Rheumatoid Arthritis Medication Research Articles

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.

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.

Moxibustion combined with western medication for rheumatoid arthritis with blood stasis obstruction and its effect on platelet activation

To investigate the clinical efficacy and action mechanism of moxibustion combined with western medication for rheumatoid arthritis (RA) with blood stasis obstruction. Fifty-six patients of RA with blood stasis obstruction were randomly divided into an observation group and a control group, with 28 patients in each group. The patients in the control group were treated with oral administration of leflunomide tablets and celecoxib capsules, while the patients in the observation group were treated with moxibustion in addition to the treatment used in the control group. Moxibustion was performed at bilateral Zusanli (ST 36), Shenshu (BL 23), Xuehai (SP 10), and ashi points, once every other day, three times a week. The treatment duration for both groups was 12 weeks. The TCM syndrome score, disease activity score-28 (DAS-28), rheumatoid factor (RF), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), hemorheological indexes (whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity), serum calcium ion (Ca2+) level, and platelet count (PLT) were observed before and after treatment, and the clinical efficacy was evaluated after treatment in the two groups. Compared with those before treatment, the TCM syndrome scores, DAS-28 scores, RF, hs-CRP, ESR, whole blood viscosity high shear, whole blood viscosity low shear, plasma viscosity, and PLT were decreased after treatment in both groups (P<0.01), with the observation group showing lower values compared with those in the control group (P<0.05). Compared with those before treatment, the serum Ca2+ levels were increased after treatment in both groups (P<0.01), and the observation group showed a higher increase than that in the control group (P<0.05). The total effective rate was 85.7% (24/28) in the observation group, which was higher than 67.9% (19/28) in the control group (P<0.05). Moxibustion combined with western medication could alleviate clinical symptoms in patients with RA of blood stasis obstruction, and its mechanism may be related to the inhibition of platelet activation.

Identification of Cell-Specific Differential DNA Methylation Associated With Methotrexate Treatment Response in Rheumatoid Arthritis.

We undertook this study to estimate changes in cell-specific DNA methylation (DNAm) associated with methotrexate (MTX) response using whole blood samples collected from rheumatoid arthritis (RA) patients before and after initiation of MTX treatment. Patients included in this study were from the Rheumatoid Arthritis Medication Study (n=66) and the University of California San Francisco Rheumatoid Arthritis study (n=11). All patients met the American College of Rheumatology RA classification criteria. Blood samples were collected at baseline and following treatment. Disease Activity Scores in 28 joints using the C-reactive protein level were collected at baseline and after 3-6 months of treatment with MTX. Methylation profiles were generated using the Illumina Infinium HumanMethylation450 and MethylationEPIC v1.0 BeadChip arrays using DNA from whole blood. MTX response was defined using the EULAR response criteria (responders showed good/moderate response; nonresponders showed no response). Differentially methylated positions were identified using the Limma software package and Tensor Composition Analysis, which is a method for identifying cell-specific differential DNAm at the CpG level from tissue-level ("bulk") data. Differentially methylated regions were identified using Comb-p software. We found evidence of differential global methylation between treatment response groups. Further, we found patterns of cell-specific differential global methylation associated with MTX response. After correction for multiple testing, 1 differentially methylated position was associated with differential DNAm between responders and nonresponders at baseline in CD4+ T cells, CD8+ T cells, and natural killer cells. Thirty-nine cell-specific differentially methylated regions associated with MTX treatment response were identified. There were no significant findings in analyses of whole blood samples. We identified cell-specific changes in DNAm that were associated with MTX treatment response in RA patients. Future studies of DNAm and MTX treatment response should include measurements of DNAm from sorted cells.

P046 A multinomial approach to prediction of methotrexate treatment response and discontinuation due to adverse events in rheumatoid arthritis

Abstract Background/Aims As recommended by the NICE guidelines, methotrexate (MTX) is typically prescribed as the first line therapy for patients with rheumatoid arthritis (RA). However, around 40% of patients do not respond to MTX at 6 months and around 80% experience adverse events (AEs). Our previous systematic review identified that clinical prediction models of MTX outcomes suffered from methodological limitations, including a lack of validation, suboptimal handling of missing data, and no consideration of competing risks, such as patients discontinuing due to adverse events (AEs). These shortcomings resulted in high risk of bias and should be addressed to aid the implementation of outcome prediction in clinical practice. Therefore, this study aimed to (i) develop a multinomial prediction model for estimating an individual’s risks of not achieving low disease activity (LDA) and discontinuing due to AEs at 6 months after starting MTX, using information observable at the starting point of treatment, (ii) update prognosis at 3 months, and (iii) internally validate these models to assess performance. Methods Data came from the national multi-centre (n = 38) Rheumatoid Arthritis Medication Study (RAMS), which recruited patients with a diagnosis of RA or undifferentiated polyarthritis starting MTX for the first time. We conducted a Patient and Public Involvement focus group with past and current MTX users, which informed our outcome choice of LDA (DAS28 ≤3.2). A multinomial logistic regression (MLR) was used to develop a prediction model that estimated the probabilities of three outcomes: 1) not in LDA, 2) achieved LDA, and 3) discontinued due to AEs. The updated model at 3 months was conditional on patients not having achieved LDA. Missing data was handled using multiple imputation and models were internally validated through bootstrapping. Calibration, discrimination, and variance explained was assessed to quantify model performance. Results A total of 1632 patients were included in the analysis. At 6 months, 756 (46%) patients achieved LDA, 730 (45%) were not in LDA, and 146 (9%) discontinued due to AEs. The updated model at 3 months included 1179 (72%) patients as they had not achieved LDA. For the LDA outcome pair, the c-statistic was 0.73 (0.70, 0.75), while it was 0.54 (0.49, 0.59) for the AEs outcome. The calibration slope was 0.99 (0.85, 1.12) and 0.74 (0.23, 1.23), respectively. Predictive performance at 3 months was similar to baseline. Conclusion Our MLR models handled outcomes of disease activity and AEs simultaneously. We were able to predict outcomes of LDA more accurately than AEs and performance was better in terms of calibration, which is crucial for the clinical utility of a prediction model. This modelling approach could provide more clinically useful and realistic predictions of MTX outcomes, as competing risks such as AEs have previously been ignored. Disclosure C.K. Gehringer: None. G.P. Martin: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; BMS and Pfizer. S.M.M. Verstappen: None. J.C. Sergeant: None.

Nanomedicine is more than a supporting role in rheumatoid arthritis therapy.

Rheumatoid arthritis(RA) is an autoimmune disorder that affects the joints. Various medications successfully alleviate the symptoms of RA in clinical. Still, few therapy strategies can cure RA, especially when joint destruction begins, and there is currently no effective bone-protective treatment to reverse the articular damage. Furthermore, the RA medications now used in clinical practice accompany various adverse side effects. Nanotechnology can improve the pharmacokinetics of traditional anti-RA drugs and therapeutic precision through targeting modification. Although the clinical application of nanomedicines for RA is in its infancy, preclinical research is rising. Current anti-RA nano-drug studies mainly focus on the following: drug delivery systems, nanomedicines with anti-inflammatory and anti-arthritic properties, biomimetic design with better biocompatibility and therapeutic features, and nanoparticle-dominated energy conversion therapies. These therapies have shown promising therapeutic benefits in animal models, indicating that nanomedicines are a potential solution to the current bottleneck in RA treatment. This review will summarize the present state of anti-RA nano-drug research.

677 Do Flare-Ups in Systemic Disease Activity Correlate to Cervical Deformity in Patients With Rheumatoid Arthritis?

INTRODUCTION: Following the introduction of biological DMARDs in Rheumatoid Arthritis (RA) treatment, cervical spine deformity seems to be less prevalent in those patients. It seems that this vast decline in patients with Atlanto-axial Subluxation (AAS), Subaxial Subluxation (SAS) or Vertical Subluxation (VS) is correlated to better control of systemic disease activity (DAS). The aim of the current study is to correlate the frequency of flare-ups in DAS to cervical spine deformity. METHODS: 272 RA patients were included and cervical deformity (AAS and/or SAS) was observed in 108 patients. 84 (31%) patients were in remission at 10 years FU and 206 (75%) of patients reached remission at least once during 10 years FU. Patients with cervical spine deformity at 10 years had less flare-ups (1.26) in DAS than patients without cervical spine deformity (1.58; 95% CI: 0.013-0.627). RESULTS: So, even though the BeSt Trial was designed to optimize treatment, 40% of the patients still developed RA-associated cervical spine deformity. However, remarkably, patients with more flares had less cervical deformity. This may be explained by the treatment regimen that anti-inflammatory medication is augmented upon measuring a systemic flare-up. CONCLUSIONS: This raises the hypothesis that RA medication treatment regimes should not be solely aimed at DAS values, as they are currently defined, in order to avoid cervical deformity in RA in the long term.

Rheumatoid arthritis patients are at increased risk for adverse events following lumbar discectomy

BACKGROUND CONTEXTLumbar discectomy is a common procedure for which patients with rheumatoid arthritis (RA) may be considered. RA is an autoinflammatory disease that may predispose patients to postoperative adverse outcomes. PURPOSETo assess the relative odds of adverse events after lumbar discectomy for those with versus without RA in a large, national, administrative dataset. STUDY DESIGN/SETTINGRetrospective cohort study using the 2010 to 2020 MSpine PearlDiver dataset. PATIENT SAMPLEAfter exclusion of patients under 18 years old, those with any trauma, neoplasm, or infection diagnosis within the month before lumbar discectomy, and any patients who had any alternative lumbar spinal surgery performed on the same day as lumbar discectomy, we identified 36,479 lumbar discectomy patients. 2,937 (8.1%) of these patients had a prior diagnosis of RA. After matching 4:1 by patient age, sex, and Elixhauser Comorbidity Index (ECI, a longitudinal measure of patient comorbidity burden generated via ICD-9 and 10 diagnosis codes), 8,485 lumbar discectomy patients without RA and 2,149 with RA were included. OUTCOME MEASURESIncidence of severe and minor adverse events in the 90-days following lumbar discectomy, predictive factors for adverse events within 90-days of lumbar discectomy, risk of adverse events within 90-days of lumbar discectomy stratified by patient medication regimen, 5-year survival to reoperation following lumbar discectomy. METHODSPatients undergoing lumbar discectomy were identified from the PearlDiver MSpine dataset. The subset of those with versus without RA were identified and matched 1:4 based on patient age, sex, and ECI scores. The incidence of 90-day adverse events in the two groups was determined and compared by univariate and multivariate analyses. Subgroup analysis was performed based on RA medications being taken. RESULTSMatched lumbar discectomy patients with RA (n=2,149) and without RA (n=8,485) were identified. Controlling for patient age, sex, and ECI, those with RA were at significantly higher odds of any (odds ratio [OR] 3.30), severe (OR 2.78), and minor (OR 3.30) adverse events (p<.0001 for all).Stratifying by medications being taken (and relative to those without RA), there was increasing odds of all adverse events (AAE) based on potency of medications (no biologic or disease modifying antirheumatic drugs [DMARDs] OR 2.33, DMARDs only OR 3.86, biologic±DMARDs OR 5.69 (p<.0001 for all). Despite this, no statistically significant difference in 5-year survival from subsequent lumbar surgery was found between those with versus without RA (p=.1000). CONCLUSIONSLumbar discectomy patients with RA were found to be at significantly higher risk for 90-day adverse events following lumbar discectomy, and this was incrementally greater for those on increasingly suppressive medications. Lumbar discectomy patients with RA bear specific consideration and perioperative monitoring when considered for lumbar discectomy.

Patient satisfaction with medication in rheumatoid arthritis: an unmet need.

Shared decision-making between rheumatologists and patients has become an overarching principle in current treatment recommendations in rheumatoid arthritis (RA). Therefore, in the present study, we aimed to assess the satisfaction of patients with RA with their treatment and to investigate the associated factors. A cross-sectional study was carried out in the Rheumatology Department of Mongi Slim Hospital. We included adults with RA receiving their current disease-modifying anti-rheumatic drugs for at least 12 months.Satisfaction among patients was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM) and it was defined by a score ≥ 80%. The factors indirectly influencing patient satisfaction that were assessed were: satisfaction with medical care management, disease activity, functional impact, professional impact, and the impact of RA. Multivariable regression analysis was applied to determine the predictors of satisfaction. We included 70 patients (63 female/7 male) with a mean age of 57.8 ±10.6 years. The mean disease duration was 13.71 ±7.2 years.Mean TSQM scores were 65.42 ±14.77 for convenience, 68.71 ±18 for effectiveness, 70.60 ±24.5 for side effects, and 67.95 ±17.10 for global satisfaction. Satisfaction rates were: 20% for convenience, 39% for effectiveness, 46% for side effects and 30% for global satisfaction.In multivariable analysis, the predictors of global dissatisfaction were Rheumatoid Arthritis Impact of Disease (RAID) overall score (p = 0.003) and the degree of physical difficulties (p = 0.001). Satisfaction with the physician was correlated with better global satisfaction (p = 0.029). Difficulties in adapting to RA (p = 0.043) and current treatment with biologics (p = 0.027) were predictors of dissatisfaction with convenience. Predictors of dissatisfaction with efficiency were the RAID overall score (p = 0.032) and the difficulties of adapting to RA (p = 0.013). The predictors of satisfaction with side effects were a lower degree of interference with domestic work (p = 0.02) and better involvement of the patient in the treatment decision (p = 0.014). The satisfaction with the attending physician, the participation in the treatment decision, and the impact of RA seem to influence treatment satisfaction the most. These data suggest that a better understanding of patients' medical needs and preferences would improve satisfaction outcomes.

Efficacy and safety of electroacupuncture combined with medication for rheumatoid arthritis: A systematic review and meta-analysis

ObjectiveThe aim of this study was to evaluate the effect of electroacupuncture (EA) combined with medication on clinical efficacy, pain scores (Visual Analogue Scale, [VAS]), Disease Activity Score in 28 joints (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and adverse events in treating patients with rheumatoid arthritis (RA). MethodsA systematic search of PubMed, the Cochrane Library, Web of Science, Embase, SinoMed, China National Knowledge Infrastructure, Wanfang, and VIP until December 12, 2021 was used to identify randomized controlled trials (RCTs) on the EA treatment of RA. Study selection and data extraction were performed critically and independently by two reviewers. Cochrane criteria for risk of bias was used to evaluate the methodological quality of the trials. The Grading of Recommendations Assessment, Development, and Evaluation Methodology (GRADE) was applied to assess the quality of evidence from quantitative analysis. ResultsSeventeen RCTs, including 1317 patients, satisfied the inclusion criteria. Compared with the control group, EA combined with medication had a superior effect on clinical efficacy (RR = 1.25 [95% CI = 1.18 to 1.33], P < 0.00001), VAS score (MD = −1.34 [95% CI = −1.90 to −0.78], P < 0.00001), DAS28 (MD = −0.76 [95% CI = −1.08 to −0.44], P < 0.00001), CRP level (SMD = −1.46 [95% CI = −2.19 to −0.74], P < 0.0001), and ESR (MD = −7.74 [95% CI = −13.77 to −1.72], P = 0.01). Compared with the control group, the meta-analysis showed no significant changes in adverse events in the EA group (RR = 1.08 [95% CI = 0.51 to 2.25], P = 0.85). The evidence level of the results from the 17 studies was very low to moderate. ConclusionsEA combined with medication showed a superior effect than Western medicine alone in clinical efficacy, VAS, DAS28, CRP, and ESR. The clinical safety of EA warrants further investigation in experimental studies.

Copay assistance use and prescription abandonment across race, ethnicity, or household income levels for select rheumatoid arthritis and oral oncolytic medicines.

BACKGROUND: Disparities in prescription abandonment may exacerbate health inequities. Whether copay assistance is associated with changes in prescription abandonment across different patient groups is unknown. OBJECTIVE: To assess disparities in copay assistance use; prescription abandonment across race, ethnicity, or income; and association of copay use with prescription abandonment and whether it differs across race, ethnicity, or household income. METHODS: This pooled, cross-sectional study assessed claims-level prescription data linked to a consumer database containing information on race, ethnicity, and household income for commercially insured patients. The first prescription for rheumatoid arthritis (RA) or oral oncolytic medicines from 2016 to 2020 was included. Logistic regression models measured odds of copay assistance use (copay/discount cards or free-trial voucher) and prescription abandonment (prescription not filled within 30 days of health plan approval). Interaction terms for copay assistance use by race, ethnicity, and income were tested. RESULTS: The sample included 67,674 patients prescribed RA medications and 9,560 prescribed oral oncolytic medications. Copay assistance use across race, ethnicity, and income ranged from 28.2% to 31.1% (RA medicines) and 27.2% to 36.7% (oral oncolytic medicines). Among those prescribed RA medicines and not using copay assistance, Black/African American, Hispanic patients, and those with household incomes less than $50,000 were more likely to abandon prescriptions than White patients and patients with household incomes more than $200,000 (odds ratio [OR] [95% CI], P value: Black/African American: 1.17 [1.06-1.29], P < 0.01; Hispanic: 1.11 [1.01-1.22], P = 0.03; income <$50,000: 1.24 [1.11-1.37], P < 0.01). Among patients using oral oncolytic medicines and not using copay assistance, there was no racial or ethnic difference in prescription abandonment. Patients using oral oncolytics with household incomes less than $50,000 were more likely to use copay assistance (1.34 [1.12-1.61], P < 0.01), but also more likely to abandon their prescriptions if not using copay assistance (1.44 [1.12-1.85], P < 0.01). Copay assistance was associated with a 79% (RA) and 71% (oral oncolytics) lower odds of prescription abandonment (0.21 [0.19-0.24], P < 0.01; 0.29 [0.24-0.36], P < 0.01), which did not differ across race, ethnicity, or income levels (P > 0.05). CONCLUSIONS: Copay assistance has potential to narrow disparities in prescription abandonment for commercially insured Black/African American or Hispanic patients taking RA medicines and patients with household incomes less than $50,000; however, efforts to improve access to copay assistance are needed. Copay assistance, as a factor facilitating equal access to medicines, is an important consideration when evaluating policies that impact access to copay assistance programs. DISCLOSURES: Genentech, Inc., provided funding and support for this study. Dr Wong is an employee of Genentech, Inc., and shareholder of Roche, Inc. Ms Donahue, Mr Thiesen, and Mr Yeaw are employees of IQVIA.

Nano Methotrexate versus Methotrexate in Targeting Rheumatoid Arthritis.

Nanomedicine has emerged as an important approach for targeting RA medication. Rheumatoid arthritis (RA) is a widespread autoimmune disorder marked by multiple inflamed joints. Gold nanoparticles (GNPs) have been demonstrated as efficacious nanocarriers due to their unique characteristics and the relative simplicity of their synthesis in varied sizes; moreover, they have the capability to alleviate several inflammatory markers. The current objective was to combine methotrexate (MTX) with GNPs to overcome MTX restrictions. GNPs were fabricated by a chemical reduction technique, utilizing sodium citrate and tween 20. The MTX-GNPs formulations were characterized in vitro by % entrapment efficiency (%EE), particle size, polydispersity index (PDI) zeta potential, and % release. The MTX-GNPs formulation was administrated as an intra-articular solution, and additionally, incorporated into a Carbopol gel to investigate its anti-arthritic effectiveness and bioavailability in vivo. The results indicated that a %EE of 87.53 ± 1.10%, and a particle size of 60.62 ± 2.41 nm with a PDI of 0.31 ± 0.03, and a zeta potential of -27.80 ± 0.36 mV were optimal. The in vitro release of MTX from the MTX-GNPs formulation demonstrated that the MTX-GNPs formulation's release was 34.91 ± 1.96% and considerably (p &lt; 0.05) lower than that of free MTX, showing a significant difference in dissolution patterns (p &lt; 0.05). In vivo, MTX-GNPs formulations inhibited IL-6 by 36.52%, ACCP (63.25 %), COMP (28.16%), and RANKL (63.67%), as well as elevated IL-10 by 190.18%. Transdermal MTX-GNPs decreased IL-6 by 22.52%, ACCP (56.63%), COMP (52.64%), and RANKL (79.5%), as well as increased IL-10 by 168.37%. Histological investigation supported these recent findings. Conclusions: Marked improvements in MTX anti-arthritic effects are seen when it is conjugated to GNPs.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p= .006), being male (p= .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p= 0.008) and high (DAS28 > 5.1) (p= 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p> 0.05). This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

The economic burden of biologic disease-modifying antirheumatic drugs in rheumatoid arthritis patients in the United States

Background Previous U.S. economic burden estimates for rheumatoid arthritis (RA) varied from $85.6 to 148.1 billion annually. However, these estimates do not reflect comparative amounts spent on RA treatment options in addition to other medical expenditures. Therefore, this study’s goal was to comparatively analyze the overall economic burden of U.S. patients treated for RA using conventional disease-modifying antirheumatic drugs (DMARDs) versus TNF alpha biologic DMARDs. Research Design and Methods This retrospective observational study analyzed Medical Expenditure Panel Survey Household Component data from 2016 to 2018. Healthcare utilization, total medical expenditures, and out-of-pocket expenditures were compared between RA medication groups. Results Three hundred twenty-five adult RA patients experiencing 603 RA-related events, including at least one medical visit, between 2016 and 2018 were identified. Rheumatic arthritis-attributable medical expenditures among patients prescribed DMARDs were $11.4 billion. Average total medical expenditures were significantly higher for the TNF alpha biologic group $26,216.67 (95% CI: $19,502.84–$32,930.5) versus $5,388.52 (95% CI: $2,768.25–$8,008.79) for the conventional DMARD group (p<0.001). Conclusions RA patients receiving TNF alpha biologics experienced significantly higher total medical and out-of-pocket expenditures; however, they have experienced fewer or no occurrences of high-cost drivers of healthcare utilization compared to patients receiving conventional DMARDs.

Complications After Open Reduction and Internal Fixation for Distal Radius Fractures in Patients With and Without Rheumatoid Arthritis

Rheumatoid arthritis (RA) can have severe impact on patients' functional abilities and increase the risk of fragility fractures. Little is known about how patients with RA fare after operative management of distal radius fractures. The purpose of this study was to compare postoperative complications after surgical fixation in patients with RA and controls, hypothesizing that patients with RA would have higher levels of postoperative complications. Patients were identified using Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Revision, codes for open treatment of distal radius fractures and RA at 3 level 1 trauma centers over a 5-year period (2015-2019). Chart abstraction provided details regarding injuries and treatment. Age- and sex-matched controls were identified in a 2:1 ratio. Postoperative complications were classified according to the Clavien-Dindo-Sink classification system and divided into early (less than 90 days) and late groups. Sixty-four patients (21 with RA and 43 controls) were included. The patients were predominantly women, with a mean age of 62 years and a mean Charlson comorbidity index of 2.1. The RA medications at the time of injury included conventional synthetic disease-modifying antirheumatic drugs (5/21), biologic disease-modifying antirheumatic drugs (5/21), or chronic oral prednisone (6/21). Rheumatoid medications, except hydroxychloroquine, were withheld for 2-3 weeks after surgery. Rheumatoid patients were significantly more likely to sustain a complication compared with the control group, although this was no longer significant on adjusted analysis. Class I complications were the most common. The incidence of early versus late complications was similar between the groups. A high rate of early return to surgery for fixation failure occurred in the RA group compared with none in the control group. Patients with RA undergoing operative management of distal radius fractures are at risk of postoperative complications, particularly fracture fixation failure, necessitating return to the operative room. High levels of pain, stiffness, and mechanical symptoms were noted in the RA group. Prognostic IV.