Outcomes In Rheumatoid Arthritis Research Articles

Polypropylene sulfide methotrexate nanoparticles target the synovial lymphatic system to restore immune tolerance in rheumatoid arthritis

Around 40 % of patients fail to achieve primary clinical outcomes for rheumatoid arthritis (RA). The growth of lymphatic system in the synovial membrane, is a primary response during RA inflammation. It is suggested that a delivery strategy targeting immunosuppressive agents to the synovial lymph nodes and then to the immune cells is beneficial for resolving arthritis. This study introduced a synthetic polypropylene sulfide methotrexate nano-delivery system (PPS-MTX), which was prepared by covalently bonding methotrexate to polypropylene sulfide, with a diameter size range of 36 nm. It enhanced joint accumulation and retention, which can be selectively uptake by antigen-presenting cells in the synovial lymphatic system. The results indicated that PPS-MTX nanoparticles effectively improved arthritis disease progression and restored the immune tolerance microenvironment in the synovial lymphatic system, promoting peripheral tolerance in collagen-induced arthritis mice. Additionally, no systemic toxicity was observed. This study presents a promising targeted strategy for inducing immune tolerance in the treatment of rheumatoid arthritis.

Leveraging large-scale genetic data to assess the causal impact of COVID-19 on multisystemic diseases

BackgroundThe long-term impacts of COVID-19 on human health are a major concern, yet comprehensive evaluations of its effects on various health conditions are lacking.MethodsThis study aims to evaluate the role of various diseases in relation to COVID-19 by analyzing genetic data from a large-scale population over 2,000,000 individuals. A bidirectional two-sample Mendelian randomization approach was used, with exposures including COVID-19 susceptibility, hospitalization, and severity, and outcomes encompassing 86 different diseases or traits. A reverse Mendelian randomization analysis was performed to assess the impact of these diseases on COVID-19.ResultsOur analysis identified causal relationships between COVID-19 susceptibility and several conditions, including breast cancer (OR = 1.0073, 95% CI = 1.0032–1.0114, p = 5 × 10 − 4), ER + breast cancer (OR = 0.5252, 95% CI = 0.3589–0.7685, p = 9 × 10 − 4), and heart failure (OR = 1.0026, 95% CI = 1.001–1.0042, p = 0.002). COVID-19 hospitalization was causally linked to heart failure (OR = 1.0017, 95% CI = 1.0006–1.0028, p = 0.002) and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). COVID-19 severity had causal effects on primary biliary cirrhosis (OR = 2.6333, 95% CI = 1.8274–3.7948, p = 2.059 × 10 − 7), celiac disease (OR = 0.0708, 95% CI = 0.0538–0.0932, p = 9.438 × 10–80), and Alzheimer’s disease (OR = 1.5092, 95% CI = 1.1942–1.9072, p = 0.0006). Reverse MR analysis indicated that rheumatoid arthritis, diabetic nephropathy, multiple sclerosis, and total testosterone (female) influence COVID-19 outcomes. We assessed heterogeneity and horizontal pleiotropy to ensure result reliability and employed the Steiger directionality test to confirm the direction of causality.ConclusionsThis study provides a comprehensive analysis of the causal relationships between COVID-19 and diverse health conditions. Our findings highlight the long-term impacts of COVID-19 on human health, emphasizing the need for continuous monitoring and targeted interventions for affected individuals. Future research should explore these relationships to develop comprehensive healthcare strategies.

Efficacy of a cognitive-behavioral digital therapeutic on psychosocial outcomes in rheumatoid arthritis: randomized controlled trial

Cognitive behavioral therapy improves psychosocial outcomes in rheumatoid arthritis (RA), but access is limited. We conducted a randomized controlled trial to evaluate the efficacy of a cognitive-behavioral digital therapeutic, reclarit, on psychosocial outcomes in adult RA patients with impaired health-related quality of life. Participants were randomized to reclarit plus treatment as usual (TAU) or TAU plus educational and informational material (active control). The primary outcome was SF-36 mental (MCS) and physical (PCS) component summary scores at 3 months, with additional assessments at 6 months. reclarit significantly improved SF-36 MCS scores compared to control (mean difference 3.3 [95% CI 0.7, 5.9]; p = 0.014), with high user satisfaction and sustained improvements at 6 months. Depression, anxiety, fatigue, and social/work functioning also improved significantly, while SF-36 PCS, pain, and disability scores did not differ. In conclusion, reclarit offers immediate, effective, evidence-based and personalized psychological support for RA patients.

Red cell distribution width/albumin ratio and mortality risk in rheumatoid arthritis patients: Insights from a NHANES study.

Despite the established negative regulatory effects observed in various diseases like cardiovascular disease and diabetes, the distinct impact of red cell distribution width (RDW) to albumin ratio (RAR) on mortality within the realm of rheumatoid arthritis (RA) remains obscure. This study sought to explore the relationship between RAR and mortality in RA patients. A cohort of 2151 adults with RA from the National Health and Nutrition Examination Survey (NHANES) spanning 2003-2016 was analyzed for RAR levels derived from red cell distribution width and albumin concentrations. Utilizing Cox regression analysis, Kaplan-Meier curves, and Restricted Cubic Spline (RCS) models, we assessed the association between RAR levels and RA mortality while adjusting for potential confounding variables. Participants with higher RAR had a twofold to threefold increased risk of all-cause (HR = 3.10, 95% CI: 2.26-4.24) and cardiovascular mortality (HR = 2.46, 95%CI: 1.26-4.79) versus lower RAR. Kaplan-Meier analysis revealed that the higher RAR group had a significantly lower survival rate compared to the lower RAR group for both all-cause and cardiovascular mortality (both p < .0001), with a more pronounced effect observed for all-cause mortality. Furthermore, the RCS-fitted Cox regression model illustrated a nonlinear positive correlation between RAR levels and RA mortality. Overall, a higher RAR was associated with an increased risk mortality in RA patients. These findings underscore the potential of RAR as a prognostic biomarker in predicting outcomes in RA.

Causal Association of Rheumatoid Arthritis With Adverse Pregnancy Outcomes: Genetic Evidence From Mendelian Randomization.

Although the association of rheumatoid arthritis (RA) to multiple adverse pregnancy outcomes has been well-studied, the association between serum antibody levels in patients with RA and multiple adverse pregnancy outcomes has not been conclusively demonstrated. Here, we comprehensively assessed the causal impact of RA, serologic antibody-positive RA (pRA), and serologic antibody-negative RA (nRA) on the risk of 14 adverse pregnancy outcomes. The causal impact of RA, pRA, and nRA on 14 adverse pregnancy outcomes was comprehensively assessed using two-sample Mendelian randomization (MR). Evidence maps based on the results of these two-sample MR analyses were developed. Data from the UK Biobank and FinnGen databases were utilized for this analysis. The inverse variance weighted (IVW) test was employed as the primary method to estimate causality. "TwoSampleMR" and "MR-PRESSO" packages were used for data analysis in this study. Using two-sample MR analysis, we found a significant positive causal association between RA and increased risk of cesarean section (p=0.003), gestational hypertension (p < 0.001), number of spontaneous miscarriages (p=0.041), preeclampsia (p=0.008), premature rupture of membranes (p=0.030), and preterm (p=0.010). pRA had a significant positive causal association with an increased risk of cesarean section (p=0.012), gestational hypertension (p < 0.001), preeclampsia (p=0.002), and preterm (p=0.007). A significant positive causal association was also established between nRA and gestational hypertension (p=0.010), the number of spontaneous miscarriages (p=0.024), and placental abruption (p=0.027). In addition, we found a causal association between nRA and birth weight (p=0.007), but not between RA and pRA and birth weight. The results of this study have important implications for the individualized treatment of RA patients, especially those with positive serum antibody levels.

Dust Storms Are Associated with an Increase in Outpatient Visits for Rheumatoid Arthritis

Our study is the first to illuminate a previously underexplored dimension in the intricate interplay between environmental factors, specifically dust storms (DSs), and rheumatoid arthritis (RA) outcomes. An Auto Regressive Moving Average (ARMA) time-series estimation model was employed to analyze rheumatoid arthritis outpatient visits, dust storms, air pollution, and meteorology data in Taiwan from 2006 to 2012. The results show that females are three times more likely to experience RA-related issues and seek medical attention. Percentage analysis revealed a 10–15% increase in daily RA outpatient visits on post-event days 1 and 2 compared to non-DS days. However, the time-series estimation indicated a delayed and statistically significant (p &lt; 0.05) increase in RA outpatient visits on post-event day 1 for males but not females. Additionally, a significant increase in RA outpatient visits (p &lt; 0.05) was observed on post-event day 1 among individuals aged 61 and above. Environmental factors such as temperature and SO2 showed strong significance across all genders and age groups (p &lt; 0.001). The findings highlight distinct gender and age disparities regarding the impacts of DS on RA outpatient visits, emphasizing the heightened sensitivity of males to environmental pollutants and the vulnerability of the elderly population.

Summary of Research: Effects of Adalimumab-adbm Versus Adalimumab Reference Product on Patient-Reported Outcomes in Rheumatoid Arthritis: Results from VOLTAIRE-RA.

This Summary of Research overviews the results of a study that looked at patient-reported outcomes in the VOLTAIRE-RA trial (NCT02137226), originally published in Rheumatology and Therapy. A biosimilar is a biologic medicine made to be very similar to the original biologic medicine (also known as the reference product). The VOLTAIRE-RA trial compared the efficacy and safety of an adalimumab biosimilar (Cyltezo®, adalimumab-admb) with the adalimumab reference product, Humira®, in people with rheumatoid arthritis. As part of the VOLTAIRE-RA study, participants took either adalimumab-adbm or adalimumab reference product for 24weeks. Patient-reported outcomes were captured after 12weeks and after 24weeks of treatment to assess the effects of treatment on each participant's health-related quality of life. People with rheumatoid arthritis who were given adalimumab-adbm or adalimumab reference product experienced similar clinically meaningful improvements in their health-related quality of life after 12weeks of treatment. A high proportion of people in this trial who were given adalimumab-adbm or adalimumab reference product reported greater improvement versus a reference US population matched by age and sex. This is notable, as it represents a treatment goal that was difficult to achieve in earlier rheumatoid arthritis trials of non-biologic treatments.

Leveraging the Consolidated Framework for Implementation Research (CFIR) to Develop the American College of Rheumatology's Toolkit for Implementation of Rheumatoid Arthritis Outcome Measures in Clinical Practice: A Qualitative Study.

Despite the recognized benefits of collecting rheumatoid arthritis (RA) outcomes measures, their use in routine care is inconsistent. Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured interviews with United States rheumatologists and practice personnel to assess workflows, opportunities, and challenges in collecting RA outcome measures. Using insights from interviews, we developed the RA Measures Toolkit to enhance their utilization in clinical practice. We invited 138 RISE registry practices and 5 academic medical centers with ≥ 30 patients eligible for RA outcome measures to participate in the study. Practices were classified based on their performance in quality payment programs. Recorded interviews were transcribed verbatim and analyzed thematically using deductive and inductive techniques. The findings were used to create the RA Measures Toolkit. We conducted 20 interviews with 38 participants across 20 practices. Key themes within the CFIR domains highlighted the challenges and best practices in RA outcome measure collection and included: 1) Process: the variability in practices' use of RA outcome measures and the importance of streamlined workflows, 2) Intervention: challenges of integrating PROs into electronic health records (EHRs), and 3) Individual characteristics: importance of clinic culture around quality improvement. Using this data, we developed the RA Toolkit, a multimedia online resource, featuring guidelines, best practices, and educational resources to improve the efficiency of current workflows and to enhance patient care. This study identifies critical gaps in the collection of RA outcome measures in U.S. rheumatology practices and provides actionable recommendations and resources to address challenges via the RA Toolkit.

Barriers to, Facilitators of, and Interventions to Support Treat-to-Target Implementation in Rheumatoid Arthritis: A Systematic Review.

Treat-to-target (T2T) is recommended in the management of rheumatoid arthritis (RA) but its implementation is suboptimal. We aimed to identify interventional strategies targeted at improving T2T implementation in RA by systematically reviewing published evidence on barriers to, facilitators of, and interventions to support T2T implementation. Systematic and scoping literature searches in PubMed/MEDLINE®, BIOSIS Previews®, Derwent Drug File, Embase®, EMCare®, International Pharmaceutical Abstracts, and SciSearch® were conducted to identify barriers/facilitators and interventions relating to T2T implementation in RA. The quality of included studies was assessed using Critical Appraisal Skills Programme (CASP) checklists. Data related to barriers/facilitators and interventions were extracted, grouped, and summarized descriptively, and a narrative synthesis was generated. In total, 146 articles were analyzed, of which 123 (84%) included ≥50% of the items assessed by CASP checklists. Of the 146 studies, 76 evaluated T2T barriers and facilitators, from which 329 relevant statements were identified and regrouped into 18 target areas, including: healthcare professionals' (HCPs') or patients' knowledge or perceptions; patient-HCP communication or alignment; and time or resources. Overall, 56 interventions were identified from 70 studies across the 18 target areas; 54% addressed disease activity or patient-reported outcome assessments. Of the 56 interventions identified, 36 improved T2T implementation and/or patient outcomes in RA. Despite long-established T2T recommendations, there remain many barriers to its implementation. Interventions to improve T2T should be developed further and assessed, with a particular focus on tailoring them to individual countries, regions, and healthcare settings.

Rheumatoid arthritis and adverse pregnancy outcomes: a bidirectional two-sample mendelian randomization study

BackgroundThere is growing evidence of bidirectional associations between rheumatoid arthritis and adverse pregnancy outcomes (APOs) in observational studies, but little is known about the causal direction of these associations. Therefore, we explored the potential causal relationships between rheumatoid arthritis and APOs using a bidirectional two-sample Mendelian randomization (MR) in European and Asian populations.MethodsWe conducted a bidirectional two-sample Mendelian randomization analysis using available summary statistics from released genome-wide association studies. Summary statistics for instrument–outcome associations were retrieved from two separate databases for rheumatoid arthritis and adverse pregnancy outcomes, respectively. The inverse-variance weighted method was used as the primary MR analysis, and cML-MA-BIC was used as the supplementary analysis. MR-Egger, MR pleiotropy residual sum and outlier (MR-PRESSO), and Cochran Q statistic method were implemented as sensitivity analyses approach to ensure the robustness of the results.ResultsOur study showed that a higher risk of rheumatoid arthritis in the European population was associated with gestational hypertension (OR: 1.04, 95%CI: 1.02–1.06), pre-eclampsia (OR: 1.06, 95%CI: 1.01–1.11), fetal growth restriction (OR: 1.08, 95%CI: 1.04–1.12), preterm delivery (OR:1.04, 95%CI: 1.01–1.07). Furthermore, we found no evidence that APOs had causal effects on rheumatoid arthritis in the reverse MR analysis. No association between rheumatoid arthritis and APOs was found in East Asian population. There was no heterogeneity or horizontal pleiotropy.ConclusionsThis MR analysis provides the positive causal association from rheumatoid arthritis to gestational hypertension, pre-eclampsia, fetal growth restriction and preterm delivery genetically. It highlights the importance of more intensive prenatal care and early intervention among pregnant women with rheumatoid arthritis to prevent potential adverse obstetric outcomes.

Using terahertz spectroscopy to quantify bioactive flavonoids in Moxa Wool as predictor of rheumatoid arthritis treatment outcomes

BackgroundMoxibustion, a traditional Chinese medicine practice, employs Moxa Wool, derived from Artemisia argyi. Flavonoids, the key pharmacological constituents in Moxa Wool, are known for their anti-inflammatory and analgesic properties. The purity of Moxa Wool, particularly its flavonoid content, directly influences the efficacy of moxibustion treatments. However, quantifying these bioactive flavonoids accurately and non-destructively has been a challenge. PurposeThis study introduces terahertz spectroscopy as a non-destructive optical detection method for qualitative detection and quantitative analysis of flavonoids in Moxa Wool. By establishing a mathematical model between spectral signals and clinical efficacy, a reliable correlation between flavonoid concentration and the therapeutic effect of moxibustion can be established, providing a potential predictive model for the treatment outcomes of rheumatoid arthritis. Study DesignWe adopted terahertz spectroscopy technology and combined it with terahertz metamaterial biosensors to achieve rapid, efficient, and non-destructive testing of the quality of Moxa Wool. This method reduces the detection time from hours to minutes while lowering the sample detection limit, overcoming the limitations of traditional detection methods in pharmacological research. MethodsThrough terahertz metamaterial biosensors, rapid detection of the purity of Moxa Wool has been achieved. A combination of molecular simulation and terahertz spectroscopy was used to quantitatively analyze the flavonoid content in different purities of Moxa Wool. To ensure accuracy, the quantitative results of flavonoids obtained by terahertz spectroscopy were validated using high-performance liquid chromatography (HPLC). In addition, moxibustion treatment was performed on rats with rheumatoid arthritis using Moxa Wool, and medical indicator information was recorded. A mathematical analysis model was established to evaluate the correlation between flavonoid content and analgesic and anti-inflammatory effects. ResultsTerahertz spectroscopy analysis shows that there is a direct correlation between the flavonoid content in moxibustion and the absorption peak intensity. The maximum R2 in the model analysis is 0.98, indicating a high accuracy in predicting the purity of Moxa Wool. These results were also validated by HPLC. In a rat model, the purity of 30:1 Moxa Wool samples showed a 50 % decrease in TNF-α, IL-1β, and IL-6 levels during treatment compared to low-purity samples, significantly reducing inflammation markers and pain symptoms. Meanwhile, The PLS prediction model established a correlation between terahertz-detected flavonoid levels and treatment outcomes (PWL and IL-1β). The maximum R2 in the model is 0.91, indicating a high correlation between flavonoid levels and the anti-inflammatory and analgesic effects of moxibustion treatment. ConclusionThis study not only demonstrates the effectiveness of terahertz spectroscopy in the pharmacological quantification of bioactive compounds but also establishes a novel predictive model for the efficacy of moxibustion in rheumatoid arthritis treatment. It underscores the potential of integrating traditional medicine insights with advanced technology to enhance therapeutic strategies in pharmacology.

How to develop, validate, and update clinical prediction models using multinomial logistic regression

ObjectivesMulticategory prediction models (MPMs) can be used in health care when the primary outcome of interest has more than two categories. The application of MPMs is scarce, possibly due to added methodological complexities compared to binary outcome models. We provide a guide of how to develop, validate, and update clinical prediction models based on multinomial logistic regression. Study Design and SettingWe present guidance and recommendations based on recent methodological literature, illustrated by a previously developed and validated MPM for treatment outcomes in rheumatoid arthritis. Prediction models using multinomial logistic regression can be developed for nominal outcomes, but also for ordinal outcomes. This article is intended to supplement existing general guidance on prediction model research. ResultsThis guide is split into three parts: 1) outcome definition and variable selection, 2) model development, and 3) model evaluation (including performance assessment, internal and external validation, and model recalibration). We outline how to evaluate and interpret the predictive performance of MPMs. R code is provided. ConclusionWe recommend the application of MPMs in clinical settings where the prediction of a multicategory outcome is of interest. Future methodological research could focus on MPM-specific considerations for variable selection and sample size criteria for external validation.

Can vitamin supplementation improve quality of life and disease severity in patients with rheumatoid arthritis, or is physical activity enough?

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and progressive joint destruction, significantly impacting quality of life. While conventional treatments focus on managing symptoms and slowing disease progression through pharmacological means, the potential role of complementary therapies like vitamin supplementation or increased physical activity has garnered increasing interest. Aim of the Study: This narrative review explores the existing literature on the efficacy and mechanisms of various vitamins in the management of RA. By synthesizing current research findings, we aim to provide a comprehensive overview of how vitamin supplementation might influence RA outcomes, offering insights into potential integrative approaches to enhance patient care. Methods and Materials: A thorough search was conducted using PubMed and Google Scholar, focusing on literature published in the past five years. Vitamins with potential impacts on RA progression were identified and paired with the term "Rheumatoid Arthritis" to collect data on their influence on the disease's incidence and management, as well as the mechanisms involved. Additionally, references from selected articles were reviewed and included in the analysis. This method ensured a comprehensive evaluation of the current evidence regarding vitamin supplementation in RA treatment. Similarly, studies on the impact of physical activity on RA were also reviewed. Results: The influence of physical activity on serum inflammatory markers in RA patients was limited. Vitamin D supplementation significantly reduced disease activity, alleviated pain, and mitigated methotrexate-related side effects, especially in patients with baseline vitamin D deficiency or lower serum levels. In contrast, other vitamins have not exhibited the same positive effects. These findings underscore the need for continued research to optimize the role of various vitamins in managing RA effectively.

The impact of periodontitis and periodontal treatment on rheumatoid arthritis outcomes: an exploratory clinical trial.

Studies suggest rheumatoid arthritis (RA) patients could benefit from periodontal treatment. However, published data are inconsistent, and there is a need for better-controlled research. Our study aims to address these limitations. In this exploratory randomised delayed-start study, 22 RA patients with moderate/severe periodontitis were subjected to full-mouth debridement. Periodontal and rheumatological assessments, including measuring anti-cyclic citrullinated peptide 2 (CCP2) IgG levels, were performed at baseline (V1), 2 months (V2) and 6 months (V3) after step 1 and 2 of periodontal therapy. Primary outcome was changes in disease activity score for 28 joints (DAS28) between V2 and V1. Secondary outcomes were changes in other rheumatological or periodontal clinical parameters (V2 or V3-V1). RA disease activity was significantly higher in RA patients with severe periodontitis compared to moderate periodontitis at baseline, with significant positive correlations between several rheumatological and periodontal parameters. After periodontal treatment, RA patients with severe, but not moderate, periodontitis demonstrated significant improvements in DAS28 (ΔV2-V1, p = 0.042; ΔV3-V1, p = 0.001) and significant reduction in anti-CCP2 IgG levels at V3 (p = 0.032). Periodontal treatment is locally effective in patients with RA and impacts RA disease activity and anti-CCP2 antibody levels in patients with severe periodontitis. Hence, our data suggest that periodontal assessment and treatment should be integrated in the management of RA patients within a treat-to-target strategy. www.isrctn.com, ISRCTN 17950307.

The PTPN22 as Master Regulation in Autoimmune Diseases and Its Susceptibility to Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a long-term autoimmune condition that causes joint inflammation, resulting in pain, tenderness, expansion, and even joint malformation. It mostly causes inflammation and thickening of the synovium, the membrane that lines the joints. Joint erosion, cartilage breakdown, and function loss are all possible outcomes of RA over time. Though it can affect any joint in the body, it usually affects the smaller joints in the hands and feet. A significant role can be played by genetic ability in the progress of rheumatoid arthritis. The review's subject, "PTPN22" (sometimes referred to as "LYP in humans or PEP in mice"), is the typical non receptor PTP belonging to the proline rich subgroup of Type I. PTPN22 is a "major negative regulator of T-cell receptor (TCR) signal transduction" which is mostly express in the immune cells. Interestingly, a mutation in this gene has been related to the onset of many autoimmune disorders. Several genetic variants have been identified that contribute to the risk of developing RA, including rs2476601. This review discussed the PTPN22 as master regulation of immune system and the role of rs2476601 in RA.

Machine Learning Prediction of Treatment Response to Biological Disease-Modifying Antirheumatic Drugs in Rheumatoid Arthritis.

Background: Disease-modifying antirheumatic drugs (bDMARDs) have shown efficacy in treating Rheumatoid Arthritis (RA). Predicting treatment outcomes for RA is crucial as approximately 30% of patients do not respond to bDMARDs and only half achieve a sustained response. This study aims to leverage machine learning to predict both initial response at 6 months and sustained response at 12 months using baseline clinical data. Methods: Baseline clinical data were collected from 154 RA patients treated at the University Hospital in Erlangen, Germany. Five machine learning models were compared: Extreme Gradient Boosting (XGBoost), Adaptive Boosting (AdaBoost), K-nearest neighbors (KNN), Support Vector Machines (SVM), and Random Forest. Nested cross-validation was employed to ensure robustness and avoid overfitting, integrating hyperparameter tuning within its process. Results: XGBoost achieved the highest accuracy for predicting initial response (AUC-ROC of 0.91), while AdaBoost was the most effective for sustained response (AUC-ROC of 0.84). Key predictors included the Disease Activity Score-28 using erythrocyte sedimentation rate (DAS28-ESR), with higher scores at baseline associated with lower response chances at 6 and 12 months. Shapley additive explanations (SHAP) identified the most important baseline features and visualized their directional effects on treatment response and sustained response. Conclusions: These findings can enhance RA treatment plans and support clinical decision-making, ultimately improving patient outcomes by predicting response before starting medication.

Prevalence and Factors Associated with De-escalation of Anti-TNFs in Older Adults with Rheumatoid Arthritis: A Medicare Claims-Based Observational Study.

The aim was to evaluate prevalence and factors associated with anti-tumor necrosis factor (anti-TNF) de-escalation in older adults with rheumatoid arthritis (RA). We identified adults ≥66 years of age with RA on anti-TNF therapy within 6 months after RA diagnosis with at least 6-7 months duration of use (proxy for stable use), using 20% Medicare data from 2008-2017. Patient demographic and clinical characteristics, including concomitant use of glucocorticoid (GC), were collected. Anti-TNF use was categorized as either de-escalation (identified by dosing interval increase, dose reduction, or cessation of use) or continuation. We used (1) an observational cohort design with Cox regression to assess patient characteristics associated with de-escalation and (2) a case-control design with propensity score-adjusted logistic regression to assess the association of de-escalation with different clinical conditions and concomitant medication use. We identified 5106 Medicare beneficiaries with RA on anti-TNF, 65.5% of whom had de-escalation. De-escalation was more likely with older age (hazard ratio [HR] 1.01, 95% confidence interval [CI] 1.01-1.02) or greater comorbidity (HR 1.07, 95% CI 1.05-1.09), but was less likely with low-income subsidy status (HR 0.85, 95% CI 0.78-0.92), adjusting for patient sex and race/ethnicity. Lower odds of de-escalation were associated with serious infection (odds ratio [OR] 0.79, 95% CI 0.66-0.94), new heart failure diagnosis (OR 0.70, 95% CI 0.52-0.95), and long-term GC use (OR 0.84, 95% CI 0.74-0.95), whereas higher odds were associated with concomitant methotrexate use (OR 1.16, 95% CI 1.03-1.31). Anti-TNFs are de-escalated in two-thirds of older adults with RA in usual care. Further study is needed on RA outcomes after anti-TNF de-escalation.

Exploring the mechanism of Sendeng-4 against rheumacid arthritis through integrated serum pharmacochemistry, transcriptomics, and network pharmacology.

Mongolian medicine Sendeng-4 (SD-4) has demonstrated satisfactory clinical treatment outcomes for rheumatoid arthritis (RA); nevertheless, its bioactive components and the related mechanisms have not yet been clearly elucidated. To explore the bioactive chemical components of SD-4 in the treatment of RA and its possible mechanisms, an High Performance Liquid Chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established to simultaneously quantify the main components in SD-4, and ultraperformance LC-Q-Exactive-MS/MS (UPLC-Q-Exactive-MS/MS) was used to identify the phytochemicals absorbed in the serum. Then, using network pharmacology methods, these components were constructed into a compound-target network of RA to predict possible biological targets of SD-4 as well as potential signaling pathways. Transcriptomics analysis and molecular docking were used to validate the results of network pharmacology. Subsequently, we established a complete Freund's adjuvant-induced RA rat model and observed the anti-RA effects of SD-4 through assessments of foot swelling, ankle diameter, arthritis score, morphology, serum inflammatory factors, and histopathological analysis of synovial tissue. Specifically, reverse transcription-quantitative polymerase chain reaction, Western blot, and immunohistochemical analysis were used in animal experiments to validate the pathways of serum phytochemistry, network pharmacology, and transcriptomics. Tannic acid, gallic acid, corilagin, crocin I, gardenoside, ferulic acid, quercetin, limonin, rutin, chlorogenic acid, verbascoside, catechin, epicatechin, myricetin, and dihydromyricetin in SD-4 showed good linearity within their respective concentration ranges (r ≥ 0.9991); the average recovery rate was 93.77%-109.17% (relative standard deviation < 2%). A total of 37 compounds were identified in serum samples. Based on this, network pharmacology methods collected 739 genes related to these identified compounds in SD-4 and 3807 genes related to RA. Network pharmacology and transcriptomic analysis demonstrated that the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway is the most relevant pathway affected by SD-4 in RA. In the experiments, SD-4 treatment reduced ankle swelling and arthritis scores in RA rats, improved symptoms, and reduced the production of inflammatory factors. Compared with the RA model group, SD-4 treatment significantly reduced the expression of PI3K-Akt pathway-related messenger RNA and proteins. In addition, immunohistochemical analysis confirmed these results. This study combined serum phytochemistry, network pharmacology, and transcriptomics to demonstrate that SD-4 can alleviate RA by regulating the PI3K-Akt signaling pathway. This research provides a theoretical basis for the clinical application of SD-4 and offers an effective strategy for the identification of bioactive substances in traditional Chinese medicine formulas and the study of their potential mechanisms.

Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients - identification of novel single nucleotide polymorphism: Cross-sectional study.

The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220-658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS. Three of these polymorphisms were found in the NCBI database's dbSNP (rs2853741, rs2606241, and rs2853742 SNPs), and one SNP polymorphism is novel (657334). The CTAT (657334, rs2853741, rs2606241, and rs2853742 SNPs) haplotype was significantly associated with responder with odd ratio, 95% confidence interval: 0.506, 0.281-0.912 (P value = .022). In contrast, the other haplotypes were not associated with MTX responsiveness. In the multivariate analysis, after adjusting to the effect of age, sex, smoking, and disease duration, the TCrs2853741 genotype was associated with non-responders (P value = .030). In contrast, the ACrs260641 genotype, after adjusting to the effect of age, sex, and smoking, was associated with non-responders (P value = .035). Genetic polymorphism of the TYMS gene, especially in TCrs2853741 and ACrs260641, predicts non-responder to MTX treatment in RA, while the presence of the CTAT haplotype predicts a good response to MTX treatment.

Therapeutic strategies in preclinical stages of rheumatoid arthritis.

Modern therapies and treatment algorithms, such as the treat‑to‑target strategy, have significantly improved outcomes in patients with rheumatoid arthritis (RA) over the past decades. Moreover, the concept of the "window of opportunity" has led to earlier diagnosis and better treatment outcomes. Nevertheless, progressive disease remains a significant clinical issue and socioeconomic burden, which warrants investigation of novel strategies. One of such innovative therapies is primary prevention: treating patients at risk for developing RA for a short period of time to prevent the disease before it occurs. The initiation of treatment in preclinical phases of RA is expected to delay, halt, or even prevent the disease onset or progression in the long term. This review summarizes this new concept, discusses current studies including an overview of therapeutic algorithms and findings, and provides a critical evaluation of pharmacologic approach in the preclinical stages of RA.