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ID PMID Title PublicationDate abstract
34100377 circ-PTTG1IP/miR-671-5p/TLR4 axis regulates proliferation, migration, invasion and inflamm 2021 May Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.
31705724 Coronary Microvascular Dysfunction in Rheumatoid Arthritis Compared to Diabetes Mellitus a 2021 Feb OBJECTIVE: Coronary microvascular dysfunction (CMD) is a predictor of cardiac death in diabetes mellitus (DM) independent of traditional cardiovascular (CV) risk factors. Rheumatoid arthritis (RA) is a chronic inflammatory condition, with excess CV risk compared to the general population, in which CMD is hypothesized to play a role; however, there are limited data on CMD in RA and any association with clinical outcomes. The objective of this study was to compare the prevalence of CMD in RA to that in DM and to test the association with all-cause mortality. METHODS: We performed a retrospective cohort study using data from a registry of all patients undergoing stress myocardial perfusion positron emission tomography as part of routine clinical care from 2006 to 2017. The inclusion criterion was a normal perfusion scan. Patients with RA or DM were classified using previously published approaches. Coronary flow reserve (CFR) was calculated for all patients in the registry and linked with mortality data. CMD was defined as CFR <2.0. RESULTS: We studied 73 patients with RA and 441 patients with DM. Among patients with a normal perfusion scan, the prevalence of CMD in RA was similar to that in DM (P = 0.2). CMD was associated with increased risk for all-cause mortality in RA (hazard ratio 2.4 [95% confidence interval 1.4-4.2]) as well as increased risk for cardiac-related death at rates similar to those in DM. CONCLUSION: These findings suggest an important role for CMD as a potential contributor to excess CV risk and mortality in RA, as previously observed in DM, as well as evidence for a mechanistic link between inflammation and cardiovascular disease.
33475311 Patient-Reported and Radiographic Outcomes of Joint-Preserving Surgery for Rheumatoid Fore 2021 Mar 17 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disorder and a chronic inflammatory disease that can damage joints throughout the body. As dramatic improvements in medical treatment have contributed to reduced progression of joint destruction, surgical methods for the treatment of RA-related forefoot deformities have gradually changed from joint-sacrificing to joint-preserving. The aim of this study was to assess the long-term outcomes, including patient-reported outcomes, of joint-preserving surgery for forefoot deformities associated with RA. METHODS: This retrospective study included 105 feet in 89 patients with RA who were treated during the period of January 2012 to May 2015 and had a minimum of 5 years of follow-up (mean, 6.0 ± 0.9 years). The patient-reported outcome measure used was the Self-Administered Foot Evaluation Questionnaire (SAFE-Q), which was completed preoperatively and at the latest follow-up (n = 53 feet). The hallux valgus angle (HVA), the intermetatarsal angle (IMA), and the position of the medial sesamoid were measured preoperatively, at 3 months postoperatively, and at the latest follow-up. Cases of delayed wound-healing, hallux valgus recurrence, nonunion at the osteotomy sites, and reoperation were recorded. Kaplan-Meier survival curves were used to determine the estimated survivorship, with reoperation as the end point. RESULTS: Scores of all 5 subscales of the SAFE-Q demonstrated significant improvement at the latest follow-up. The average HVA and IMA decreased significantly 3 months postoperatively, and these measurements remained significantly lower than the preoperative values (p < 0.01). The position of the medial sesamoid at the latest follow-up improved significantly (p < 0.01). Delayed wound-healing was found at the site of surgery in 21 (20.0%) of the 105 feet. Recurrence of hallux valgus was observed in 11 (10.5%) of the feet. There was no case of nonunion at any osteotomy site. Eleven (10.5%) of the feet required reoperation. The estimated survivorship of the studied joint-preserving surgery at 7 years, with reoperation as the end point, was 89.5%. CONCLUSIONS: Satisfactory long-term patient-reported and radiographic outcomes after joint-preserving surgery for forefoot deformities associated with RA can be achieved. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
33848332 Discontinuation of biologic DMARDs in a real-world population of patients with rheumatoid 2021 Dec 24 OBJECTIVES: Data from randomized controlled trials have shown the feasibility of discontinuation of bDMARD therapy in patients with RA that have reached remission. Criteria for selecting patients that are likely to remain in remission are still incompletely defined. We aimed to identify predictors of successful discontinuation of bDMARD therapy in the Swiss Clinical Quality Management (SCQM) registry, a real-world cohort of RA patients. METHODS: RA patients in DAS28-ESR remission who stopped bDMARD/tsDMARD treatment were included. Loss of remission was defined as a DAS28-ESR > 2.6 or restart of a bDMARD/tsDMARD. Time to loss of remission was the main outcome. Kaplan-Meier methods were applied and Cox regression was used for multivariable analyses adjusting for confounding factors. Missing data were imputed using multiple imputation. RESULTS: A total of 318 patients in a bDMARD/tsDMARD-free remission were followed between 1997 and 2017. In total, 241 patients (76%) lost remission after a median time of 0.9 years (95% CI: 0.7, 1.0). The time to loss of remission was shorter in women, in patients with a longer disease duration >4yrs and in patients who did not meet clinical disease activity index (CDAI) remission criteria at baseline. Remission was longer in patients with csDMARD therapy during b/tsDMARD free remission [hazard ratio (HR) 0.8, P =0.05, 95% CI: 0.6, 1.0]. CONCLUSION: In a real-world patient population, the majority of patients who discontinued b/tsDMARD treatment lost remission within <1 year. Our study confirms that fulfilment of more rigorous remission criteria and csDMARD treatment increases the chance of maintaining b/tsDMARD-free remission.
33188696 Changes in the illness perceptions of patients with rheumatoid arthritis over the first ye 2021 May 14 OBJECTIVES: To describe the illness perceptions of patients with RA over the first year of MTX treatment, and the association between illness perceptions and outcomes. METHODS: Data came from the Rheumatoid Arthritis Medication Study (RAMS), a UK multicentre cohort study of RA patients starting MTX for the first time. Patients were assessed at baseline, and at 6 and 12 months. Patients completed the Brief Illness Perception Questionnaire (B-IPQ) at each assessment, as well as other patient-reported outcomes (PROs). The inflammation score (2-component DAS28) was calculated. Subgroups of patients with similar trajectories across the eight (B-IPQ) items were identified using a latent class growth model. Predictors of group membership were identified using multinomial logistic regression. Associations between subgroups and PROs over follow-up were assessed using linear mixed models. RESULTS: Three subgroups were identified in the analysis population (N = 1087): Positive illness perceptions (N = 322), Negative illness perceptions (N = 534) and Improvers (N = 231) who switched from negative to positive illness perceptions over follow-up. Baseline disability was associated with group membership [Positive vs Negative: relative risk ratio (RRR) 0.37, 95% CI: 0.25, 0.54; Improvers vs Negative: RRR 0.60, 95% CI: 0.43, 0.83], as were other PROs (pain, fatigue, anxiety, depression). The Negative group had worse disability, pain and fatigue over follow-up compared with the other groups, controlling for inflammation. CONCLUSION: Negative illness perceptions are associated with poor PROs over time. The Improvers subgroup illustrated that illness perceptions can change in RA. Illness perceptions represent a potential therapeutic target that should be assessed using randomized trials.
34423769 An open-label, multiple-dose study to assess the preliminary pharmacokinetics, pharmacodyn 2021 Nov BACKGROUND: The pharmacokinetics, safety, and clinical activity of antibodies targeting CD22 have been evaluated in systemic lupus erythematosus (SLE) and non-Hodgkin lymphoma (NHL) patients, however, there have been no reports for the rheumatoid arthritis (RA) population. SM03 is a novel chimeric IgG1 monoclonal antibody which targets the B-cell-restricted antigen CD22. This is the first study of the anti-CD22 antibody in RA patients. OBJECTIVES: This study was designed to preliminarily evaluate the pharmacokinetics, pharmacodynamics, safety, and clinical activity profiles of the anti-CD22 monoclonal antibody SM03 in Chinese patients with active RA. MATERIALS AND METHODS: This study was an open phase I study in 8 RA patients. Eligible patients received two 600 mg doses of SM03 administered through intravenous infusions given 2 weeks apart and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical responses. RESULTS: After multiple doses of SM03, the maximum serum concentration of SM03 was reached within 2 - 4 hours. Mean elimination half-life was 16 days (range: 13 - 22 days). Half of the patients responded according to ACR and DAS28 assessments, and CD19(+) B lymphocyte counts decreased. Upper respiratory tract infections and headaches were the most common adverse events (AEs). No drug-related serious AEs were reported. CONCLUSION: This study is the first to report on the preliminary pharmacokinetics, pharmacodynamics, clinical activity, and safety of SM03 in RA patients. All AEs were mild or moderate in severity. SM03 showed potential efficacy in RA patients.
34496952 Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conven 2021 Sep 8 BACKGROUND: Understanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry. METHODS: This was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004-2007, 2008-2011, and 2012-2015. RESULTS: This study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004-2007 period; 38.6% and 38.2%, respectively, in the 2008-2011 period; and 35.2% for both in the 2012-2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012-2015 vs 2004-2007 and 2008-2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry. CONCLUSIONS: Increased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012-2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.
33629324 Radiotherapy in cancer and rheumathoid arthritis patients: cancer treatment or control of 2021 Feb OBJECTIVE: The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of >20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively. RESULTS: Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity. CONCLUSIONS: In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.
33314699 Association Between Bone Mineral Density and Autoantibodies in Patients With Rheumatoid Ar 2021 Jun OBJECTIVE: Autoantibodies, such as anti-citrullinated protein antibodies (ACPAs), have been described as inducing bone loss in rheumatoid arthritis (RA), which can also be reflected by bone mineral density (BMD). We therefore examined the association between osteoporosis and autoantibodies in two independent RA cohorts. METHODS: Dual x-ray absorptiometry (DXA) of the lumbar spine and left hip was performed in 408 Dutch patients with early RA during 5 years of follow-up and in 198 Swedish patients with early RA during 10 years of follow-up. The longitudinal effect of ACPAs and other autoantibodies on several BMD measures was assessed using generalized estimating equations. RESULTS: In the Dutch cohort, significantly lower BMD at baseline was observed in ACPA-positive patients compared to ACPA-negative patients, with an estimated marginal mean BMD in the left hip of 0.92 g/cm(2) (95% confidence interval [95% CI] 0.91-0.93) versus 0.95 g/cm(2) (95% CI 0.93-0.97) (P = 0.01). In line with this, significantly lower Z scores at baseline were noted in the ACPA-positive group compared to the ACPA-negative group (estimated marginal mean Z score in the left hip of 0.18 [95% CI 0.08-0.29] versus 0.48 [95% CI 0.33-0.63]) (P < 0.01). However, despite clear differences at baseline, ACPA positivity was not associated with greater decrease in absolute BMD or Z scores over time. Furthermore, there was no association between BMD and higher levels of ACPAs or other autoantibodies (rheumatoid factor and anti-carbamylated protein antibodies). In the Swedish cohort, ACPA-positive patients tended to have a higher prevalence of osteopenia at baseline (P = 0.04), but again, ACPA positivity was not associated with an increased prevalence of osteopenia or osteoporosis over time. CONCLUSION: The presence of ACPAs is associated with significantly lower BMD at baseline, but not with greater BMD loss over time in treated RA patients. These results suggest that ACPAs alone do not appear to contribute to bone loss after disease onset when disease activity is well-managed.
34732329 IRAK4 inhibitor mitigates joint inflammation by rebalancing metabolism malfunction in RA m 2021 Dec 15 Recent studies show a connection between glycolysis and inflammatory response in rheumatoid arthritis (RA) macrophages (MΦs) and fibroblasts (FLS). Yet, it is unclear which pathways could be targeted to rebalance RA MΦs and FLS metabolic reprogramming. To identify novel targets that could normalize RA metabolic reprogramming, TLR7-mediated immunometabolism was characterized in RA MΦs, FLS and experimental arthritis. We uncovered that GLUT1, HIF1α, cMYC, LDHA and lactate were responsible for the TLR7-potentiated metabolic rewiring in RA MΦs and FLS, which was negated by IRAK4i. While in RA FLS, HK2 was uniquely expanded by TLR7 and negated by IRAK4i. Conversely, TLR7-driven hypermetabolism, non-oxidative PPP (CARKL) and oxidative phosphorylation (PPARγ) were narrowly dysregulated in TLR7-activated RA MΦs and FLS and was reversed by IRAK4i. Consistently, IRAK4i therapy disrupted arthritis mediated by miR-Let7b/TLR7 along with impairing a broad-range of glycolytic intermediates, GLUT1, HIF1α, cMYC, HK2, PFKFB3, PKM2, PDK1 and RAPTOR. Notably, inhibition of the mutually upregulated glycolytic metabolites, HIF1α and cMYC, was capable of mitigating TLR7-induced inflammatory imprint in RA MΦs and FLS. In keeping with IRAK4i, treatment with HIF1i and cMYCi intercepted TLR7-enhanced IRF5 and IRF7 in RA MΦs, distinct from RA FLS. Interestingly, in RA MΦs and FLS, IRAK4i counteracted TLR7-induced CARKL reduction in line with HIF1i. Whereas, cMYCi in concordance with IRAK4i, overturned oxidative phosphorylation via PPARγ in TLR7-activated RA MΦs and FLS. The blockade of IRAK4 and its interconnected intermediates can rebalance the metabolic malfunction by obstructing glycolytic and inflammatory phenotypes in RA MΦs and FLS.
33123921 Risk of serious infection, malignancy, or death in Japanese rheumatoid arthritis patients 2021 May To evaluate whether combinatorial use of abatacept (ABT) and tacrolimus (Tac) increases the risk of adverse events compared to their individual use in Japanese rheumatoid arthritis (RA) patients. We conducted a retrospective cohort study of RA patients using the Japanese multicenter database and analyzed the data of RA patients registered from April 2010 to March 2019 by comparing three treatment groups who received Tac, ABT, or a combination of both. We included patients who had initiated treatment with ABT or Tac and excluded patients who used tumor necrosis factor inhibitors, IL-6 inhibitors, and Jak inhibitors in the first year of our study. The primary outcome was the occurrence of adverse events such as infections that required hospitalization, newly diagnosed malignancy, or death from any cause after initiation of ABT or Tac. Of the 27,032 RA patients in the registry, 2009 patients were included. The Tac, ABT, and combination groups consisted of 1328, 563, and 118 patients, respectively. Primary outcome occurred in 149 (13.4%), 62 (13.5%), and 14 (13.9%) patients of the Tac, ABT, and combination groups, respectively. The incidence of adverse events between groups was not significantly different (p = 0.638). A Cox regression analysis which was adjusted for potential confounders such as age, disease activity, and concomitant use of prednisolone revealed no significant differences between groups. The combinatorial use of ABT and Tac, or ABT alone does not increase the risk of adverse events when compared to the use of Tac alone in RA patients in Japan. Key Points • This study included Japanese rheumatoid arthritis data and found that there was no significant risk when patients were treated with a combination of Tac and ABT or each drug alone.
34618606 The risk of tuberculosis infection in 410 Saudipatients receiving adalimumab therapy. 2021 Sep BACKGROUND: Adalimumab is a fully humanized monoclonal antibody inhibitor of tumor necrosis factor-a used to treat various autoimmune disorders. Adalimumab poses a risk for tuberculosis (TB) infection, especially in countries where TB is endemic. OBJECTIVE: Determine the rate of TB infection after adalimumab therapy in Saudi Arabia. DESIGN: Medical record review. SETTINGS: Tertiary care center in Riyadh. PATIENTS AND METHODS: Demographic and clinical data were retrieved from the electronic healthcare records of all patients who received adalimumab treatment from 2015 to 2019. MAIN OUTCOME MEASURES: Occurrence of TB after adalimumab therapy. SAMPLE SIZE: 410 patients (median ([QR] age, 37 [28], range 4-81 years), 40% males RESULTS: Rheumatoid arthritis was the most frequent indication (n=153, 37%). The patients were followed for a mean of 36 (8.9) months. No case of TB infection or reactivation was observed. An inter-feron-gamma release assay (IGRA) was requested in 353/391 (90.3%) patients, prior to initiating therapy. The IGRA was positive in 26 cases (6.6%). The IGRA-positive patients received isoniazid prophylactically. Bacterial infectious complications of adalimumab therapy occurred in 12 (2.9%) patients. Urinary tract infection was the most frequent complication (culture requested in 48 patients, positive in 8). CONCLUSION: Adalimumab treatment was not associated with a risk of TB disease or TB reactivation in our cohort over the follow-up observation period. No TB reactivation occurred with adalimumab therapy when TB prophylaxis was used. The positive IGRA rate in patients on adalimumab treatment was low (7%). LIMITATIONS: Single center and one geographical area in Saudi Arabia. CONFLICT OF INTEREST: None.
33507948 Views of Mexican outpatients with rheumatoid arthritis on sexual and reproductive health: 2021 BACKGROUND: Rheumatoid arthritis (RA) impacts sexual and reproductive health (SRH), which is a prominent component of a patient´s quality of life and highly influenced by the cultural background. The aim of the study was to explore the interest of Mexican outpatients with RA in SRH and to examine patient view on SRH. METHODS: This cross-sectional study surveyed 303 consecutive outpatients with RA on their perceptions of SRH importance, SRH satisfaction, access to SRH information, preferences regarding SRH communication with healthcare professionals, and understanding of SRH (qualitative open-ended descriptions). Descriptive statistics and inferential analysis were used. Patient knowledge of each dimension of SRH was rated based on pre-specified criteria. Two assessors assigned ten major themes to each patient´s description of both dimensions of SRH. RESULTS: Patients perceived their SRH as an important component of their general health and wished to address the topic, although few had access to such communication. Female patients assigned lesser importance to SRH, showed lesser degree of satisfaction with SRH, and expressed preference for a truthful physician. Age showed a linear association with individual survey responses, except for satisfaction with reproductive health dimension. There was a linear association between increased age and decreased years of formal education with a lower level of SRH knowledge. Ten major themes emerged for each of the two dimensions of the SRH construct, although most individual descriptions were assigned to one or two major themes. CONCLUSIONS: Further education and assessment of SRH in Mexican patients with RA is warranted.
33560301 Non-adherence in difficult-to-treat rheumatoid arthritis from the perspectives of patients 2021 Nov 3 OBJECTIVES: Treatment non-adherence is more frequent among difficult-to-treat (D2T) than among non-D2T RA patients. Perceptions of non-adherence may differ. We aimed to thematically structure and prioritize barriers to (i.e. causes and reasons for non-adherence) and facilitators of optimal adherence from the patients' and rheumatologists' perspectives. METHODS: Patients' perceptions were identified in semi-structured in-depth interviews. Experts selected representative statements regarding 40 barriers and 40 facilitators. Twenty D2T and 20 non-D2T RA patients sorted these statements during two card-sorting tasks: first, by order of content similarity and, second, content applicability. Additionally, 20 rheumatologists sorted the statements by order of content applicability to the general RA population. The similarity sorting was used as input for hierarchical cluster analysis. The applicability sorting was analysed using descriptive statistics, prioritized and the results compared between D2T RA patients, non-D2T RA patients and rheumatologists. RESULTS: Nine clusters of barriers were identified, related to the healthcare system, treatment safety/efficacy, treatment regimen and patient behaviour. D2T RA patients prioritized adverse events and doubts about effectiveness as the most important barriers. Doubts about effectiveness were more important to D2T than to non-D2T RA patients (P = 0.02). Seven clusters of facilitators were identified, related to the healthcare system and directly to the patient. All RA patients and rheumatologists prioritized a good relationship with the healthcare professional and treatment information as the most helpful facilitators. CONCLUSIONS: D2T RA patients, non-D2T RA patients and rheumatologists prioritized perceptions of non-adherence largely similarly. The structured overviews of barriers and facilitators provided in this study may guide improvement of adherence.
33593531 Aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles alleviate inflammatio 2021 Apr 15 Rheumatoid arthritis (RA) is a chronic autoimmune disorder and serious cause of disability. Despite considerable advances in RA management, challenges like extensive drug metabolism and rapid clearance causes poor bioavailability. Core-shell nanocarriers for co-delivery of glycyrrhizic acid (GA) and budesonide against RA were developed. GA-loaded gelatin nanoparticles (NPs) were synthesized and coated with budesonide encapsulated aminocellulose-grafted polycaprolactone (PCL-AC). GA- and budesonide-loaded PCL-AC-gel NPs had diameter of 200-225 nm. Dual drug-loaded (DDL) NPs reduced joint swelling and erythema in rats while markedly ameliorating bone erosion evidenced by radiological analysis, suppressed collagen destruction, restored synovial tissue, bone and cartilage histoarchitecture with reduced inflammatory cells infiltration. NPs also reduced various inflammatory biomarkers such as TNF-α, IL-1β, COX-2, iNOS. Results of this study suggest that dual NPs exerted superior therapeutic effects in RA compared to free drugs which may be attributed to slow and sustained drug release and NPs' ability to inhibit inflammatory mediators.
34588273 In vitro evaluation of disease-modifying antirheumatic drugs against rheumatoid arthritis 2021 Sep OBJECTIVES: In the past, the human microbiome has consistently been associated with rheumatoid arthritis (RA) and disease activity. Here, we investigate the antimicrobial activity of disease-modifying antirheumatic drugs (DMARDs) against typical representatives of the oral microflora that have been associated with RA. METHODS: DMARDs were screened for antimicrobial activity against bacteria that are associated with the pathogenesis of the disease and/or frequently isolated from the oral microflora of patients with RA. Screening was done by an agar diffusion assay and minimum inhibitory concentrations (MICs) of antimicrobial active substances were then determined by broth dilution. RESULTS: Aurothiomalate and sulfasalazine demonstrated broad-spectrum antimicrobial activity, but with MICs ranging from 18 to >280 µg/mL and 150 to >600 µg/mL, respectively, only at supratherapeutic concentrations. Methotrexate showed antimicrobial activity only against Fusobacterium nucleatum and Viridans streptococci. The corresponding MICs were 3.75 to >30 µg/mL and 0.5-15 µg/mL, respectively, thus at least for streptococci, within the therapeutically achievable range. No other DMARD tested showed antimicrobial activity in the agar diffusion screening assay. CONCLUSION: Methotrexate, sulfasalazine and aurothiomalate showed antimicrobial activity against a broad spectrum of RA associated pathogens of the oral microflora. While methotrexate showed relevant antimicrobial activity, and to a more limited extent aurothiomalate, sulfasalazine was active only at far supratherapeutic systemic concentrations. Nevertheless, given the highly species-dependent antimicrobial activity and the multiple ways it can affect the human microbiome, our results suggest a link between antimicrobially active antirheumatic drugs and their potential effect in the treatment of RA.
32928503 Effectiveness of a self-management program for joint protection and physical activity in p 2021 Apr BACKGROUND: Rheumatoid arthritis is a chronic, systemic disease, which results in progressive destruction of the joints and a reduction in quality of life. Joint protection can minimize injuries that worsen arthritis and pain and certain activities can help patients control or reduce the symptoms of this chronic disease. OBJECTIVES: To determine the effectiveness of a self-management program for joint protection and physical activity for patients with rheumatoid arthritis based on self-efficacy theory. DESIGN: A two-arm (experimental vs control) randomized trial. PARTICIPANTS: Adult patients with rheumatoid arthritis were recruited from rheumatology departments of a medical center in Northern Taiwan. A total of 224 patients met the inclusion criteria and agreed to participate in the study. METHODS: Eligible participants with rheumatoid arthritis were randomly assigned to either an 8-week program in self-management of joint protection and physical activity with nursing support (intervention group, n = 112) or standard care for rheumatology (control group, n = 112). Outcome variables were assessed at baseline and 2-, 3-, and 6-months after commencement of the intervention, which included measures of disease activity, and self-assessments for self-efficacy, quality of life, and self-management behaviors. Differences in outcome variables over time between the groups were analyzed with generalized estimating equations; the level of significance was set at p < 05. RESULTS: The mean age of participants was 58.8 years, duration of the rheumatoid arthritis was 10 years, and most participants (86%) were female. Characteristics and assessment variables did not differ between the two groups at baseline. When compared with the control group at 6 months following initiation of the self-management program, participants in the intervention group demonstrated significantly greater improvement in physical functioning (B = 4.08, p < 05), self-efficacy of pain (B = 4.89, p < .05), and self-management behaviors (B = 4.65, p < 05). CONCLUSIONS: A self-management program based on self-efficacy theory that focused on joint protection and physical activities resulted in significant improvements in physical functioning, self-efficacy, and self-management behaviors 6 months following commencement of the intervention. Nurses provided individualized evaluations and support, which may have made it easier for participants to learn and perform the activities. After commencement of participation in the intervention, no improvements were seen until 6 months of participation. This delay may suggest patients with chronic disease may need a longer duration of self-management training and increased follow-up time to incorporate lifestyle changes. Future studies measuring long-term outcomes are suggested.
34641582 Common Factors of Alzheimer's Disease and Rheumatoid Arthritis-Pathomechanism and Treatmen 2021 Oct 5 The accumulation of amyloid plaques, or misfolded fragments of proteins, leads to the development of a condition known as amyloidosis, which is clinically recognized as a systemic disease. Amyloidosis plays a special role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease, and rheumatoid arthritis (RA). The occurrence of amyloidosis correlates with the aging process of the organism, and since nowadays, old age is determined by the comfort of functioning and the elimination of unpleasant disease symptoms in the elderly, exposure to this subject is justified. In Alzheimer's disease, amyloid plaques negatively affect glutaminergic and cholinergic transmission and loss of sympathetic protein, while in RA, amyloids stimulated by the activity of the immune system affect the degradation of the osteoarticular bond. The following monograph draws attention to the over-reactivity of the immune system in AD and RA, describes the functionality of the blood-brain barrier as an intermediary medium between RA and AD, and indicates the direction of research to date, focusing on determining the relationship and the cause-effect link between these disorders. The paper presents possible directions for the treatment of amyloidosis, with particular emphasis on innovative therapies.
33673487 Diet in Rheumatoid Arthritis versus Systemic Lupus Erythematosus: Any Differences? 2021 Feb 27 In recent years, an increasing interest in the influence of diet in rheumatic and musculoskeletal diseases (RMDs) led to the publication of several articles exploring the role of food/nutrients in both the risk of developing these conditions in normal subjects and the natural history of the disease in patients with established RMDs. Diet may be a possible facilitator of RMDs due to both the direct pro-inflammatory properties of some nutrients and the indirect action on insulin resistance, obesity and associated co-morbidities. A consistent body of research has been conducted in rheumatoid arthritis (RA), while studies in systemic lupus erythematosus (SLE) are scarce and have been conducted mainly on experimental models of the disease. This review article aims to outline similarities and differences between RA and SLE based on the existing literature.
33722955 Meaningful Change Thresholds for Patient-Reported Outcomes Measurement Information System 2021 Aug OBJECTIVE: We estimated meaningful change thresholds (MCTs) for Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue and Pain Interference in rheumatoid arthritis (RA). METHODS: The responsiveness of several patient-reported outcomes (PROs) was assessed among 521 patients with RA in the Arthritis, Rheumatism, and Aging Medical Information Systems (ARAMIS) cohort. PROMIS Fatigue (7-item) and Pain Interference (6-item) short form instruments were administered at baseline, 6 months, and 12 months. Self-reported retrospective changes over the previous 6 months (a lot better/worse, a little better/worse, stayed the same) were obtained at 6 and 12 months' follow-up. We estimated MCTs using the mean change in PROMIS scores for patients who rated their change "a little better" or "a little worse." RESULTS: Baseline fatigue and pain interference scores were near normal (median 54 and 56, respectively). At 6 months, 7.9% of patients reported their fatigue was a little better compared to baseline (mean change [SD]: -2.6 [4.8]) and 22.8% a little worse (1.7 [5.6]). Pain was a little better for 11.5% of patients (-1.9 [6.1]) and a little worse for 24.2% of patients (0.6 [5.7]). At 12 months, results were similar. Thus, the MCT range was 1-2 points for both fatigue and pain interference. Correlations between change scores and retrospective ratings were low (0.13-0.29), indicating possible underestimation of MCT. CONCLUSION: The group-level MCT for PROMIS Fatigue and Pain Interference is roughly 2-3 points and corresponds to a small effect size, which is consistent with earlier work demonstrating an MCT of 2 points for PROMIS Physical Functioning.