally, smoking accounted for 84.5 million (UI = 56.7-120.2 million) prevalent cases of LBP, 1.8 million (UI = 0.5-3.4 million) prevalent cases of RA and 11.3 million (UI = 6.2-18.5 million) YLDs, which represented 1.5% of all-cause YLDs in the working-age population aged 15-84 years in 2019. Health-care costs and productivity losses of smoking-attributable LBP and RA cost the global economy purchasing-power parity $326.0 billion (UI = $184.0-521.4 billion), representing 0.2% of the global gross domestic product. Specifically, smoking accounted for $65.8 billion (UI = $38.0-101.2 billion) in health-care costs world-wide, with more than half [$39.8 billion (UI = $23.1-61.3 billion), 60.6%] borne by the public sector. Smoking also contributed to $260.3 billion (UI = $146.0-420.3 billion) in productivity losses globally. Approximately 60.0% of the global YLDs were observed in middle-income countries, whereas 84.4% of health-care costs and 72.7% of productivity losses were borne by high-income countries. Globally, in 2019, smoking accounted for more than 11.0 million years lived with disability and purchasing-power parity $326.0 billion in economic losses due to low back pain and rheumatoid arthritis. Middle-income countries suffered more morbidity, whereas high-income countries experienced larger economic losses.

Capturing Patient Value in an Economic Evaluation.

Economic evaluations predominantly use generic outcomes, such as the Euro Quality of Life-5 Dimension (EQ-5D), to assess health status. However, because of the generic nature, they are less suitable to capture the quality of life of patients with specific conditions. Given the transition to patient-centered (remote) care delivery, this study aims to evaluate the possibility of using disease-specific measures in a cost-effectiveness analysis. A real-life cohort from Maasstad Hospital (2020-2021) in the Netherlands, with 772 patients with rheumatoid arthritis (RA), was used to assess the cost-effectiveness of electronic consultations (e-consultations) compared with face-to-face consultations. The Incremental Cost-Effectiveness Ratio (ICER), based on the generic EQ-5D, was compared with ICER's based on RA-specific measures: the Rheumatoid Arthritis Impact of Disease (RAID) and Health Assessment Questionnaire-Disability Index (HAQ-DI). To compare the cost-effectiveness of these different measures, HAQ-DI and RAID were expressed in quality-adjusted life-years (QALYs) via estimated conversion equations. Disease-specific patient-reported outcome measures (PROMs) offer a promising alternative for traditional measures in economic evaluations, capturing patient-relevant domains more comprehensively. Because PROMs are increasingly applied in clinical practice, the next step entails modeling of an RA patient-wide conversion equation to implement PROMs in economic evaluations. The conventional ICER (eg, EQ-5D) indicates that e-consultations are cost-effective with cost savings of -€161,000 per QALY gained for a prevalent RA cohort treated in a secondary trainee hospital. RA-specific measures show similar results, with ICERs of -€163,000 per HAQ-DI (QALY) and -€223,000 per RAID (QALY) gained. RA-specific measures capture patient-relevant domains and offer the opportunity to improve the assessment and treatment of the disease impact.

A stronger association of depression with rheumatoid arthritis in presence of obesity and hypertriglyceridemia.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic and systemic inflammation. Recent research underscores the role of chronic inflammation in multiple common RA comorbidities such as depression, obesity, and cardiovascular diseases (CVDs), suggesting a potential overlap of the pathogenic mechanisms for RA. However, it is not well understood how the coexistence of these comorbid conditions impacts the risk of RA and whether any such association relates to body's inflammatory state. We used data from the 2007-2010 United States National Health and Nutrition Examination Survey (NHANES) database and compared RA prevalence between subsamples with the presence of any two conditions among depression, obesity, and hypertriglyceridemia (HTG). Each subsample was further divided into three categories based on the serum level of the inflammatory marker C-reactive protein (CRP) and analyzed for statistically significant differences using three-way χ2 tests of independence. The study was conducted on 4,136 patients who fulfilled the inclusion criteria (representing 163,540,241 individuals after adjustment for sampling weights). Rates of depression, obesity, and HTG were found to be significantly higher (P < 0.001) among the subjects with RA compared with the control population with no arthritis. The presence of depression along with obesity or HTG showed a noticeably higher RA prevalence but such an association was not observed for the combination of obesity and HTG. The synergistic effect of HTG with depression was found to be most prominent at a medium CRP level (1-3 mg/L), while for obesity, the effect was observed across all CRP levels examined. These findings were further confirmed by the three-way χ2 test for independence. The presence of obesity or HTG in subjects suffering from depression might pose an increased risk of RA. Inflammatory mechanisms potentially play an important underlying role as suggested by the strong dependency of the association to CRP level. Identification of synergistic associations between RA risk conditions could provide useful information to predict the development and progress of RA.

Clonal Hematopoiesis Associated with Rheumatoid Arthritis

Introduction: Clonal hematopoiesis (CH) becomes common with age and can play a role in the pathophysiology of inflammatory diseases by modifying immune cell function. CH is characterized by the presence of somatic mutations in genes such as DNMT3A and TET2 (CH of indeterminate potential, CHIP), and as mosaic chromosomal alterations (mCAs). While CHIP, particularly in the context of TET2 mutations, can promote inflammation in cardiovascular diseases, the association between clonal hematopoiesis and autoimmunity has not been comprehensively studied to date. Rheumatoid arthritis (RA) is one of the most common autoimmune diseases primarily affecting joints. Seropositive RA is defined by the presence of anti-cyclic citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF), whereas seronegative RA is a more heterogeneous inflammatory disease entity involving patients with clinical RA manifestations in the absence of ACPA and RF. Understanding of the association between CH and inflammatory processes may yield novel insights into prevention and management of autoimmune diseases. Methods: To comprehensively evaluate the association between CH and autoimmune diseases, we identified CHIP variants in whole exome sequencing (WES) data from the FINRISK study (N=10 129). We also detected mCAs and CHIP in the nationwide FinnGen study (N=340 173), where we manually identified CHIP carriers as outliers in SNP intensity plots at known CHIP loci in DNA microarray data. Only known CHIP loci with variant prevalence comparable to UK Biobank WES data and significant positive associations with age and hematological malignancies were included for downstream analyses. To further characterize the link between CHIP and RA phenotypes, we performed targeted panel sequencing of 69 myeloid driver genes in 675 RA patient blood samples (91% collected at diagnosis) and 60 healthy controls. We studied the association between CH and RA in multivariable models excluding participants with prevalent hematologic malignancies and adjusting for sex, age, smoking, and principal components of ancestry. We performed uni- and multivariable analyses to evaluate the link between CHIP and RA patient phenotypes. Results: We identified CHIP in 381 (3.8%) FINRISK participants. As expected, the prevalence of CHIP increased with age, and CHIP variants were associated with prevalent and incident hematologic malignancies. C-reactive protein values were higher in participants with CHIP (P&amp;lt;0.001). In multivariable models, CHIP status (OR 1.98, 1.13-3.45, P=0.017) was more common in participants with questionnaire-based history of RA (N=151) (Fig 1A). In the FinnGen study, CHIP carrier status was associated with prevalent autoimmune diseases (OR 1.26, 1.05-1.53, P=0.015). We validated the association between prevalent RA (N=10 990) and CHIP carrier status (N=2 393) in the FinnGen study (OR 1.58, 1.18-2.13, P=0.002) (Fig 1A). In particular, CHIP (OR 2.17, 1.40-3.36, P&amp;lt;0.001), and GNB1 variants (OR 4.71, 1.87-11.82, P=0.001) were associated with the seronegative RA, whereas DNMT3A was associated with seropositive RA (OR 1.83, 1.08-3.09, P=0.024). We observed no association between autosomal mCAs and RA. Using targeted panel sequencing, we found CHIP in 22% (146/675) of RA patients. RA patients with CHIP variants were older than those without a CHIP variant (median, 69 vs 63 years, P&amp;lt;0.001). Erythrocyte sedimentation rate (ESR) was higher in those with CHIP (median, 42.5 vs 26.0 mm/h, P=0.043). RA patients with TET2 variants were more likely to have seronegative disease compared with TET2 wild-type patients (proportion of seronegative patients, 56% vs 33%, OR 2.62; P=0.008) (Fig 1B). The association remained significant (OR 2.38, 1.14-4.96, P=0.02) when adjusting for age, sex, and smoking. Evaluation of longitudinal disease outcomes by CHIP status are currently ongoing. Conclusion: CHIP variants were more common in participants with prevalent RA in two population-level cohorts, and the association was specific to seronegative RA in the large FinnGen cohort. In newly diagnosed RA patients, TET2 mutations were more common in seronegative than in seropositive RA. While the causality and the functional basis of these observations remain to be explored in future studies, our results provide additional evidence for the association between CHIP and inflammation in various disease contexts, including autoimmune diseases.

National trends in rheumatoid arthritis and osteoarthritis prevalence in South Korea, 1998–2021

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and βdiff (β difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005–2007 to 1.55% in 2016–2019 and OA: from 9.75% in 2005–2007 to 8.27% in 2016–2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19–60 years, ratio of ORs: 1.222; 95% CI 1.011–1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007–1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119–1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence.

Is rheumatoid arthritis a neglected comorbidity in neurofibromatosis type 1?

Aims: Neurofibromatosis type 1 (NF-1) is a relatively rare disorder with autosomal dominant inheritance. Despite current reports highlighting the association between NF-1 and some rheumatic diseases (e.g., systemic lupus erythematosus, juvenile idiopathic arthritis, ankylosing spondylitis, and antiphospholipid antibody syndrome), the literature seems to have missed focusing on its relationship with rheumatological disorders. Hence, the present study attempted to explore definite NF-1 molecular genetic mutation in association with accompanying rheumatic diseases, particularly rheumatoid arthritis.&#x0D; Methods: The patients (n=23) aged 18 years who were diagnosed with NF-1 genetic mutation between 2010-2022 in the medical genetics department of our university were recruited for medical examination regarding rheumatic disorders in our rheumatology outpatient clinic. &#x0D; Results: There were a total of 23 patients in this study, 14 (60.9%) males and 9 (39.1%) females, with a mean age of 27.4±9.2 years (18-51 years). As a result, 4 (17.3%) patients were diagnosed with rheumatoid arthritis (RA), 3 with seropositive RA, and one with seronegative RA. Of the diagnoses, two were established RA, and two were early RA. All patients with RA had a positive metacarpophalangeal joint (MCP) squeeze test and experienced pain in bilateral hands and wrists and morning stiffness for more than 45 min.&#x0D; Conclusion: While the community prevalence of RA is about 1%, it is noteworthy that we detected RA in 17.3% of our patients. In the follow-up of patients with NF-1, routine examinations for pain in bilateral hands and wrists, morning stiffness over 45 minutes, and positivity of the MCP squeeze test are thought to allow early diagnosis of RA and, thus, relevant therapies.

The association of milk products with rheumatoid arthritis: A cross-sectional study from NHANES

ObjectiveMilk products are a major part of the western diet, but the role of their effect in rheumatoid arthritis (RA) is controversial. The objective of this study was to explore the relationship between milk products and RA in the United States (US) population. MethodsIn the cross-sectional study, a total of 12,813 participants aged 20years or older were selected from the National Health and Nutrition Examination Survey (NHANES). Consumption of milk products was collected by personal interview, and RA status was obtained by self-reported questionnaires. The association between milk products and RA was estimated by using the weighted logistic regression model. ResultsWe found a negative association of once a day or more milk products intake with self-reported RA prevalence (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.53 to 0.86; P<0.001). A linear trend between consumption of milk products and the prevalence of RA (P<0.01) was also observed. In subgroup analysis, protective effects of milk products on RA were more pronounced in several groups (i.e., Mexican Americans, highly educated and drinking individuals, etc.). However, no interaction effect of stratification variables and the frequency of milk products intake with RA was detected. After imputing missing data, the sensitivity analysis showed the same association. ConclusionThis study suggested a negative association between consumption of milk products and RA among US population. Further investigations are warranted to validate the causal association and the underlying mechanism.