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ID PMID Title PublicationDate abstract
32385878 Periodontitis and rheumatoid arthritis: An update 2012-2017. 2020 Jun Rheumatoid arthritis and chronic periodontitis are both chronic inflammatory diseases characterized by an exacerbated inflammatory reaction that leads to destruction of bone and other connective tissue. Owing to these similarities, the relationship between these two diseases has been investigated for over two decades. In the 2013 proceedings from a workshop jointly held by the European Federation of Periodontology and American Academy of Periodontology in 2012 it was concluded that there was at least minimal evidence of an association between periodontitis and rheumatoid arthritis. In this review, we consider publications in the field over the past 5 years and determine whether the evidence for this relationship has increased.
32840716 The Evaluation of (68)Ga-Citrate PET/CT Imaging for Dihydroartemisinin in the Treatment of 2021 Feb PURPOSE: We aimed to use (68)Ga-citrate, a labeled product of gallium (iron analog), combined with positron emission tomography/computed tomography (PET/CT) to non-invasively evaluate the potential of the iron-responsive product dihydroartemisinin (DHA) in the treatment of rheumatoid arthritis. PROCEDURES: From the establishment of chicken II collagen-induced arthritis (CIA) rat model over 40 days, 20 rats with one-to-one corresponding arthritis index (AI) scores were randomly divided into two groups. One group received oral DHA (at a dose of 1.5 ml/(kg day), containing 20 mg DHA per 1 ml) for 15 days; the other group received stroke-physiological saline solution (SSS, 1.5 ml/(kg day) for 15 days. (68)Ga-citrate micro-PET/CT imaging was performed on day 0 (D0), day 5 (D5), day 10 (D10), and day 15 (D15) of oral administration. After data reconstruction, the cross-sectional length "d" of the ankle joint of each rat was measured on the transverse CT, and the SUV(max) of the ankle joint and muscle background was measured for statistical analysis. After micro-PET/CT collection, the ankle joint tissue was observed by HE staining. RESULTS: The ankle joint swelling in the DHA group was significantly suppressed, but the SSS group showed no significant suppression. (68)Ga-citrate micro-PET/CT imaging results and microscope observation confirmed this finding. Statistical analysis indicated that the time tendency of AI score (B(interaction) = 0.495, P < 0.001) and T/NT (B(interaction) = 1.345, P < 0.001) were discrepant between DHA and SSS groups. The AI score and T/NT of the DHA group gradually increased with time, while the SSS group score gradually decreased. Furthermore, the Spearman correlation coefficient was used to describe the relationship between "d" and T/NT, which was positively correlated (r = 0.855, P < 0.001). CONCLUSIONS: This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer ((68)Ga-citrate).
31538511 Validation and assessment of minimally clinically important difference of the unadjusted H 2020 Jan Objectives: The Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) is a widely used patient-reported outcome for functional disability in rheumatoid arthritis (RA). Minimal clinically important differences (MCIDs) in the HAQ-DI were previously calculated based on device-corrected ordinal HAQ-DI scores, leading to limited generalizability and validity for today's patients. Our objectives were to examine the internal construct validity of the unadjusted HAQ-DI and to determine an MCID in a cohort of Danish RA patients based on the transformed linear logit scale of the HAQ-DI.Method: The study included 362 RA patients registered in the DANBIO registry. The Rasch model was fitted to HAQ-DI data at baseline and after 3 months' follow-up. MCID was calculated as the median changes in the original HAQ-DI score and logit HAQ-DI score in those patients who had experienced minimal improvement (15-30 mm on a 0-100 mm Patient Global scale).Results: HAQ-DI data showed acceptable fit to the Rasch model at both time-points, and consistent item ranking across time indicated instrument invariance. Sixty-one patients (16.8%, ~1/6) had an improvement above the MCID on the logit scale but improvement below the MCID on the original scale, while the opposite was not the case for any patients.Conclusions: The Danish unadjusted version of the HAQ-DI showed acceptable internal construct validity. Application of the logit MCID classified an additional one in six patients as having achieved an MCID compared to the MCID calculated on the ordinal scale, which may have potential implications for the powering of future studies.
32052146 Drug interactions in the treatment of rheumatoid arthritis and psoriatic arthritis. 2020 Apr BACKGROUND: Treating patients with inflammatory joint diseases (rheumatoid arthritis, psoriatic arthritis) according to established treatment algorithms often requires the simultaneous use of three or more medications to relieve symptoms and prevent long-term joint damage as well as disability. OBJECTIVE: To assess and give an overview on drug-drug interactions in the pharmacotherapy of inflammatory joint diseases with regards to their clinical relevance. METHODS: All possible drug combinations were evaluated using three commercially available drug interaction programs. In those cases where only limited/no data were found, a comprehensive hand search of Pubmed was carried out. Finally, the drug-drug interactions of all possible combinations were classified according to evidence-based medicine and a specifically generated relevance-based system. RESULTS: All three interaction software programs showed consistent results. All detected interactions were combined in clearly structured tables. CONCLUSION: A concise overview on drug-drug interactions is given. Especially in more sophisticated cases extensive knowledge of drug interactions supports optimisation of therapy and results in improved patient safety.
32609555 Golimumab improves socio economic and health economic parameters in patients with rheumato 2020 Sep BACKGROUND: Golimumab (GLM) has shown its efficacy and safety in various clinical trials. We aimed to assess the effect of GLM on socio economic and health economic parameters in daily clinical practice. SETTING: Rheumatology offices in Germany. METHOD: Analysis of socio economic and health economic parameters of the non-interventional, multicentre, prospective study GO-NICE. Analyses were performed in an exploratory manner using descriptive statistical methods. Further, p-values on socio economic variables were calculated based on one-sample t-test on the differences between baseline and follow-up visits. RESULTS: A total of 1458 patients were evaluable, of whom a total of 664 patients completed the 24-month observation period. The proportions of hospitalizations decreased statistically significantly (p ≤ .05) from 10.4/7.6/14.0% at baseline (BL) to 1.7/2.2/0.8%, and the in-patient rehabilitations decreased from 3.3/3.7/7.5% at BL to 0.6/1.8/2.1% at month 24 in patients with RA, PsA, and AS. When considering a 30-day period, the mean number of sick leave days decreased statistically significantly (p ≤ .005) from 4.0 at BL to 0.9 at month 24 (greatest improvement in RA), and the mean number of days with impaired capability decreased statistically significantly (p ≤ .001) from 14.9 at BL to 4.5 at month 24 (greatest improvement in patients with AS). There was also a reduction in the number of consultations and remedies. CONCLUSION: This evaluation shows improvements in socio economic and health economic parameters on GLM treatment.
32643484 Relationship between the physician-based clinical scale for foot and ankle surgery and pat 2021 May OBJECTIVES: To validate and establish targets for the physician-based clinical scale for foot surgery in rheumatoid arthritis (RA) patients based on patient-reported outcomes from a multicenter prospective cohort. METHODS: We collected data on demographics, values from the RA foot and ankle scale by the Japanese Society for Surgery of the Foot (JSSF-RA), and patient-reported outcomes (PROs) including the Health Assessment Questionnaire Disability Index (HAQ-DI) before (baseline) and 6 and 12 months after joint surgery. Target values for JSSF-RA were determined according to the lower limit of the 95% CI of JSSF-RA in patients with HAQ-DI ≤0.5 after adjusting for age and sex. We used multiple linear regression analysis to examine potential predictors of JSSF-RA target achievement at baseline. RESULTS: Cross-sectional analysis was conducted on data from 417 cases. The JSSF-RA target for foot and ankle surgery was set at 74 according to the JSSF-RA value corresponding to HAQ-DI ≤0.5 (mean 77.6, 95% CI: 74.3-80.9). Longitudinal analysis of patients who underwent foot surgery (N = 59) determined target cut-off values of 1.188 and 65 for HAQ-DI and JSSF-RA at baseline, respectively, as being predictive for achieving JSSF-RA ≥74 after surgery. CONCLUSIONS: A JSSF-RA value of 74 represents an important target for patients with RA who have undergone foot surgery. In order to achieve this target, the timing of the surgery should be considered in the treatment of established RA patients.
32888052 Doctor's aptitude for switching from innovator etanercept to biosimilar etanercept in infl 2021 Jan OBJECTIVES: To describe the switch to biosimilar etanercept (bETN), evaluate factors associated with this switch, and evaluate the efficacy of this switch in a real-life setting METHODS: We included patients, from October 2016 to April 2017, with rheumatoid arthritis (RA) and spondyloarthritis (SpA) who received innovator ETN (iETN) for at least 6 months. After receiving information on biosimilars, all physicians were invited to propose a switch from iETN to bETN. Factors associated with bETN discontinuation were explored by univariate and multivariate analyses. We estimated the proportion of patients still on bETN over time by Kaplan-Meier survival analysis. We assessed serum trough concentrations of iETN and bETN and anti-drug antibodies to ETN. RESULTS: Overall, 183 outpatients were eligible for a potential switch; 94 (51.6%) switched from iETN to bETN. The probability of a switch was greater with an older than younger aged physician (mean [SD] age 50.4 [14.3] with a switch vs 44.8 [11.3] with no switch, p = 0.005) and the physician having a full-time academic position than other position (56.4% with a switch vs 13.5% with no switch, p < 0.001). After a 6-month follow-up, bETN retention rate was 83% (95% CI: 0.76-0.92). The first cause of bETN discontinuation was inefficacy (50%). On multivariate analysis, no factor was independently associated with a bETN switch or discontinuation. Drug trough levels did not significantly differ by discontinuation or continuation of bETN. No patient showed anti-drug antibodies. CONCLUSION: The probability of switching from iETN to bETN was likely related to physician characteristics.
31879859 Effects of miR-150-5p on the growth and SOCS1 expression of rheumatoid arthritis synovial 2020 Mar OBJECTIVE: miR-150-5p has been implicated in the regulation and onset of immune diseases. We investigated the effects of miR-150-5p on the functions of RA synovial fibroblasts (RASFs). METHOD: The binding site between suppressor of cytokine signaling 1 (SOCS1) and miR-150-5p was analyzed using European Bioinformatics Institute database, and the 3' UTR of SOCS1 mRNA, including the binding site, was amplified and ligated to the 3'-end of LUC2 gene in the pmirGL0 dual-luciferase vector. The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5p mimics and the negative control (NC) mimics groups. Further, the RASF cell line MH7A was transfected with miR-150-5p or NC mimics and subjected to flow cytometric analysis, cell counting kit-8 assay, western blot analysis, qPCR, and enzyme-linked immunosorbent (ELISA) assay 48 h after transfection. RESULTS: miR-150-5p mimics resulted in a lower cell apoptotic rate and proportion of cells in the S phase. Using a dual-luciferase reporter gene assay, we then found that SOCS1 is a potential target of miR-150-5p. Compared with NC mimics, miR-150-5p mimics significantly decreased the protein and mRNA expression levels of SOCS1. ELISA assay showed that miR-150-5p mimics increased interleukin-6 level in the cell culture medium but did not influence tumor necrosis factor-alpha levels. CONCLUSIONS: Overall, the growth-promoting effect of miR-150-5p on MH7A cells may be attributed to the miR-150-5p-induced degradation of SOCS1 mRNA, suggesting a potential therapeutic target for RA.Key Points• SOCS1 is a potential target of miR-150-5p.• miR-150-5p promoted the growth of RASF cell line MH7A.• miR-150-5p increased the secretion of IL-6 but did not significantly affect TNF-α levels in MH7A cells.
32243398 Cardiovascular outcomes in patients with co-existing coronary artery disease and rheumatoi 2020 Apr BACKGROUND: Through this analysis, we aimed to systematically compare the cardiovascular outcomes observed in patients with co-existing coronary artery disease (CAD) and rheumatoid arthritis (RA). METHODS: Mendeley, Web of Science (WOS), MEDLINE, Cochrane central, EMBASE, Google scholar, and http://www.ClinicalTrials.gov were searched for English-based publications on CAD and RA. Selective cardiovascular outcomes were the endpoints in this analysis. The statistical software RevMan 5.3 was used for data assessment. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent each subgroup analysis. RESULTS: One thousand four hundred forty six (1446) participants had co-existing CAD and RA whereas 205,575 participants were in the control group (only CAD without RA). This current analysis showed that the risk of asymptomatic or stable angina was similar in CAD patients with versus without RA (RR: 0.98, 95% CI: 0.84 - 1.14; P = .78). However, all-cause mortality (RR: 1.47, 95% CI: 1.34 - 1.61; P = 0.00001), cardiac death (RR: 1.51, 95% CI: 1.05 - 2.17; P = .03) and congestive heart failure (RR: 1.41, 95% CI: 1.27 - 1.56; P = .00001) were significantly higher in CAD patients with RA. However, multi-vessel disease (RR: 2.03, 95% CI: 0.57 - 7.26; P = .28), positive stress test (RR: 1.69, 95% CI: 0.70 - 4.08; P = .24), and ischemic events (RR: 1.18, 95% CI: 0.81 - 1.71; P = .40) were similar in both groups. The risk for myocardial infarction, repeated revascularization, and the probability of patients undergoing percutaneous coronary intervention (PCI) (RR: 1.20, 95% CI: 0.75 - 1.93; P = .45) were also similar in CAD patients with versus without RA. When we considered outcomes only in those patients who underwent revascularization by PCI, all-cause mortality (RR: 1.43, 95% CI: 1.29 - 1.60; P = .00001) was still significantly higher in CAD patients with RA. CONCLUSIONS: This analysis showed a significantly higher mortality risk in CAD patients with RA when compared to the control group. Congestive heart failure also significantly manifested more in CAD patients with co-existing RA. However, the risks all the other cardiovascular outcomes were similar in both groups. Nevertheless, due to the several limitations of this analysis, this hypothesis should be confirmed in forthcoming trials based on larger numbers of CAD patients with co-existing RA.
32317314 Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum l 2020 Jul BACKGROUND: After adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment. OBJECTIVE: To validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders. METHODS: A diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity. RESULTS: 137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab. CONCLUSIONS: In contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.
32555299 Serum hepcidin level, iron metabolism and osteoporosis in patients with rheumatoid arthrit 2020 Jun 18 Hepcidin, a major regulator of iron metabolism and homeostasis, is regulated by inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis, and the aim of this study was to determine whether serum hepcidin levels are correlated with the degree of osteoporosis in patients with rheumatoid arthritis (RA). A total of 262 patients with RA (67.5 ± 11.4 years; 77.5% female) were enrolled. Serum iron, ferritin, and hepcidin levels were positively correlated each other. Multiple regression analyses revealed that the serum iron level was positively correlated with femoral T and Z scores, whereas the serum hepcidin level was not. Serum hepcidin level was correlated with the serum 25-hydroxy vitamin D level, which was in turn positively related to the femoral Z score. Serum hepcidin and serum iron were indirectly and directly related to osteoporosis in patients with RA.
32640149 Autoimmune Conditions: Rheumatoid Arthritis. 2020 Jul Rheumatoid arthritis (RA) is the most common autoimmune inflammatory arthritis, and is seen more commonly in women, smokers, and individuals with a family history of RA. It should be considered if unexplained pain and swelling in the metacarpophalangeal and/or metatarsophalangeal joints and morning stiffness of fingers lasting for longer than 30 minutes are present. RA may be present in the lungs, skin, and eyes. It is associated with an increased risk of cardiovascular death independent of other risk factors. Disease activity should be monitored using a validated scale, such as the Disease Activity Score 28 (DAS28), among others. Earlier management to achieve remission or decrease disease activity is associated with less joint damage, better quality of life, and improved survival rates. Methotrexate with consideration of low-dose glucocorticoids is considered first-line therapy for RA. Other disease-modifying antirheumatic drugs, including immunobiologics, may be used for patients who do not benefit from methotrexate. Before undergoing treatment, patients should be screened for tuberculosis and hepatitis B and C infection. Drug dosages may be tapered in patients with remission or decreased disease activity, but drugs should not be discontinued.
32813981 Value of serum collagen triple helix repeat containing-1(CTHRC1) and 14-3-3η protein comp 2021 Apr INTRODUCTION: Serological markers are important in the diagnosis of rheumatoid arthritis (RA) and other connective tissues diseases This study explored the clinical value of collagen triple helix repeat containing-1 (CTHRC1) and 14-3-3η protein, compared to routine markers, in the diagnosis of RA. METHODS: We recruited 103 RA patients, 105 non-RA patients (osteoarthritis, ankylosing spondylitis, systemic lupus erythematosus) and 59 healthy controls. CTHRC1, 14-3-3η, anti-cyclic citrullinated peptide antibody (anti-CCP), anti-mutated citrullinated vimentin antibody (anti-MCV), rheumatoid factor and erythrocyte sedimentation rate (ESR) levels were measured, and their diagnostic value for RA evaluated and compared. RESULTS: All laboratory indices were elevated in RA (P < 0.05). Of these, anti-MCV had the highest sensitivity (86.4%) and anti-CCP the highest specificity (94.5%). The areas under the curve (AUC) of CTHRC1, 14-3-3η, anti-CCP, anti-MCV, rheumatoid factor and ESR were 0.84, 0.81, 0.89, 0.91, 0.85 and 0.77 respectively (all P < 0.01). Anti-CCP and anti-MCV were the most valuable in the diagnosis of RA. The combination of anti-CCP and anti-MCV had the maximum Youden index, followed by the combination of anti-CCP and 14-3-3η. Binary logistic regression analysis showed that 14-3-3η had the largest odds ratio value (95% CI) at 5.1 (2.1-12.5) for RA. CONCLUSION: CTHRC1 and 14-3-3η are promising serological indicators of RA, and when combined with anti-CCP, anti-MCV and ESR, can improve the diagnosis of this disease.
33183527 Evaluating the relationship between dietary intake with inflammatory factors, lipid profil 2020 Dec BACKGROUND AND AIM: Rheumatoid arthritis (RA) is one of the most common life-threatening and associated with inflammation. The aim of this study was to evaluate the relation between dietary intake, inflammatory factors, lipid profile, medication and clinical outcomes in patients with rheumatoid arthritis. METHODS: This cross-sectional study were conducted in 72 patients with RA that referred to Rheumatology Clinic, Urmia, Iran. After describing the study and obtaining patient consent, fasting blood samples were collected from all participants in start stage, Nuclear Factor-Kappa B (NF-KB), Oxidized Low-Density Lipoprotein (Ox-LDL), lipid profile and clinical symptoms were record in participants. Also, Data on dietary intake and physical activity were collected with relevant questionnaires. RESULTS: There was a positive significant relation between energy intakes and low-density lipoprotein Cholesterol (LDL-C) (R = 0.855, P = 0.023), carbohydrate intake with total cholesterol (R = 0.297, P = 0.045), carbohydrate intake and NF-kB (R = 0.292, P = 0.017), fat intakes and Ox-LDL (R = 0.321, P = 0.027), prednisolone and Triglyceride (TG) (R = 0.378, P = 0.016), calcium supplement, folic acid and High-Density Lipoprotein Cholesterol (HDL-C) (R = 0.259, R = 0.34, R = 0.355, P = 0.09 respectively). In addition, the correlation between carbohydrate and energy intakes with HDL-C were negative significant (R = -0.355, P = 0.09 and R = -0.259, P = 0.034). SJC, Tender Joint Count (TJC), Erythrocyte Sedimentation Rate (ESR) and VAS were related to DAS28 and other variables shown no relation with DAS28. CONCLUSION: There are many factors affecting the clinical symptoms of patients with RA that attention to nutritional and medicinal factors can have a significant role in the clinical symptoms and complications of these patients.
33251808 Perspectives of Methotrexate-Based Radioagents for Application in Nuclear Medicine. 2021 Jan 4 Methotrexate is a gold standard among disease modifying antirheumatic drugs and is also extensively used clinically in combination with oncological therapies. Thus, it is not surprising that nuclear medicine found an interest in methotrexate in the search for diagnostic and therapeutic solutions. Numerous folate-related radiopharmaceuticals have been proposed for nuclear medicine purposes; however, methotrexate radioagents represent only a minority. This imbalance results from the fact that methotrexate has significantly weaker affinity for folate receptors than folic acid. Nevertheless, radiolabeled methotrexate agents utilized as a tool for early detection and imaging of inflammation in rheumatoid arthritis patients gave promising results. Similarly, the use of multimodal MTX-release nanosystems may find potential applications in radiosynovectomy and theranostic approaches in folate receptor positive cancers.
31504934 Interleukin-36 family dysregulation drives joint inflammation and therapy response in psor 2020 Apr 1 OBJECTIVES: IL-36 agonists are pro-inflammatory cytokines involved in the pathogenesis of psoriasis. However, their role in the pathogenesis of arthritis and treatment response to DMARDs in PsA remains uncertain. Therefore, we investigated the IL-36 axis in the synovium of early, treatment-naïve PsA, and for comparison RA patients, pre- and post-DMARDs therapy. METHODS: Synovial tissues were collected by US-guided biopsy from patients with early, treatment-naïve PsA and RA at baseline and 6 months after DMARDs therapy. IL-36 family members were investigated in synovium by RNA sequencing and immunohistochemistry, and expression levels correlated with DMARDs treatment response ex vivo. Additionally, DMARDs effects on IL-36 were investigated in vitro in fibroblast-like synoviocytes. RESULTS: PsA synovium displayed a reduced expression of IL-36 antagonists, while IL-36 agonists were comparable between PsA and RA. Additionally, neutrophil-related molecules, which drive a higher activation of the IL-36 pathway, were upregulated in PsA compared with RA. At baseline, the synovial expression of IL-36α was significantly higher in PsA non-responders to DMARDs treatment, with the differential expression being sustained at 6 months post-treatment. In vitro, primary PsA-derived fibroblasts were more responsive to IL-36 stimulation compared with RA and, importantly, DMARDs treatment increased IL-36 expression in PsA fibroblasts. CONCLUSION: The impaired balance between IL-36 agonists-antagonists described herein for the first time in PsA synovium and the decreased sensitivity to DMARDs in vitro may explain the apparent lower efficacy of DMARDs in PsA compared with RA. Exogenous replacement of IL-36 antagonists may be a novel promising therapeutic target for PsA patients.
32869404 Renegotiating dimensions of the self: A systematic review and qualitative evidence synthes 2020 Dec BACKGROUND: As chronic illnesses, such as rheumatoid arthritis (RA), place an increased burden on health-care systems, the ability of individuals to self-manage these diseases is crucial. OBJECTIVE: To identify and synthesize the lived experience of self-management described by adults living with RA. DESIGN: A systematic search of five electronic databases (MEDLINE, CINAHL, EMBASE, PsycINFO and ASSIA) was undertaken to identify relevant studies. Data were extracted and quality-assessed using CASP guidelines. A meta-synthesis was conducted based on Thomas and Harden's thematic synthesis approach. RESULTS: The search identified 8423 publications. After removing duplicates, 6527 records remained of which 32 studies met the inclusion criteria. Quality of studies was moderate to high, yet a considerable lack of reflection on researcher bias was evident. Our analysis identified 28 dimensions of self-management RA across six domains: (a) cognitive-emotional, (b) behavioural, (c) social, (d) environmental, (e) physical and (f) technological. Cognitive-emotional experiences dominated the analysis. Renegotiating 'the self' (self-concept, self-esteem, self-efficacy) was a key focus of self-management among individuals with RA. CONCLUSION: Our findings highlight the focus of 'the self' as a central concern in the self-management of RA. Standardized self-management programmes may primarily focus on disease management and daily functioning. However, we suggest that personal biographies and circumstances should move to the fore of self-management support. REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews 2018: CRD42018100450. PATIENT OR PUBLIC CONTRIBUTION: Patient and public involvement was not explicit in this review. However, three authors provided a patient perspective on the self-management of arthritis and autoimmune disease.
31556339 T cells, natural killer cells, and γδT cells in a large patient cohort with rheumatoid a 2020 Jan Objective: The aim of this cohort study was to evaluate the distribution of natural killer (NK) cells and T-cell subsets, including γδT cells, in the peripheral blood of patients with rheumatoid arthritis (RA) in a large real-life patient cohort, taking into account the patients' demographics, disease characteristics, and anti-rheumatic therapy.Method: The study recruited 508 RA patients between November 2013 and August 2015. Lymphocyte differentiation using eight-colour flow cytometry (fluorescence-activated cell sorting) of the peripheral blood was performed for all patients. Clinical data, including age, gender, disease duration, serostatus, disease activity, antibody status, immunosuppressive therapy including use of different biological disease-modifying anti-rheumatic drugs (bDMARDs) and conventional synthetic DMARDs, were retrospectively assessed using electronic patient files. Multivariate regression analysis was performed to assess the effect of these variables on T-cell, NK-cell, and γδT-cell counts.Results: The median patient age was 61.0 years and 74.1% were female. The median disease duration of RA was 12.0 years. Median Disease Activity Score based on 28-joint count was 2.8 and 56.3% were treated with bDMARDs. There were no differences in immunosuppressive therapy between different age groups. While rituximab, abatacept, and tocilizumab had no influence on lymphocyte subdifferentiation, tumour necrosis factor (TNF) inhibitors and age significantly influenced the numbers of T cells, T-helper cells, T-NK cells, NK cells, and γδT cells.Conclusion: Age and TNF-inhibition therapy influence lymphocyte subdifferentiation in patients with RA. It may be prudent to use age- and therapy-adjusted standard values for lymphocyte subsets during clinical trials and treatment of RA.
33203678 Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proin 2020 Dec 1 IL-17-producing Th17 cells are implicated in the pathogenesis of rheumatoid arthritis (RA) and TNF-α, a proinflammatory cytokine in the rheumatoid joint, facilitates Th17 differentiation. Anti-TNF therapy ameliorates disease in many patients with rheumatoid arthritis (RA). However, a significant proportion of patients do not respond to this therapy. The impact of anti-TNF therapy on Th17 responses in RA is not well understood. We conducted high-throughput gene expression analysis of Th17-enriched CCR6(+)CXCR3(-)CD45RA(-) CD4(+) T (CCR6(+) T) cells isolated from anti-TNF-treated RA patients classified as responders or nonresponders to therapy. CCR6(+) T cells from responders and nonresponders had distinct gene expression profiles. Proinflammatory signaling was elevated in the CCR6(+) T cells of nonresponders, and pathogenic Th17 signature genes were up-regulated in these cells. Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in nonresponders. Importantly, short hairpin RNA targeting USF2 in pathogenic Th17 cells led to reduced expression of proinflammatory cytokines IL-17A, IFN-γ, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as transcription factor T-bet. Together, our results revealed inadequate suppression of Th17 responses by anti-TNF in nonresponders, and direct targeting of the USF2-signaling pathway may be a potential therapeutic approach in the anti-TNF refractory RA.
33122725 Association between obesity and remission in rheumatoid arthritis patients treated with di 2020 Oct 29 The aim of this study was to investigate the association between body-mass index (BMI) and remission in RA patients receiving conventional synthetic (cs-) or the biological Disease-Modifying Antirheumatic Drug (DMARD), tocilizumab. Individual participant data (IPD) were pooled from five trials investigating tocilizumab and/or csDMARDs therapy (primarily methotrexate) for RA. Time to first remission was recorded according to the Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI). BMI was classified according to WHO definitions. Associations between baseline BMI and remission were assessed by Cox-proportional hazard analysis. IPD were available from 5428 patients treated with tocilizumab ± csDMARDs (n = 4098) or csDMARDs alone (n = 1330). Of these, 1839 (33.9%) had normal BMI, 1780 (32.8%) overweight, 1652 (30.4%) obese and 157 (2.9%) were underweight. Obesity, compared to normal BMI, was associated with less frequent remission using SDAI (adjusted HR 0.80 [95% CI 0.70-0.92]) and CDAI (adjusted HR 0.77 [0.68-0.87]). As continuous variable, increased BMI was associated with less frequent SDAI (P = 0.001) and CDAI (P = 0.001) defined remission. No heterogeneity in identified associations was observed between studies (P = 0.08) or treatments (P = 0.22). Obesity was negatively associated with RA disease remission regardless of RA therapy, suggesting that baseline BMI should be considered as a stratification factor in future RA trials.