Rheumatoid Arthritis Medication Research Articles

Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.

Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. Patients aged ≥ 18years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs[95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. Inthe All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36(0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). The use of bDMARDs was not a time-dependent risk factor for malignancy.

A novel method to monitor rheumatoid arthritis prevalence using hospital and medication databases

BackgroundMost estimates of rheumatoid arthritis (RA) prevalence, including all official figures in Australia and many other countries, are based on self-report. Self-report has been shown to overestimate RA, but the ‘gold standard’ of reviewing individual medical records is costly, time-consuming and impractical for large-scale research and population monitoring. This study provides an algorithm to estimate RA cases using administrative data that can be adjusted for use in multiple contexts to provide the first approximate RA cohort in Australia that does not rely on self-report.MethodsSurvey data on self-reported RA and medications from 25 467 respondents of the Australian Longitudinal Study on Women’s Health (ALSWH) were linked with data from the national medication reimbursement database, hospital and emergency department (ED) episodes, and Medicare Benefits codes. RA prevalence was calculated for self-reported RA, self-reported RA medications, dispensed RA medications, and hospital/ED RA presentations. Linked data were used to exclude individuals with confounding autoimmune conditions.ResultsOf 25 467 survey respondents, 1367 (5·4%) women self-reported disease. Of the 26 840 women with hospital or ED presentations, 292 (1·1%) received ICD-10 codes for RA. There were 1038 (2·8%) cases by the medication database definition, and 294 cases (1·5%) by the self-reported medication definition. After excluding individuals with other rheumatic conditions, prevalence was 3·9% for self-reported RA, 1·9% based on the medication database definition and 0·5% by self-reported medication definition. This confirms the overestimation of RA based on self-reporting.ConclusionsWe provide an algorithm for identifying individuals with RA, which could be used for population studies and monitoring RA in Australia and, with adjustments, internationally. Its balance of accuracy and practicality will be useful for health service planning using relatively easily accessible input data.

Association Between Osteoporosis Self-Assessment Tool for Asians and Airflow Limitation in Japanese Post-Menopausal Women.

This study aimed to reveal the association between the osteoporosis self-assessment tool for Asians (OSTA) and airflow limitation (AL) in post-menopausal Japanese women. This cross-sectional study included 1580 participants undergoing a comprehensive health examination using spirometry and dual-energy X-ray absorptiometry. The OSTA was calculated by subtracting the age in years from the body weight (BW) in kilograms, and the result was multiplied by 0.2. The OSTA risk level was defined as low (>-1), moderate (-4 to -1), or high (<-4). AL was defined as forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.7. The association between the OSTA and AL was assessed using logistic regression analysis. The prevalence of AL was significantly higher in the high OSTA group (15.3%) than in the low OSTA group (3.1%) (p<0.001). In multiple linear regression analysis, the OSTA was independently associated with FEV1/FVC. In logistic regression models adjusted for smoking status, alcohol consumption, current use of medication for diabetes, hyperglycemia, rheumatoid arthritis, second-hand smoke, and ovary removal showed a significantly higher risk of AL (odds ratio: 5.48; 95% confidence interval: 2.90-10.37; p<0.001) in participants with OSTA high risk than in those with OSTA low risk. These results suggest that the OSTA high risk indicates reduced BMD at the femoral neck and presence of AL in Japanese post-menopausal women aged ≥45 years.

Fatty acid-arginine vesicles with prominent encapsulation efficiency and substantial transdermal delivery of sinomenine hydrochloride

In clinical practice, sinomenine hydrochloride (SH) is a valuable and promising medication for rheumatoid arthritis. However, oral administration of SH is less bioavailable with adverse reactions to the digestive system, blood circulation, and nervous system, among which rash, gastric ulcer, gastric haemorrhage and anaphylactic shock are the most common. Owing to a short half-life in the human body (0.791 h), patient compliance is greatly reduced, resulting in frequent administration for patient treatment. Therefore, SH encapsulated in vesicles with amphiphilic layers would be more stable and have fewer side effects. In this study, a transdermal drug delivery system (TDDS) for SH was designed utilizing fatty acid vesicles as carriers. The physicochemical properties and aggregate morphology of two carriers: arginine-oleic acid ([Arg][Ole]) and arginine-decanoic acid ([Arg][Dec]) were investigated, and the SH encapsulation method by the above materials was optimized and verified by single factor and central composite design (CCD) response surface methods. Notably, the encapsulation efficiency (EE) of SH in [Arg][Dec] vesicles was increased to 83.5 % and the centrifugal stability (CS) to 90.4 %. Moreover, as a result of the Conductor-like screening model for real solvents (COSMO-RS) calculation, it was found that the interaction between [Arg][Dec] and SH was stronger than that of [Arg][Ole], aligning with experimental results. In comparison to the sustained release period in water, the in vitro release experiment showed that the [Arg][Ole] and [Arg][Dec] vesicles could be prolonged to 17 hours. Importantly, the cumulative skin permeability of [Arg][Dec] vesicles reached 1665.59 μg·cm−2 after 48 h, which is much higher than the previous literature value of around 663 μg·cm−2. These results suggest that vesicles provide a viable method for transdermal delivery of SH.

Adjunct role of potassium-rich vegetarian diet and a novel potassium food supplement to improve pain in chronic rheumatoid arthritis on supervised standard care: a randomised controlled study

IntroductionAn earlier food survey showed dietary potassium deficiency in rheumatoid arthritis (RA).ObjectiveTo evaluate an adjunct role of oral potassium to reduce joint pain in RA.Methods172 consenting eligible symptomatic patients (median...

Patient trust, quality communication, and medication adherence in rheumatoid arthritis patients highly affected by social determinants of health.

Because medication adherence is essential to the management of rheumatoid arthritis (RA), identifying (1) subgroups at high risk for low medication adherence and (2) modifiable factors potentially contributing to low adherence can impact patient outcomes. This study aims to describe the relationships between anxiety, trust in the provider, quality patient-provider communication, fatigue, RA knowledge, adverse medication effects, disease activity, RA medications, disease duration, patient satisfaction, and medication intolerance and cluster factors to differentiate RA-patient subgroups. This observational study used correlation analysis, linear regression, and cluster analysis with determination decisions based on Schwarz's Bayesian Criterion. Medication adherence was higher in non-Hispanic, White participants, inversely correlated with disease activity and pain intensity, and positively correlated with trust in the provider. Patient satisfaction was higher among those with a shorter time since diagnosis, and was negatively associated with disease activity, pain intensity and interference, fatigue, and anxiety. It was positively associated with RA knowledge, trust in provider and quality of patient-provider communication. Medication intolerance differed by disease duration and was positively correlated with disease activity, pain interference, and fatigue. Of the two clusters, Cluster 1 participants had greater medication adherence and patient satisfaction, and lower medication intolerance. They were of higher income, employed, and non-Hispanic, White persons with a shorter disease duration and lower perceived pain intensity/interference, fatigue, and anxiety. They were more knowledgeable about RA with higher trust in their provider and perceived quality of patient-provider communication. A low medication adherence RA-patient subgroup-highly affected by social determinants of health and with unique relational and clinical characteristics was identified.

Diminished antibody response to SARS-CoV-2 in rheumatoid arthritis compared to metabolic disorders following the primary series of vaccinations and its recovery with a booster: A single-center prospective observational study.

To compare antibody responses after vaccinations between patients with rheumatoid arthritis (RA) and patients with metabolic disorders (MD). The study places special emphasis on understanding how common diseases affect antibody responses in individuals with RA within real-world settings. The participants were 117 patients with RA (66 with RA only and 51 with RA and MD) and 37 patients with MD who received both the primary series of vaccinations and a booster. Antibody titers were compared after the primary series of vaccinations and a booster, and factors influencing the antibody response were assessed. Following the primary series of vaccinations, a significant reduction in antibody titers was observed in patients with longer days between vaccination and antibody measurement, the use of IL-6 inhibitors, selective T cell co-stimulation modulators, and methotrexate. Comorbid MD did not exhibit significant influences on antibody response in RA. Notably, the presence of RA itself was not significant in multivariate linear regression analysis. After the administration of the booster, however, day between vaccination and antibody measurement, the use of IL-6 inhibitor, and methotrexate no longer remained significant. Only the use of selective T cell co-stimulation modulators retained its significance. MD did not exhibit a significant impact on antibody responses in RA patients. The reduced antibody response following the primary series in RA patients appeared to be attributed more to specific RA medications rather than to the disease itself. Booster vaccines are vital in restoring the antibody response in RA.

Using the technology acceptance model to assess clinician perceptions and experiences with a rheumatoid arthritis outcomes dashboard: qualitative study

BackgroundImproving shared decision-making using a treat-to-target approach, including the use of clinical outcome measures, is important to providing high quality care for rheumatoid arthritis (RA). We developed an Electronic Health Record (EHR) integrated, patient-facing sidecar dashboard application that displays RA outcomes, medications, and lab results for use during clinical visits (“RA PRO dashboard”). The purpose of this study was to assess clinician perceptions and experiences using the dashboard in a university rheumatology clinic.MethodsWe conducted focus group (FG) discussions with clinicians who had access to the dashboard as part of a randomized, stepped-wedge pragmatic trial. FGs explored clinician perceptions towards the usability, acceptability, and usefulness of the dashboard. FG data were analyzed thematically using deductive and inductive techniques; generated themes were categorized into the domains of the Technology Acceptance Model (TAM).Results3 FG discussions were conducted with a total of 13 clinicians. Overall, clinicians were enthusiastic about the dashboard and expressed the usefulness of visualizing RA outcome trajectories in a graphical format for motivating patients, enhancing patient understanding of their RA outcomes, and improving communication about medications. Major themes that emerged from the FG analysis as barriers to using the dashboard included inconsistent collection of RA outcomes leading to sparse data in the dashboard and concerns about explaining RA outcomes, especially to patients with fibromyalgia. Other challenges included time constraints and technical difficulties refreshing the dashboard to display real-time data. Methods for integrating the dashboard into the visit varied: some clinicians used the dashboard at the beginning of the visit as they documented RA outcomes; others used it at the end to justify changes to therapy; and a few shared it only with stable patients.ConclusionsThe study provides valuable insights into clinicians’ perceptions and experiences with the RA PRO dashboard. The dashboard showed promise in enhancing patient-clinician communication, shared decision-making, and overall acceptance among clinicians. Addressing challenges related to data collection, education, and tailoring dashboard use to specific patient populations will be crucial for maximizing its potential impact on RA care. Further research and ongoing improvements in dashboard design and implementation are warranted to ensure its successful integration into routine clinical practice.

Evaluating Factors Associated With Telehealth Appropriateness in Outpatient Rheumatoid Arthritis Encounters Using the Encounter Appropriateness Score for You (EASY).

Telehealth has been proposed as a safe and effective alternative to in-person care for rheumatoid arthritis (RA). The purpose of this study was to evaluate factors associated with telehealth appropriateness in outpatient RA encounters. A prospective cohort study (January 1, 2021, to August 31, 2021) was conducted using electronic health record data from outpatient RA encounters in a single academic rheumatology practice. Rheumatology providers rated the telehealth appropriateness of their own encounters using the Encounter Appropriateness Score for You (EASY) immediately following each encounter. Robust Poisson regression with generalized estimating equations modeling was used to evaluate the association of telehealth appropriateness with patient demographics, RA clinical characteristics, comorbid noninflammatory causes of joint pain, previous and current encounter characteristics, and provider characteristics. During the study period, 1823 outpatient encounters with 1177 unique patients with RA received an EASY score from 25 rheumatology providers. In the final multivariate model, factors associated with increased telehealth appropriateness included higher average provider preference for telehealth in prior encounters (relative risk [RR] 1.26, 95% CI 1.21-1.31), telehealth as the current encounter modality (RR 2.27, 95% CI 1.95-2.64), and increased patient age (RR 1.05, 95% CI 1.01-1.09). Factors associated with decreased telehealth appropriateness included moderate (RR 0.81, 95% CI 0.68-0.96) and high (RR 0.57, 95% CI 0.46-0.70) RA disease activity and if the previous encounters were conducted by telehealth (RR 0.83, 95% CI 0.73-0.95). In this study, telehealth appropriateness was most associated with provider preference, the current and previous encounter modality, and RA disease activity. Other factors like patient demographics, RA medications, and comorbid noninflammatory causes of joint pain were not associated with telehealth appropriateness.

Developing and externally validating multinomial prediction models for methotrexate treatment outcomes in patients with rheumatoid arthritis: results from an international collaboration

ObjectivesIn rheumatology, there is a clinical need to identify patients at high risk (>50%) of not responding to the first-line therapy methotrexate (MTX) due to lack of disease control or discontinuation due to adverse events (AEs). Despite this need, previous prediction models in this context are at high risk of bias and ignore AEs. Our objectives were to (i) develop a multinomial model for outcomes of low disease activity and discontinuing due to AEs 6 months after starting MTX, (ii) update prognosis 3-month following treatment initiation, and (iii) externally validate these models. Study Design and SettingA multinomial model for low disease activity (submodel 1) and discontinuing due to AEs (submodel 2) was developed using data from the UK Rheumatoid Arthritis Medication Study, updated using landmarking analysis, internally validated using bootstrapping, and externally validated in the Norwegian Disease-Modifying Antirheumatic Drug register. Performance was assessed using calibration (calibration-slope and calibration-in-the-large), and discrimination (concordance-statistic and polytomous discriminatory index). ResultsThe internally validated model showed good calibration in the development setting with a calibration-slope of 1.01 (0.87, 1.14) (submodel 1) and 0.83 (0.30, 1.34) (submodel 2), and moderate discrimination with a c-statistic of 0.72 (0.69, 0.74) and 0.53 (0.48, 0.59), respectively. Predictive performance decreased after external validation (calibration-slope 0.78 (0.64, 0.93) (submodel 1) and 0.86 (0.34, 1.38) (submodel 2)), which may be due to differences in disease-specific characteristics and outcome prevalence. ConclusionWe addressed previously identified methodological limitations of prediction models for outcomes of MTX therapy. The multinomial approach predicted outcomes of disease activity more accurately than AEs, which should be addressed in future work to aid implementation into clinical practice.

Rheumatoid arthritis and cardiovascular comorbidities

Rheumatoid arthritis (RA) is the most common rheumatologic disease characterized by inflammation with a definite relationship with heart disease. Impaired immunity, chronic inflammation, genetic susceptibility, autonomic nervous system (ANS) dysfunction, altered metabolic profile have been blamed for ischemic and non-ischemic heart diseases in RA patients. Medications used in RA treatment can also modify the risk of heart diseases by different mechanisms. Understanding the pathogenesis is essential to prevent early cardiac dysfunction in RA patients. Fundamental cellular and molecular mechanisms of pathogenesis await further elucidation. Disease management is of great importance since the cardiovascular (CV) events are known to be reduced with low disease activity. Discovery of new mechanisms will pave the way for the development of novel treatment modalities. This review highlights the epidemiology, pathogenesis, risk factors, diagnosis and screening methods and management of CV comorbidities in RA patients. Besides impact of RA medications and exercise on CV risk are summarized.

The RESIST Study: Do TNF Inhibitors Protect Against Cognitive Decline in Rheumatoid Arthritis Patients With Mild Cognitive Impairment?

AbstractBackgroundRheumatoid arthritis (RA) is an autoimmune disease characterised by chronic inflammation in the joint synovium. Considering growing research interest into the role that systemic inflammation might play in the pathogenesis of Alzheimer’s disease (AD), studying cognitive decline in RA patients can provide important insights into the potential effects of inflammation on cognitive health. Furthermore, evidence suggests that biological drugs used to treat RA, specifically TNF inhibitors (TNFi), may protect against AD progression by reducing systemic inflammation. The rheumatoid arthritis medication and memory study (RESIST) is a multicentre longitudinal observational study which aims to compare rates of cognitive decline in adults with both RA and mild cognitive impairment who are on either a conventional synthetic disease modifying anti‐rheumatic drug (csDMARD) or a TNFi.Method251 participants were recruited (160 on csDMARDs, 91 on TNFis). Participants completed assessments at six‐month intervals for eighteen months. The primary outcome was performance on the Free and Cued Selective Reminding Test (FCSRT). It was hypothesised that the rate of decline in FCSRT score would be lower among participants taking TNFis.ResultBetween‐groups ANCOVA was conducted to compare mean FCSRT scores at 12/18 months, adjusting for baseline score, age, disease activity, pain, wellbeing, depressive symptoms and physical function. Results showed that neither group declined in FCSRT free recall score on average over the 18 month follow‐up period, and that there was no significant difference between groups at 12 (mean difference = 0.59, 95% CI = ‐1.54, 2.72) or 18 months (mean difference = 1.24, 95% CI = ‐0.99, 3.47).ConclusionThe absence of decline in FCSRT performance in either group was unexpected. These findings raise the possibility that both csDMARDs and TNFis may protect against cognitive decline However, a major limitation of the study was attrition due to the COVID‐19 pandemic, which may have influenced results – those who experienced a greater degree of cognitive decline may have been more likely to withdraw from the study. Additional planned analyses will examine the potential moderating effect of APOE genotype, and the relationship between peripheral serum C reactive protein, cytokine levels and cognitive outcomes.

A Web-Based Patient Empowerment to Medication Adherence Program for Patients With Rheumatoid Arthritis: Feasibility Randomized Controlled Trial.

Living with a chronic illness such as rheumatoid arthritis (RA) requires medications and therapies, as well as long-term follow-up with multidisciplinary clinical teams. Patient involvement in the shared decision-making process on medication regimens is an important element in promoting medication adherence. Literature review and needs assessment showed the viability of technology-based interventions to equip patients with knowledge about chronic illness and competencies to improve their adherence to medications. Thus, a web-based intervention was developed to empower patients living with RA to adhere to their disease-modifying antirheumatic drugs (DMARDs) medication regimen. This study aims to discuss the intervention mapping process in the design of a web-based intervention that supports patient empowerment to medication adherence and to evaluate its feasibility among patients living with RA. The theory-based Patient Empowerment to Medication Adherence Programme (PE2MAP) for patients with RA was built upon the Zimmerman Psychological Empowerment framework, a web-based program launched through the Udemy website. PE2MAP was developed using a 6-step intervention mapping process: (1) needs assessment, (2) program objectives, (3) conceptual framework to guide the intervention, (4) program plan, (5) adoption, and (6) evaluation involving multidisciplinary health care professionals (HCPs) and a multimedia team. PE2MAP is designed as a 4-week web-based intervention program with a complementary RA handbook. A feasibility randomized controlled trial was completed on 30 participants from the intervention group who are actively taking DMARD medication for RA to test the acceptability and feasibility of the PE2MAP. The mean age and disease duration of the 30 participants were 52.63 and 8.50 years, respectively. The feasibility data showed 87% (n=26) completed the 4-week web-based PE2MAP intervention, 57% (n=17) completed all 100% of the contents, and 27% (n=8) completed 96% to 74% of the contents, indicating the overall feasibility of the intervention. As a whole, 96% (n=24) of the participants found the information on managing the side effects of medications, keeping fit, managing flare-ups, and monitoring joint swelling/pain/stiffness as the most useful contents of the intervention. In addition, 88% (n=23) and 92% (n=24) agreed that the intervention improved their adherence to medications and management of their side effects, including confidence in communicating with their health care team, respectively. The dos and do nots of traditional Chinese medicine were found by 96% (n=25) to be useful. Goal setting was rated as the least useful skill by 6 (23.1%) of the participants. The web-based PE2MAP intervention was found to be acceptable, feasible, and effective as a web-based tool to empower patients with RA to manage and adhere to their DMARD medications. Further well-designed randomized controlled trials are warranted to explore the effectiveness of this intervention in the management of patients with RA.

Definition of rheumatoid arthritis flare based on SDAI and CDAI

ObjectiveTo develop and validate definitions for disease flares in rheumatoid arthritis (RA) based on the quantitative Simplified and Clinical Disease Activity Indices (SDAI, CDAI).MethodsWe analysed RA treatment courses from the...

A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort.

This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper. A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper. The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and twoin the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P<0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213). In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

The Effect of Selegiline on Reducing Oxidative Stress in Polymorphonuclear Blood Cells (Lymphocytes) Isolated from Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a persistent condition resulting in an inflammatory response abide by the pathological mechanism of autoimmunity that causes the cartilage, bone, and joint tissues to deteriorate, lowering one’s quality of life in general. Several studies have suggested a significant association between oxidative stress caused by leukocyte-mediated inflammatory responses and the conversion of a substantial amount of oxygen into diverse free radicals, resulting in oxidative harm, including the chronic nature of rheumatoid arthritis. The utilization of DMARDs which are known as biologic and conventional disease-modifying antirheumatic drugs, has exhibited encouraging results. However, it is crucial to prioritize the discovery of novel and efficacious medications for rheumatoid arthritis in order to address the constraints associated with current therapeutic approaches. Selegiline, a synthetic drug primarily employed to manage Parkinson’s disease, predominantly interferes with the MAO-B enzyme, also known as monoamine oxidase. Additionally, it has been demonstrated to possess free radical-neutralizing properties. The goal of this study is to assess the effectiveness of selegiline in reducing oxidative stress indicators in peripheral blood mononuclear lymphocyte cells isolated from individuals diagnosed with RA. Peripheral blood was collected from 20 RA patients in accordance with the American College of Rheumatology standard. Lymphocytes were isolated following incubation with 1.5 μg/mL phorbol myristate acetate (PMA) and treatment with different concentrations (50–200 μg/mL) of selegiline. This study reveals that selegiline in concentrations of 150 and 200 μg/mL was effective enough to alleviate oxidative stress by scavenging free radicals and improving the level of natural defensive enzymes playing as antioxidants. Therefore, it can be concluded that the MAO-B inhibitor selegiline has potential as a non-toxic repurposed medicine for curtailing the pathological effects of oxidative overload during RA, unlocking the opportunity for further investigation into the impact on other inflammatory cells, such as neutrophils.

Solvent role in electronic energies, experimental vibrational studies, surface and biological analysis of Ethyl Gallate: In-vitro cytotoxicity assay

Ethyl Gallate is a phytochemical molecule found in the seeds of maprange mangoes that has significant biological effects, including anti-autoimmune behavior. Experimental and theoretical analysis of Ethyl Gallate was carried out to understand the structural and biological activity of the compound. A stable molecular structure of Ethyl Gallate was found, and the geometrical variables were depicted using density functional theory (DFT), a popular approach for electronic structure computation. The structure is spectroscopically characterized using FT-IR and FT-RAMAN methods. Various solvents were utilized to record the UV–visible spectra of Ethyl Gallate, and electronic characteristics, including HOMO-LUMO energies, were measured. Software packages Multiwfn 3.7 and Multiwfn 3.8 are used to provide a thorough topological study of Ethyl Gallate. Natural bond orbital study was also performed. Molecular docking research shows that the inhibitory nature of Ethyl Gallate with 2axj protein functions as an anti-immune agent for Rheumatoid arthritis medication discovery. Additionally, Cell growth and survival were assessed using the MTT assay. By MTT assay, the IC50 value of Ethyl Gallate was 275 μg. Anti-inflammatory activity was obtained as well.

Schisandrin treatment suppresses the proliferation, migration, invasion, and inflammatory responses of fibroblast-like synoviocytes from rheumatoid arthritis patients and attenuates synovial inflammation and joint destruction in CIA mice.

Rheumatoid arthritis (RA) is a systemic autoimmune disease causing joint dysfunction. As disease-modifying anti-rheumatic drugs (DMARDs) have poor efficacy in 20% to 25% of RA patients, additional novel RA medications are urgently needed. Schisandrin (SCH) has multiple therapeutic effects. However, whether SCH is effective against RA remains unknown. To investigate how SCH affects the abnormal behaviours of RA fibroblast-like synoviocytes (FLSs) and further elucidate the underlying mechanism of SCH in RA FLSs and collagen-induced arthritis (CIA) mice. Cell Counting Kit-8 (CCK8) assays were used to characterize cell viability. EdU assays were performed to assess cell proliferation. Annexin V-APC/PI assays were used to determine apoptosis. Transwell chamber assays were used to measure cell migration and invasion in vitro. RT-qPCR was used to assess proinflammatory cytokine and MMP mRNA expression. Western blotting was used to detect protein expression. RNA sequencing was performed to explore the potential downstream targets of SCH. CIA model mice were used to assess the treatment efficacy of SCH in vivo. Treatments with SCH (50, 100, and 200 μΜ) inhibited RA FLSs proliferation, migration, invasion, and TNF-α-induced IL-6, IL-8, and CCL2 expression in a dose-dependent manner but did not affect RA FLSs viability or apoptosis. RNA sequencing and Reactome enrichment analysis indicated that SREBF1 might be the downstream target in SCH treatment. Furthermore, knockdown of SREBF1 exerted effects similar to those of SCH in inhibiting RA FLSs proliferation, migration, invasion, and TNF-α-induced expression of IL-6, IL-8, and CCL2. Both SCH treatment and SREBF1 knockdown decreased activation of the PI3K/AKT and NF-κB signalling pathways. Moreover, SCH ameliorated joint inflammation and cartilage and bone destruction in CIA model mice. SCH controls the pathogenic behaviours of RA FLSs by targeting SREBF1-mediated activation of the PI3K/AKT and NF-κB signalling pathways. Our data suggest that SCH inhibits FLS-mediated synovial inflammation and joint damage and that SCH might have therapeutic potential for RA.

Patient Perceptions of Rheumatoid Arthritis Blood Work: A Cross-Sectional Survey in the ArthritisPower Registry.

To examine how patients with rheumatoid arthritis (RA) perceive RA-related laboratory testing and the potential utility of a blood test to predict treatment response to a new RA medication. ArthritisPower members with RA were invited to participate in a cross-sectional survey on reasons for laboratory testing plus a choice-based conjoint analysis exercise to determine how patients value different attributes of a biomarker-based test to predict treatment response. Most patients perceived that their doctors ordered laboratory tests to check for active inflammation (85.9%) or assess medication side effects (81.2%). The most commonly ordered blood tests used to monitor RA were complete blood counts, liver function tests, and those measuring C-reactive protein (CRP) and erythrocyte sedimentation rate. Patients felt CRP was most helpful in understanding their disease activity. Most worried their current RA medication would eventually stop working (91.4%) and they would waste time trying a new RA medication that may not work for them (81.7%). For patients who would require a future change in RA treatment, a majority (89.2%) reported that they would be very/extremely interested in a blood test that could help predict whether such new medication would be effective. Highly accurate test results (improving the chance RA medication will work from 50% to 85-95%) were more important to patients than low out-of-pocket cost (<$20) or minimal wait time (<7 days). Patients consider RA-related blood work important for monitoring of inflammation and medication side effects. They worry about treatment effectiveness and would undergo testing to accurately predict treatment response.

Does the Type of Failure and the Choice of the Second Biologic Influence Response and Persistence on Medication in Rheumatoid Arthritis?

The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily. Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch. Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent. Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic.