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ID PMID Title PublicationDate abstract
32784608 Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical A 2020 Aug 7 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.
32371434 Impending radiographic erosive progression over the following year in a cohort of consecut 2020 May BACKGROUND/PURPOSE: To evaluate biomarkers as predictors of impending erosion progression. METHODS: Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations. RESULTS: Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP). CONCLUSIONS: Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.
31494241 Are key cytokines genetic and serum levels variations related to rheumatoid arthritis clin 2020 Jan 5 This study evaluated the possible association between SNPs in cytokines coding genes, namely IL10, IL6 and IFNG, cytokines serum levels and clinical assessment' scores in patients with Rheumatoid Arthritis(RA). SNPs genotyping was performed in 126 RA patients and 177 healthy individuals with Taqman probes specific for IL10 -1082 (T>C, rs1800896);INFG -1616 (A>G, rs2069705) and IL6 -174 (G>C, rs1800795) variants,positioned in regulatory regions. Cytokine Bead Array (CBA) was used to measure cytokine levels. We found association between INFG -1616 G allele(p = 0.0210; OR = 1.605) and INFG -1616 GG genotype (p = 0.0268; OR =2.609) and RA susceptibility. We also observed association between IL10 -1082 TT genotype and high clinical disease activity index (CDAI) values (p = 0.026; OR = 1.906; 95% CI = 1.082 - 3.359), IL10 -1082 CC genotype and low CDAI values (p = 0.016; OR = 0.256) and INFG -1616 AA and high CDAI values (p = 0.025; OR = 2.919). IL10 -1082 CC also exhibited the lowest IL-10 levels than IL10 -1082 TT (p = 0.020) and IL10 -1082 TC (p = 0.032). Finally, we verified higher IL-6 value in the RA patients than healthy control group (p = 0.007) and an association between high IL-6 levels and increased CDAI (r = 0.4648, p = 0.0015); DAS 28 (r = 0.3933, p= 0.0091), presence of bone erosions (r = 0.3170, p = 0.0361), ESR levels(r = 0.3041, p = 0.0448) and IFN-γ levels (r = 0.3049, p = 0.0468).Altogether, we suggest that IL10 -1082 (T>C, rs1800896) and INFG -1616(A>G, rs2069705) polymorphisms as well as IL-6 levels alterations may play a role for prognostic and disease follow-up.
32967487 Serum 14-3-3η is a Marker that Complements Current Biomarkers for the Diagnosis of RA: Ev 2022 Jan OBJECTIVE: To systematically evaluate the diagnostic value of 14-3-3η protein for rheumatoid arthritis (RA). METHOD: Searched PubMed, Web of Science, Embase and China Biology Medicine (CBM) databases comprehensively from inception to May 2020. The evaluation index were the pooled sensitivity, specificity, diagnosis odds ratio (DOR), positive likelihood ratio (PLR), negative likelihood ratio (NLR), as well as the area under the summary receiver operating characteristic (SROC) curves. Meta-Disc 1.4 and RevMan 5.3 were used to analyze all statistics. QUADAS-2 tool was applied to evaluate the quality of eligible studies. Subgroup analysis and meta-regression were used to explore the sources of heterogeneity. RESULTS: Nine articles containing eleven records were eligible for this meta-analysis. The pooled sensitivity of 14-3-3η was 0.63 (95% CI: 0.60 to 0.66), the pooled specificity was 0.90 (95% CI: 0.88 to 0.91). The pooled PLR and NLR was 6.10 (95% CI: 4.67 to 7.96) and 0.40 (95% CI: 0.33 to 0.48), respectively. The pooled DOR was 15.90 (95% CI: 11.15 to 22.68), and the area under the curve (AUC) was 0.8696. Compared with a single indicator (rheumatoid factor or anti-citrullinated protein antibodies), adding 14-3-3η can bring incremental benefits to the diagnosis of RA. The results of subgroup analysis and meta-regression suggested that the two factors (ethnicity, early vs established RA) we analyzed might not be the source of heterogeneity (P value were 0.0979 and 0.4298, respectively) and there was no publication bias among these articles (P = .42). CONCLUSION: Serum 14-3-3η protein is a supplementary biomarker in the diagnosis of RA.
32279574 High density lipoprotein in rheumatoid arthritis: emerging role in predicting inflammation 2020 Sep Dyslipidaemia is common in patients with rheumatoid arthritis (RA) appearing both early and advanced stages of the disease. A retrospective study was designed to explore the clinical significance of high density lipoprotein (HDL) in Chinese patients with RA. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL) and low density lipoprotein (LDL) were compared between RA patients complicated with osteoporosis (OP) and without OP, using logistic regression and ROC curve to analyse the association of HDL with OP. C reactive protein (CRP), erythrocyte sedimentation rate(ESR), rheumatoid factor(RF), anti-cyclic citrulline polypeptide antibody (anti-CCP), 28 joints disease activity(DAS28) as well as organ involvement rates were then analysed between RA patients with different HDL levels. Serum levels of HDL were 1.2 ± 0.3 mmol/L in RA patients complicated with OP, significantly higher than those without OP; HDL was a risk factor for RA patients with OP, OR (95% CI) being 10.2 (4.5-23.0) after adjusting for gender, age and body mass index(BMI). RA patients with HDL ≤ 1.04 mmol/L had significantly higher levels of CRP, ESR, DAS28 and cardiovascular disease (CVD) incidence rate, yet OP incidence rate was lower. HDL was a predictor of RA-related OP, indicating potential value as predictor of disease complications in RA patients.
32141529 A review of network meta-analysis comparing biologics in the treatment of rheumatoid arthr 2020 Feb OBJECTIVE: Even though in recent years significant improvements have been made in the management of patients with rheumatoid arthritis due to the introduction of biologic agents, it is still difficult to identify the most effective and safest available treatment. The choice and comparison between biological agents are a challenge, for only limited head-to-head clinical studies are available. The aim of this manuscript is to review the published network meta-analysis (NMA) to gain a better understanding of efficacy and safety of biological agents and small molecules in the management of RA patients. MATERIALS AND METHODS: We used MEDLINE and EMBASE to identify network meta-analyses from 2008 to June 2019 comparing efficacy and safety of licensed biological agents and tsDMARDS at the approved dosages using predefined text words related to the topic. The following scenarios have been investigated: patients not responding to csDMARD (cDMARDs - IR); csDMARD naïve patients; patients not responding to biologics (bDMARDs - IR); patients in biological monotherapy. RESULTS: On the basis of the data present in the literature, we are able to hypothesize some trends of response in terms of efficacy in different subsets of patients, for example patients in monotherapy, bDMARds unresponsive patients, and Methotrexate-naive patients. The differences of the results presented in many works are due to the different inclusion criteria used in the studies, the type of biologics agent used in each study (according to the available molecules in the different years of publication), as well as differences in the methodology of NMA and in the presentation of the data. CONCLUSIONS: We suggest that the next NMA follows the indications suggested by the Professional Society for Health Economics and Outcomes Research (ISPOR) so that the results are comparable and comprehensible.
33201766 Immune Function and Mechanism of Costimulating Molecules PD-1 and OX40 in Rheumatoid Arthr 2020 Nov Rheumatoid arthritis (RA) is a T lymphocyte-mediated autoimmune disease, although its immune mechanism has not been fully studied. In this study, healthy controls (HC), osteoarthritis patients (OA), and RA patients were enrolled, and mice were evenly divided into control, collagen-induced arthritis (CIA), PD-1 Fc/CIA (PD-1 Fc membrane fusion protein administered to CIA mice), OX40 Fc/CIA (OX40 Fc membrane fusion protein administered to CIA mice), and PD-1 Fc + OX40 Fc/CIA groups. The expressions of programmed death-1 (PD-1) and OX40 in CD4(+) T lymphocytes and the levels of sPD-1, immunoglobulin, and proinflammatory factors in patients and mice were measured. The results showed that the expression levels of PD-1 and OX40 in CD4(+) T lymphocytes separated from the peripheral blood and synovial fluid of RA patients and the spleen of CIA mice were observably elevated. The levels of soluble PD-1, interleukin (IL)-2, IL-4, IL-5, IL-17, and interferon-γ (IFN-γ) in RA patients obviously increased. In animal experiments, PD-1 Fc not only increased the serum levels of immunoglobulin G (IgG), IgG1, and IgG2a in CIA mice, but also increased the levels of IL-4, IL-2, IL-5, IL-17, and IFN-γ in mouse spleen cells and joint tissues, which, however, were reversed by OX40 Fc. In conclusion, OX40 inhibition could reverse the progression of RA caused by PD-1 blocking, and PD-1 might be a potential target for RA. Clinical Trials.gov ID: HGH2018012203.
32449040 Disease activity and patient-reported outcomes in patients with rheumatoid arthritis and S 2020 Aug The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjögren's syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (± 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for ≥ 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA.
32036488 Cardiovascular MRI evidence of reduced systolic function and reduced LV mass in rheumatoid 2020 Mar The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference - 2.86% (- 5.17, - 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p < 0.001) and lower late/active diastolic strain rate (p < 0.001) compared to controls. There was evidence of reduced LV mass index (LVMI) (- 4.56 g/m(2) (- 8.92, - 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.
34625148 Musculoskeletal disorders due to chikungunya virus: A real experience in a rheumatology de 2021 Oct BACKGROUND: Chikungunya (CHIKV), is an endemic RNA virus in some regions of Asia and Africa. In Colombia in 2014, its spread started explosively and quickly. The presentation of CHIKV is a febrile condition, with musculoskeletal symptoms, which can progress to erosive arthropathy and polyarticular deformity. The purpose of this study is to evaluate symptomatic and serological behaviour in patients suffering from CHIKV infection in Neiva, Huila who attend the Rheumatology clinic, and to describe the comorbidities associated with the chronic phase of the disease. METHODS: An observational, longitudinal and retrospective analysis of data collected in 410 patients afflicted with the CHIKV virus, with symptoms lasting more than 3 months, who persisted with musculoskeletal and joint symptoms. The patients were classified according to their commitment in post-viral arthralgias, polyarthritis post viral, Rheumatoid Arthritis (RA) post CHIKV, Spondyloarthritis postCHIKV, and soft tissue rheumatism. The statistical analysis was performed using SPSS software (version 24). A descriptive analysis was carried out to evaluate quantitative variables such as the mean (standard deviation), and categorical variables such as frequency (%). The categorical variables were compared using the Chi-square equation. As a statistical significance, a p less than .05 was considered. RESULTS: Of the 410 patients, 89.23% were women, with polyarticular involvement in 92.26% of the cases. Of the patients, 49.83% had osteoarthritis. At the time of the evaluation in the Rheumatology clinic, 46.3% of the cases presented persistent non-inflammatory arthralgias, and 53.7% of the patients underwent arthritis on physical examination, of which, remarkably, 20.3% met the criteria for rheumatoid arthritis postCHIKV. CONCLUSIONS: The development of musculoskeletal symptoms after CHIKV infection is a very serious public health problem, with persistent complications and long-term morbidity risk in real life. The presence of net postviral arthritis is noteworthy, however the development of postCHIKV rheumatoid arthritis usually requires more advanced pharmacological measures, including, in some cases, transition to biological therapy. The presence of symptoms of venous insufficiency in the lower limbs that developed with CHIKV infection was an incidental finding that requires a more precise study.
33191276 Priorities for High-quality Care in Rheumatoid Arthritis: Results of Patient, Health Profe 2021 Apr OBJECTIVE: To elucidate the essential elements of high-quality rheumatoid arthritis (RA) care in order to develop a vision statement and a set of strategic objectives for a national RA quality framework. METHODS: Focus groups and interviews were conducted by experienced qualitative researchers using a semistructured interview or focus group guide with healthcare professionals, patients, clinic managers, healthcare leaders, and policy makers to obtain their perspectives on elements essential to RA care. Purposive sampling provided representation of stakeholder types and regions. Recorded data was transcribed verbatim. Two teams of 2 coders independently analyzed the deidentified transcripts using thematic analysis. Strategic objectives and the vision statement were drafted based on the overarching themes from the qualitative analysis and finalized by a working group. RESULTS: A total of 54 stakeholders from 9 Canadian provinces participated in the project (3 focus groups and 19 interviews). Seven strategic objectives were derived from the qualitative analysis representing the following themes: (1) early access and timeliness of care; (2) evidence-informed, high-quality care for the ongoing management of RA and comorbidities; (3) availability of patient self-management tools and educational materials for shared decision making; (4) multidisciplinary care; (5) patient outcomes; (6) patient experience and satisfaction with care; and (7) equity, the last of which emerged as an overarching theme. The ultimate vision obtained was "ensuring patient-centered, high-quality care for people living with rheumatoid arthritis." CONCLUSION: The 7 strategic objectives that were identified highlight priorities for RA quality of care to be used in developing the National RA Quality Measurement Framework.
31756165 Autoimmune polyglandular syndrome type 3 variant in rheumatoid arthritis. 2020 Mar 1 INTRODUCTION: Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant. CASE REPORT: A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves' disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy. CONCLUSION: In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.
33205322 Safety and Effectiveness of Biologic Disease-Modifying Antirheumatic Drugs in Older Patien 2020 Dec BACKGROUND AND OBJECTIVE: The number of older patients with rheumatoid arthritis is increasing, but data on drug effectiveness and safety in these patients are scarce. This study assessed the effectiveness and safety of biologic disease-modifying antirheumatic drugs in older patients with rheumatoid arthritis. METHODS: This prospective cohort study was based on data recorded in the Rheumatic Diseases Portuguese Register (Reuma.pt). Treatment persistence, European League Against Rheumatism response at 6 and 12 months, and adverse events were compared between adult (age < 65 years), old (age 65-74 years), and very old (age ≥ 75 years) patients. RESULTS: In total, 2401 patients were included, of which 379 were old and 83 were very old. Older patients had higher disease activity at baseline (Disease Activity Score 28: 5.5 in adults, 5.7 in old patients, and 6 in very old patients; p = 0.02) and more comorbidities, with patients aged 65-74 years beginning biologic disease-modifying antirheumatic drugs later in the course of rheumatoid arthritis. Treatment persistence was similar in the three patient groups (p = 0.07). The European League Against Rheumatism response rates were comparable in the three groups at 6 months (81.6% of adults, 75.2% of old patients, and 81.8% of very old patients; p = 0.19), and inferior in old patients at 12 months. The proportion of patients who experienced adverse events was also similar in the three groups (21% of adults, 22.5% of old patients, and 22.9% of very old patients; p = 0.76), but the rate of serious adverse events was higher in old patients (1.94/100 patient-years) and very old patients (4.29/100 patient-years) compared with 1.03/100 patient-years in adult patients with rheumatoid arthritis (p < 0.05). CONCLUSIONS: Adults, old patients, and very old patients with rheumatoid arthritis benefit similarly from biologic disease-modifying antirheumatic drug treatments, although older patients have more active disease at baseline and more comorbidities. However, it is necessary to consider the risk of serious adverse events in older patients when prescribing a biologic.
31566133 The Study of Natural Compounds Targeting RANKL Signaling Pathway for the Treatment of Bone 2020 Millions of people, especially for the aging people, are suffered by bone-loss diseases, such as rheumatoid arthritis (RA) and osteoporosis. Therefore, better understanding the involved mechanisms of bone metabolism is required for further treat on such diseases. Particularly, during the pathological process of bone losing, RANKL as a member of the tumor necrosis factor (TNF) superfamily, could induce osteoclast precursor cells differentiate into mature osteoclast, which grant its essential role in osteolysis. In recent years, with the increased attention paid to the natural compounds discovering studies, the therapeutic application of natural plant-derivatives have been widely recognized. Therefore, our present study aim to summarize the current novel research progressions on RANKL and its downstream signaling pathways in bone cellular differentiation, and provide a further insight for RANKL as the important drug targets in bone loss diseases. Besides that, in our current study, we also aim to briefly introduce the current application of several natural compounds for treating RANKL-mediated osteoclastic activation by modulating the RANKL signaling pathway and their therapeutic effects on the prevention of osteoporosis, osteoarthritis (OA) and RA.
32222381 Glucocorticoid-trials in rheumatoid arthritis mostly study representative real-world patie 2020 Dec OBJECTIVE: Randomized controlled trials (RCTs) are considered the gold standard in clinical research due to credible causality. Their results, however, may not be generalizable to real-world populations. While glucocorticoids (GCs) remain a mainstay of rheumatoid arthritis (RA) treatment, it is unclear whether the results of GC-RCTs are generalizable to current real-world RA patients. METHODS: MEDLINE was searched for RCTs and, as comparators, cohort studies (CSs) in RA evaluating systemic GCs. Random-effects meta-analyses were performed for descriptive baseline characteristics (including general demographics, comorbidities, and disease activity) that have been shown to be able to modify the benefit-risk-ratio of various RA therapeutics. These meta-analyses were stratified by study type (RCT and CS). Stratified estimates were subsequently compared. Further sensitivity analyses were performed stratifying by disease duration. RESULTS: 56 RCTs (7053 participants) and 10 CSs (14,688 participants) were included. 12 characteristics were reported frequently enough to allow for comparative analysis. In 10/12 characteristics (83%), RCT estimates did not appear to differ from CS estimates. However, RCT participants were younger (-4.7 years [95% CI -7.2 to -2.1]; p < 0.001) and had higher erythrocyte sedimentation rates (11.8 mm/h [5.7 to 17.8]; p < 0.001) than CS participants. Comorbidities could not be assessed due to insufficient reporting. CONCLUSION: Our findings suggest that evidence from GC trials in RA is of acceptable generalizability to current real-world patients - especially compared to findings from biologic agents in RA. However, RCT participants were younger than real-world patients, potentially limiting the generalizability of trial results to elderly patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42019134675).
33379138 Electrochemical Immunosensor for the Early Detection of Rheumatoid Arthritis Biomarker: An 2020 Dec 28 Rheumatoid arthritis (RA) is a chronic autoimmune disease that produces a progressive inflammatory response that leads to severe pain, swelling, and stiffness in the joints of hands and feet, followed by irreversible damage of the joints. The authors developed a miniaturized, label-free electrochemical impedimetric immunosensor for the sensitive and direct detection of arthritis Anti-CCP-ab biomarker. An interdigitated-chain-shaped microelectrode array (ICE) was fabricated by taking the advantage of microelectromechanical systems. The fabricated ICE was modified with a self-assembled monolayer (SAM) of Mercaptohexanoic acid (MHA) for immobilization of the synthetic peptide bio-receptor (B-CCP). The B-CCP was attached onto the surface of SAM modified ICE through a strong avidin-biotin bio-recognition system. The modified ICE surface with the SAM and bio-molecules (Avidin, B-CCP, Anti-CCP-ab and BSA) was morphologically and electrochemically characterized. The change in the sensor signal upon analyte binding on the electrode surface was probed through the electrochemical impedance spectroscopy (EIS) property of charge-transfer resistance (R(ct)) of the modified electrodes. EIS measurements were target specific and the sensor response was linearly increased with step wise increase in target analyte (Anti-CCP-ab) concentrations. The developed sensor showed a linear range for the addition of Anti-CCP-ab between 1 IU mL(-1) → 800 IU mL(-1) in phosphate buffered saline (PBS) and Human serum (HS), respectively. The sensor showed a limit of detection of 0.60 IU mL(-1) and 0.82 IU mL(-1) in the PBS and HS, respectively. The develop bio-electrode showed a good reproducibility (relative standard deviation (RSD), 1.52%), selectivity and stability (1.5% lost at the end of 20th day) with an acceptable recovery rate (98.0% → 101.18%) and % RSD's for the detection of Anti-CCP-ab in spiked HS samples.
32814987 Adaptation and validation of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnair 2020 Dec Rheumatoid arthritis (RA) is a chronic disease with an enormous impact on patients' quality of life. The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is a disease-specific measure of QoL for individuals with rheumatoid arthritis. Our aim was to adapt and validate the RAQoL for use in Bulgaria. The development of a new language version of the RAQoL consisted of three stages: translation, field testing and psychometric evaluation. The dual-panel methodology, requiring two independent panels of Bulgarian speakers, was applied to translate the UK English version of the RAQoL into Bulgarian. Face and content validity of the translated questionnaire were assessed through cognitive debriefing interviews. Lastly, the RAQoL was administered on two occasions to a random sample of RA patients to evaluate reliability and validity. At the first occasion, the SF-36 was also administered for use as a comparator scale. The RAQoL was successfully adapted into Bulgarian and considered easy to understand, acceptable and comprehensive by RA patients. A psychometric study demonstrated that the new language version has excellent internal consistency (Cronbach's alpha coefficients = 0.93 and 0.94) and test-retest reliability (a Spearman's rank correlation coefficient = 0.97). Convergent validity was established by correlating scores on the RAQoL with a comparator measure, the SF-36. A strong correlation between RAQoL scores and the physical functioning section of the SF-36 was observed. Known group validity was established by the ability of the measure to distinguish between subgroups of patients, who differed according to their perceived general health, disease severity (p < 0.001) and whether they were experiencing a flare-up (p < 0.01). The new language version is recommended for use in future research studies, clinical trials and routine practice with Bulgarian RA patients.
31600025 Perceived Stress and Inflammatory Arthritis: A Prospective Investigation in the Studies of 2020 Dec OBJECTIVE: The aim of this study was to determine the association of perceived stress with incident inflammatory arthritis (IA) defined as having at least 1 joint consistent with rheumatoid arthritis (RA)-like synovitis based on examination. METHODS: We conducted a prospective cohort study in the Studies of the Etiologies of Rheumatoid Arthritis cohort. Participants without IA were recruited if they were a first-degree relative of an RA proband or screened positive for anti-citrullinated protein antibody. Perceived stress was measured using the Perceived Stress Scale-14 (PSS-14), in which scores can range from 0 to 56, and a higher score indicates greater perceived stress. The total PSS-14 score, as well as 2 subscores indicative of perceived distress and self-efficacy, were averaged across all study visits until development of IA or the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of IA associated with average PSS-14 scores were obtained using Cox proportional hazards models. RESULTS: The mean total PSS-14 score was 20.4. We found that a 1-point increase in the perceived distress score was significantly associated with a 10-percent increase in the risk of IA (adjusted HR 1.10 [95% CI 1.02-1.19]). Total PSS-14 and self-efficacy were not associated with IA risk (adjusted HR 1.05 [95% CI 0.99-1.10] and 1.04 [95% CI 0.91-1.18], respectively). CONCLUSION: An association between perceived distress and incident IA was observed in this at-risk cohort. Replication of this finding in other preclinical and at-risk RA populations is needed.
31843461 Auxiliary in vitro and in vivo biological evaluation of hydrogen peroxide sensitive prodru 2020 Jan 15 Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes severe joints damage and other extra-articular alterations. Despite the efficacy of low-dose methotrexate (LD-MTX) in RA treatment, adverse effects are the predominant reasons for discontinuation of therapy. As a therapeutic targeting strategy, the presence of increased concentrations of reactive oxygen species (ROS) in the inflammatory environment can serve as the stimulus for prodrug activation in site-selective drug delivery systems. Our group has previously reported novel ROS sensitive prodrugs (1-3) of MTX and aminopterin (AMT) for site-selective delivery to inflammatory tissue associated with RA, with the aim of reducing side effects in RA therapy. Herein, we investigate the effect and toxicity of the same prodrugs in a rat CIA (collagen-induced arthritis) model of RA. We find that prodrug 1, an arylboronic acid ROS-sensitive MTX-prodrug, displays similar in vivo efficacy as MTX at an equimolar dose, while avoiding adverse effects known to restrict MTX treatment. To further characterize prodrug 1 and its ROS mediated activation, we synthesized compound 4, a negative control lacking the boronic acid moiety. We then investigated the effect of molecules on cell proliferation and cytotoxicity in the presence of the ROS scavenger pyruvate, as well as their stability in buffer and cell media, demonstrating a direct correlation between ROS concentration and the prodrug activity. Moreover, the in vitro ADME properties were investigated, including permeability, rat plasma and microsomal stability.
32876784 Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis. 2021 Apr OBJECTIVE: Most recommendations for the use of methotrexate (MTX) in rheumatoid arthritis (RA) are issued by developed countries. It is unknown whether they are relevant globally. We reviewed existing recommendations on the use of MTX for the treatment of RA and summarized areas of agreement that could be relevant for least developed countries (LDCs). METHODS: Electronic databases and registries were searched for recommendations on MTX use in RA, duplicates were eliminated, and the most updated version adopted when there were several versions on the same recommendation. Reviewers used the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for study quality assessment. Similarities and discrepancies of recommendations are reported. RESULTS: After deduplication, 1693 unique citations were found; 25 full texts were screened and 12 included in the narrative synthesis. Average scores for the AGREE II domains ranged from 33.3 to 83.3%. Recommendations targeted rheumatologists and health care providers involved in RA care. Most covered some but not all of the following areas: baseline "pre-MTX" assessment (7/12;58%), prescription of MTX (10/12;83.3%), management of MTX side effects (6/12;50%), and special considerations (e.g., peri-operative management) (8/12; 66.7%). Recommendations agreed on baseline tests prior to starting MTX, monitoring, and need for folic acid supplementation. These aspects can serve as the foundation for the development of MTX recommendations relevant to LDCs. Recommendations disagreed on the MTX starting dose, optimal route, titration, and intervals to monitor toxicity. CONCLUSION: Existing recommendations do not uniformly address all aspects related to the use of MTX and disagree in relevant aspects of MTX use. Adaptations to these recommendations are needed to facilitate their implementation in LDCs. Key Points • This paper summarizes current recommendations on the use of methotrexate for the treatment of rheumatoid arthritis. • Areas of agreement between recommendations include the following: pre-methotrexate patient assessment, need for folic acid supplementation, and toxicity monitoring. • Areas of disagreement relate to methotrexate starting and maximal dose, titration, and frequency of assessments.