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ID PMID Title PublicationDate abstract
34921962 Preclinical evaluation of Zanthoxylum piperitum Benn., traditional muscle pain remedy, for 2022 Mar 25 ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum piperitum has been used as a traditional Asian medicine to treat hypertension, stroke, bruise and muscle pain. It has been known to induce detoxification; affect anti-bacterial, anti-oxidant, and tyrosinase activity; inhibit osteosarcoma proliferation; anti-osteoarthritis inflammation. In this study, we aim to identify the therapeutic effect of Z. piperitum 90% EtOH extract (ZPE-LR) on rheumatoid arthritis. MATERIAL AND METHODS: We investigated the anti-rheumatoid arthritis and -immunomodulatory activities of the ZPE-LR in collagen-induced arthritic (CIA) mice, a rheumatoid arthritis animal model. In order to assess the analgesic effects of ZPE-LR in vivo, acetic acid injection, formaldehyde injection, hot plate model was used. The mechanism for anti-inflammatory activity of ZPE-LR was identified with LPS-stimulated Raw 264.7 cells. RESULTS: Pharmacologically, oral administration of ZPE-LR into CIA mice resulted in a significant and dose-dependent decrease in clinical arthritis score and paw swelling compared to untreated negative control. Pathologic examination showed that ZPE-LR prevented morphological change in cartilage and destruction of phalanges in CIA mice. This protective effect was associated with reduced pain, inflammatory mediators such as NO, TNF-α, IL-1β, and IL-6, as well as COX-2 and iNOS expression. Furthermore, reduction of phosphor-ERK and BDNF indicates a novel rheumatoid arthritis-regulating mechanism by ZPE-LR treatment. CONCLUSIONS: These data suggest that the administration of ZPE-LR remarkably inhibited CIA progression and might be helpful in suppressing inflammation and pain in rheumatoid arthritis.
33438080 Chagas disease reactivation in rheumatologic patients: association with immunosuppressive 2021 Jul Evidence for Chagas disease reactivation (CDR) in rheumatologic patients under rheumatologic treatments (RTs) is scarce. To screen and follow-up patients with rheumatic diseases and concomitant Chagas disease under RT to detect CDR and to describe a possible relationship between CDR and specific RT. An observational, longitudinal, prospective, consecutive study was carried out between 2018 and 2020. Included patients were evaluated during the follow-up for clinical and laboratorial manifestations of CDR. Direct blood parasitological examination (Strout method) and polymerase chain reaction (PCR) were employed to diagnose CDR. The dynamic of anti-T. cruzi-specific antibodies was also assessed by IHA and ELISA (total IgG and Anti-SAPA). Fifty-one patients were included (86% women). Rheumatoid arthritis was the predominant disease (57%). Classic DMARDs (86.3%) and corticosteroids (61%) were the most frequent RT. CDR was developed in 6 patients (11.7%), exhibiting both positive Strout and PCR. Symptomatic reactivation of CD (fever, asthenia, arthralgias, myalgias) occurred in two patients who had previously been diagnosed with it. Regardless of the different RT, all patients who experienced CDR had previously received more than ≥ 20 mg/day of prednisone equivalent. Despite immunosuppression, patients with CDR exhibited increased levels of specific anti-T. cruzi and anti-SAPA antibodies, which decreased after anti-parasitic treatment. CDR is possible in rheumatologic patients, especially after receiving high doses of corticosteroids. Since CDR symptoms may mimic rheumatic disease activity, monitoring of Chagas disease is highly recommended before, during and after immunosuppression. Key Points • Chagas disease reactivation (CDR) in the context of rheumatological treatment was associated to high doses of corticosteroids. • CDR was associated with an increase in anti-T. cruzi antibodies despite the immunosuppressive treatment. • Suspecting and anticipating CDR is mandatory in this patient population to diagnose and treat it.
32855529 Deficiency of β-arrestin2 exacerbates inflammatory arthritis by facilitating plasma cell 2021 May β-arrestin2 (β-arr2) is, a key protein that mediates desensitization and internalization of G protein-coupled receptors and participates in inflammatory and immune responses. Deficiency of β-arr2 has been found to exacerbate collagen antibody-induced arthritis (CAIA) through unclear mechanisms. In this study we tried to elucidate the molecular mechanisms underlying β-arr2 depletion-induced exacerbation of CAIA. CAIA was induced in β-arr2(-/-) and wild-type (WT) mice by injection of collagen antibodies and LPS. The mice were sacrificed on d 13 after the injection, spleen, thymus and left ankle joints were collected for analysis. Arthritis index (AI) was evaluated every day or every 2 days. We showed that β-arr2(-/-) mice with CAIA had a further increase in the percentage of plasma cells in spleen as compared with WT mice with CAIA, which was in accordance with elevated serum IgG1 and IgG2A expression and aggravating clinical performances, pathologic changes in joints and spleen, joint effusion, and joint blood flow. Both LPS stimulation of isolated B lymphocytes in vitro and TNP-LPS challenge in vivo led to significantly higher plasma cell formation and antibodies production in β-arr2(-/-) mice as compared with WT mice. LPS treatment induced membrane distribution of toll-like receptor 4 (TLR4) on B lymphocytes, accordingly promoted the nuclear translocation of NF-κB and the transcription of Blimp1. Immunofluorescence analysis confirmed that more TLR4 colocalized with β-arr2 in B lymphocytes in response to LPS stimulation. Depletion of β-arr2 restrained TLR4 on B lymphocyte membrane after LPS treatment and further enhanced downstream NF-κB signaling leading to additional increment in plasma cell formation. In summary, β-arr2 depletion exacerbates CAIA and further increases plasma cell differentiation and antibody production through inhibiting TLR4 endocytosis and aggravating NF-κB signaling.
33870656 Nanomedicine Strategies for Anti-Inflammatory Treatment of Noninfectious Arthritis. 2021 Jun Noninfectious arthritis (NIA) comprises a class of chronic and progressive inflammatory disorders that require early-stage management to prevent disease progression. The most common forms include osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and gouty arthritis. Current treatments involve nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs and glucocorticoids to alleviate clinical symptoms, although regular use of these can result in a high risk of chronic kidney disease and heart failure, as well as severe adverse gastrointestinal effects. Nanomedicine offers unique opportunities to address these challenges and improve therapeutic efficacy due to its ability to deliver therapeutics locally in a sustained manner, thus extending the half-life, improving bioavailability, and reducing the side effects of these agents. This review includes a comprehensive analysis of the mechanisms of various treatment options for NIA and highlights recent progress and emerging strategies in treating NIA with nanomedicine platforms, particularly related to long-term biosafety and nonspecific targeting in designing nanomedicine delivery systems.
33419871 Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheum 2021 Jan OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA. METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias. CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.
33404658 Imbalanced MMP-3 and MMP-12 serum levels in systemic lupus erythematosus patients with Jac 2021 Sep 1 OBJECTIVE: Metalloproteinase (MMP)-3 and MMP-12 are proteolytic enzymes especially implicated in joint inflammation. This study aims to evaluate their association with arthritis features and hand MRI abnormalities in patients with SLE. METHODS: Fifty SLE patients, with a mean (s.d.) age of 48.1 (14.6) years were tested for MMP-3 and MMP-12 serum levels, then further classified according to the presence of X-ray erosions and joint deformities. Eighteen RA patients aged 47.9 (11.8) and 14 healthy people aged 46.0 (11.0) were enrolled as control groups. A subgroup of 28 SLE patients underwent a dominant-hand MRI; the detected changes were classified and semi-quantitatively scored as capsular swelling, synovitis, edematous or proliferative tenosynovitis, bone oedema, bone erosions. Statistical analysis was performed using multiple regression models. RESULTS: MMP-3 were significantly higher in patients with Jaccoud's arthropathy (JA) (22.1 ng/ml, P < 0.05) and independently associated with hsCRP serum levels (B-coeff 0.50; r = 0.30; P < 0.05). MMP-12 serum levels were significantly lower in patients with JA (0.18 ng/ml, P < 0.05) and inversely associated with the prednisone daily dose (B-coeff -0.03; r = -0.44; P < 0.01). Capsular swelling and edematous tenosynovitis, the most prevalent hand MRI changes in patients with JA, associated with higher MMP-3 (B-coeff 0.12; r = 0.66; P < 0.01 and B-coeff 0.08; r = 0.59; P < 0.01, respectively) and lower MMP-12 serum levels (B-coeff -7.4; r = -0.50; P < 0.05 and B-coeff -5.2; r = -0.44; P = 0.05, respectively). CONCLUSION: Imbalanced MMP-3 and MMP-12 serum levels are influenced by inflammation and glucocorticoids in SLE patients and associated with JA and distinctive hand MRI changes.
33526927 Location, location, location: how the tissue microenvironment affects inflammation in RA. 2021 Apr Current treatments for rheumatoid arthritis (RA) do not work well for a large proportion of patients, or at all in some individuals, and cannot cure or prevent this disease. One major obstacle to developing better drugs is a lack of complete understanding of how inflammatory joint disease arises and progresses. Emerging evidence indicates an important role for the tissue microenvironment in the pathogenesis of RA. Each tissue is made up of cells surrounded and supported by a unique extracellular matrix (ECM). These complex molecular networks define tissue architecture and provide environmental signals that programme site-specific cell behaviour. In the synovium, a main site of disease activity in RA, positional and disease stage-specific cellular diversity exist. Improved understanding of the architecture of the synovium from gross anatomy to the single-cell level, in parallel with evidence demonstrating how the synovial ECM is vital for synovial homeostasis and how dysregulated signals from the ECM promote chronic inflammation and tissue destruction in the RA joint, has opened up new ways of thinking about the pathogenesis of RA. These new ideas provide novel therapeutic approaches for patients with difficult-to-treat disease and could also be used in disease prevention.
34446270 Development of a patient-centered core domain set for prospective observational longitudin 2021 Oct OBJECTIVES: To identify patient-centered core domains for prospective longitudinal observational studies (LOS) in rheumatoid arthritis. METHODS: Our working group held a virtual meeting in November 2020 to review data from a literature review and patient qualitative interviews, and to discuss strategies to move forward on domain identification and selection using the OMERACT 2.1 domain selection process. RESULTS: Important candidate domains and subdomains were identified including in the areas of life impact. Consensus was reached on moving forward with a Delphi process. CONCLUSIONS: The meeting provided future directions to identify and select a core set of domains for use in LOS.
34766563 Neutrophil-lymphocyte, platelet-lymphocyte and lymphocyte-monocyte ratios may not be usefu 2021 Nov 12 The associations among the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and lymphocyte-monocyte ratio (LMR) and disease activity in rheumatoid arthritis remains unclear.To evaluate these indicators as potential markers of disease activity in patients with rheumatoid arthritis (RA).This cross-sectional study included 547 adult patients with RA. The patients were divided into two groups according to the disease activity score (DAS) system: remission and disease activity. Differences in the NLR, PLR and LMR of the two groups were assessed. Correlations were analyzed using Spearman analysis, and receiver operating characteristic (ROC) curves were used to identify the sensitivity, specificity, and optimal cutoff values to differentiate active RA patients from inactive RA patients.There was a statistically significant difference in the NLR (4.2 ± 3.2 vs 3.4 ± 2.4, P = .034) and PLR (222.3 ± 136.4 vs 176.9 ± 89.8, P = .006) between the two groups, but not for the LMR (3.0 ± 1.8 vs 3.4 ± 2.4, P = .115). In addition, the DAS28 and traditional inflammatory markers, including ESR and CRP, were weakly positively correlated with the NLR and PLR. Based on the ROC curves, the NLR (sensitivity 31.8%, specificity 77.8%) and PLR (sensitivity 57.3%, specificity 63.9%) were less valuable than the ESR (sensitivity 67.2%, specificity 91.7%) and CRP (sensitivity 76.2%, specificity 91.7%) for differentiating inactive RA patients from active RA patients due to low sensitivity and specificity and combining NLR or PLR also cannot significantly improved the diagnostic value of ESR and CRP.NLR, PLR and LMR may not be an useful independent diagnostic or complementary marker for disease activity in RA patients.
33572002 Total Flavonoids of Bidens pilosa Ameliorates Bone Destruction in Collagen-Induced Arthrit 2021 Jun Rheumatoid arthritis is a chronic autoimmune disease characterized by the infiltration of synovial inflammatory cells and progressive joint destruction. Total flavonoids of Bidens pilosa have been used against inflammation in rheumatoid arthritis, but its role in bone destruction remains to be explored. The aim of this paper was to study whether total flavonoids of B. pilosa relieve the severity of collagen-induced arthritis in rats, particularly whether it regulates the production of proinflammatory cytokines and the receptor activator of nuclear factor-κB/receptor activator of nuclear factor-κB ligand/osteoprotegerin signaling pathway. In this research, a collagen-induced disease model was induced in adult rats by subcutaneous injection of collagen II. Total flavonoids of B. pilosa at different doses (40, 80, and 160 mg/kg/d) were administered intragastrically, while methotrexate (1 mg/kg/w) was injected intraperitoneally as a positive control. Paw swelling, arthritis score, and body weight were assessed and evaluated. The severity of joint damage was determined using X-ray and confirmed by histopathology. The expression levels of receptor activator of nuclear factor-κB ligand, osteoprotegerin, IL-1β, IL-17, and TNF in the serum and tissue were assayed using ELISA and immunohistochemistry. We found that total flavonoids of B. pilosa attenuated collagen-induced arthritis at the macroscopic level, and total flavonoids of B. pilosa-treated rats showed reduced paw swelling, arthritis scores, and X-ray appearance of collagen-induced arthritis in addition to improved histopathological results. These findings were consistent with reduced serum and tissue receptor activator of nuclear factor-κB ligand, TNF, IL-1β, and IL-17 levels but increased osteoprotegerin levels. Our data suggest that total flavonoids of B. pilosa attenuate collagen-induced arthritis by suppressing the receptor activator of nuclear factor-κB ligand/receptor activator of nuclear factor-κB/osteoprotegerin pathway and the subsequent production of proinflammatory cytokines. In addition, total flavonoids of B. pilosa may be a promising therapeutic candidate for the management of rheumatoid arthritis.
33972623 Factors contributing to discrepant estimated glomerular filtration values measured by crea 2021 May 10 This study aimed to clarify the factors underlying the discrepancy that has been noted between estimated glomerular filtration ratio (eGFR) measured using serum creatinine (Cr) and eGFR using serum cystatin C (CysC) in patients with rheumatoid arthritis (RA) and to identify those patients whose renal function should be evaluated using CysC. We retrospectively evaluated clinical features, disease activity, Steinbrocker radiological staging, and co-morbidities (diabetes mellitus, hypertension, dyslipidemia) in 238 RA patients. eGFR using serum creatinine (eGFR-Cr) and eGFR using serum cystatin C (eGFR-CysC) were calculated using the new Japanese coefficient-modified Modification of Diet in Renal Disease study equation. To clarify the cause(s) of differences of 20% or more between the two eGFRs, we divided our RA patients into Group A (eGFR-Cr/eGFR-CysC ≥ 1.2) and Group B (eGFR-Cr/eGFR-CysC < 1.2), and searched for factors independently related to Group A. Forty-five patients (18.9%) were assigned to Group A, and 193 (81.1%) to Group B. BMI (Odds Ratio [OR] 0.820, 95% confidence interval [CI] 0.675-0.996), Hb (OR 0.633, 95% CI 0.433-0.926), CK (OR 0.773 per 10 units, 95% CI 0.644-0.933), NSAID use (OR 0.099, 95% CI 0.020-0.494), diabetes mellitus (OR 6.024, 95% CI 1.508-24.390) and stage 4 Steinbrocker radiological stage (OR 10.309, 95% CI 2.994-35.714) were identified as independent relevant factors for Group A by a multifactorial analysis. Renal function in RA patients with low BMI, diabetes, anemia and low CK may be overestimated using eGFR-Cr alone, and such patients need to be evaluated using eGFR-CysC.
33719901 Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study 2021 Jul Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.
34236304 Utilization of targeted disease-modifying anti-rheumatic drugs (DMARDs) for managing rheum 2021 Oct OBJECTIVE: To compare trends in the use of targeted disease-modifying anti-rheumatic drugs (DMARDs) for rheumatoid arthritis (RA), between Korea and Australia. MATERIALS AND METHODS: Using sampled claims databases in Korea and Australia (2010 - 2018), we analyzed the trends in the use of individual targeted DMARDs (biologic and targeted synthetic) for RA in both countries. RESULTS: The use of targeted DMARDs for the management of RA showed an increase of over 200 and 300% in Australia and Korea, respectively. The tumor necrosis factor inhibitors (TNFis) etanercept and adalimumab were the most commonly prescribed drugs in 2010 in both countries, with non-TNFi use increasing over the study period. The introduction of tofacitinib in 2015 led to 10 and 15% market share uptake in Korea and Australia, respectively. CONCLUSION: Trends in the use of targeted DMARDs for RA were similar in Korea and Australia, and the use of non-TNFis, including tofacitinib, increased in both countries.
31841259 Association of Low Muscle Density With Deteriorations in Muscle Strength and Physical Func 2021 Mar OBJECTIVE: Rheumatoid arthritis (RA) is associated with low muscle density due to the accumulation of intramuscular fat. The present study was undertaken to identify predictors of changes in muscle density and to determine whether low muscle density predicted changes in strength and physical function. METHODS: Patients with RA, ages 18-70 years, completed whole-body dual-energy x-ray absorptiometry and peripheral quantitative computed tomography to quantify lean and fat mass indices and muscle density. Dynamometry was used to measure strength at the hand, knee, and lower leg. Disability and physical function were measured with the Health Assessment Questionnaire (HAQ) and the Short Physical Performance Battery (SPPB). Assessments were performed at baseline and at follow-up. Regression analyses assessed associations between patient characteristics, muscle density, and deteriorations in strength and function. RESULTS: Muscle density was assessed at baseline in 107 patients with RA. Seventy-nine of these patients (74%) returned for a follow-up assessment at a median follow-up time of 2.71 years (interquartile range 2.35-3.57). Factors associated with declines in muscle density included female sex, higher disease activity, smoking, and lower insulin-like growth factor 1 (IGF-1) levels. Greater muscle density Z score at baseline (per 1 SD) was associated with less worsening per year according to HAQ, SPPB, and 4-meter walk time scores and a lower risk of a clinically important worsening in HAQ score (odds ratio [OR] 1.90 [95% confidence interval (95% CI) 1.06, 3.42]; P = 0.03) and walking speed (OR 2.87 [95% CI 1.05, 7.89]; P = 0.04). CONCLUSION: Worsening of skeletal muscle density occurred in patients with higher disease activity, in smokers, and in those with lower IGF-1. Low muscle density was associated with worsening of physical function. Interventions addressing reductions in muscle quality might prevent functional decline.
33124566 Interleukin-33 promotes proliferation and inhibits apoptosis of fibroblast-like synoviocyt 2021 Jul OBJECTIVES: The aim of our study was to determine the effect of interleukin (IL)-33 on the proliferation, apoptosis, and secretion of inflammatory cytokines by fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) and to investigate the underlying mechanisms. METHODS: Cultured RA FLSs and osteoarthritis (OA) FLSs were cocultured with different concentrations of IL-33. TUNEL assay and flow cytometry were used to detect apoptosis. Western blotting and Real-time (RT)-PCR were used to detect the expression levels of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), while the Cell Counting Kit-8 was used to determine cell proliferation in each cocultured group. Enzyme-linked immunosorbent assay was used to detect the expression levels of tumour necrosis factor (TNF)-α and IL-6 in the supernatant from each cell culture. Western blot analysis was used to determine the phosphorylated expression levels of the nuclear factor-kappa light chain enhancer of the activated B cells (NF-κB) pathway in each group. RESULTS: IL-33 inhibited RA FLS apoptosis, promoted FLS proliferation, increased Bcl-2 protein expression levels, and decreased Bax protein expression levels. It also increased the expression levels of inflammatory cytokines TNF-α and IL-6 and increased the expression levels of P-NF-κ B in FLSs. CONCLUSIONS: IL-33 inhibited apoptosis and promoted proliferation of FLSs; in addition, IL-33 increased the serum levels of inflammatory cytokines. The effect of IL-33 on RA FLSs was likely mediated via the NF-κB pathway.
34224029 Identification of differential key biomarkers in the synovial tissue between rheumatoid ar 2021 Dec INTRODUCTION/OBJECTIVES: Rheumatoid arthritis (RA) and osteoarthritis (OA) are two common joint diseases with similar clinical manifestations. Our study aimed to identify differential gene biomarkers in the synovial tissue between RA and OA using bioinformatics analysis and validation. METHOD: GSE36700, GSE1919, GSE12021, GSE55235, GSE55584, and GSE55457 datasets were downloaded from the Gene Expression Omnibus database. A total of 57 RA samples and 46 OA samples were included. The differentially expressed genes (DEGs) were identified. The Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed. Protein-protein interaction (PPI) network of DEGs and the hub genes were constructed and visualized via Search Tool for the Retrieval of Interacting Genes/Proteins, Cytoscape, and R. Selected hub genes were validated via reverse transcription-polymerase chain reaction. RESULTS: A total of 41 DEGs were identified. GO functional enrichment analysis showed that DEGs were enriched in immune response, signal transduction, regulation of immune response for biological process, in plasma membrane and extracellular region for cell component, and antigen binding and serine-type endopeptidase activity for molecular function. KEGG pathway analysis showed that DEGs were enriched in cytokine-cytokine receptor interaction and chemokine signaling pathway. PPI network analysis established 70 nodes and 120 edges and 15 hub genes were identified. The expression of CXCL13, CXCL10, and ADIPOQ was statistically different between RA and OA synovial tissue. CONCLUSION: Differential expression of CXCL13, CXCL10, and ADIPOQ between RA and OA synovial tissue may provide new insights for understanding the RA development and difference between RA and OA. Key Points • Bioinformatics analysis was used to identify the differentially expressed genes in the synovial tissue between rheumatoid arthritis and osteoarthritis. • CXCL13, CXCL10, and ADIPOQ might provide new insight for understanding the differences between RA and OA.
33044725 Accessibility to biologics and its impact on disease activity and quality of life in patie 2021 May OBJECTIVE: Biologics are indicated in rheumatoid arthritis (RA) in case of persistent high disease activity despite conventional disease-modifying anti-rheumatic drugs (cDMARDs) or patients with contraindications to cDMARDs or poor prognostic factors. The purpose of this study was to compare the prescription rates of biologics in Kuwaiti and non-Kuwaiti patients and to assess whether this had an impact on disease activity and quality of life in RA patients. METHODS: Data were extracted from the Kuwait Registry for Rheumatic Diseases. Adult patients who satisfied the ACR classification criteria for RA from four major hospitals in Kuwait were evaluated from February 2013 through May 2018. The treatment agents, disease activity, and quality of life of Kuwaiti patients were compared with non-Kuwaiti patients. RESULTS: A total of 1651 RA patients were included; 806 (48.8%) were Kuwaiti patients. Among Kuwaiti patients, 62.5% were on biologic drugs in comparison with 14% of non-Kuwaiti patients. In comparison with non-Kuwaiti patients, Kuwaiti patients had significantly lower numbers of swollen joints (p < 0.001) and disease activity score-28 scores (p = 0.02) and less steroid use (p < 0.001) yet a significantly higher health assessment questionnaire-disability index (p < 0.001). Regression analysis showed that DAS-28 scores were significantly associated with the treatment type (p < 0.001) and that nationality was significantly predictive of the treatment type (p < 0.001). CONCLUSION: In the setting of easy accessibility to treatment for Kuwaiti patients, biologics were prescribed by rheumatologists at a higher rate than for non-Kuwaitis. This may explain the lower disease activity and the lower rate of steroid use in Kuwaiti patients than non-Kuwaitis. KEY POINTS: • Significant discrepancies in the rates of prescribing biologic therapies between KP and NKP in Kuwait were observed. • Several treatment outcomes were significantly better in the KP group than in the NKP group even after adjustment of confounding factors. • The poor access to biologic therapies was suggested to limit the effectiveness of RA treatments in the NKP group.
34341435 Plasma expression of microRNA-425-5p and microRNA-451a as biomarkers of cardiovascular dis 2021 Aug 2 To validate in a cohort of 214 rheumatoid arthritis patients a panel of 10 plasmatic microRNAs, which we previously identified and that can facilitate earlier diagnosis of cardiovascular disease in rheumatoid arthritis patients. We identified 10 plasma miRs that were downregulated in male rheumatoid arthritis patients and in patients with acute myocardial infarction compared to controls suggesting that these microRNAs could be epigenetic biomarkers for cardiovascular disease in rheumatoid arthritis patients. Six of those microRNAs were validated in independent plasma samples from 214 rheumatoid arthritis patients and levels of expression were associated with surrogate markers of cardiovascular disease (carotid intima-media thickness, plaque formation, pulse wave velocity and distensibility) and with prior cardiovascular disease. Multivariate analyses adjusted for traditional confounders and treatments showed that decreased expression of microRNA-425-5p in men and decreased expression of microRNA-451 in women were significantly associated with increased (β = 0.072; p = 0.017) and decreased carotid intima-media thickness (β = -0.05; p = 0.013), respectively. MicroRNA-425-5p and microRNA-451 also increased the accuracy to discriminate patients with pathological carotid intima-media thickness by 1.8% (p = 0.036) in men and 3.5% (p = 0.027) in women, respectively. In addition, microRNA-425-5p increased the accuracy to discriminate male patients with prior cardiovascular disease by 3% (p = 0.008). Additionally, decreased expression of microRNA-451 was significantly associated with decreased pulse wave velocity (β = -0.72; p = 0.035) in overall rheumatoid arthritis population. Distensibility showed no significant association with expression levels of the microRNAs studied. We provide evidence of a possible role of microRNA-425-5p and microRNA-451 as useful epigenetic biomarkers to assess cardiovascular disease risk in patients with rheumatoid arthritis.
34139521 Association of first, second, and third-line bDMARDs and tsDMARD with drug survival among 2021 Aug OBJECTIVES: To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients. METHODS: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date. RESULTS: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69-0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25-0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19-0.63) was associated with lower drug failure risk compared to third TNFi users. CONCLUSION: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.
33336324 What Are the Preferences of Patients With Rheumatoid Arthritis for Treatment Modification? 2021 Sep OBJECTIVES: Optimal care of rheumatoid arthritis (RA) patients entails regular assessment of disease activity and appropriate adjustment of disease-modifying antirheumatic drugs (DMARDs) until a predefined treatment goal is achieved. This raises questions about the approach to treatment decision making among RA patients and their preference for associated treatment changes. We aimed to systematically identify and synthesize the available evidence of RA patients' preferences regarding DMARD modification with an emphasis on escalating, tapering, stopping, or switching of DMARDs. METHODS: A scoping review was undertaken to gauge the breadth of evidence from the range of studies relating to RA patients' preferences for DMARD modification. Pertinent databases were searched for relevant studies published between 1988 and 2019. Conventional content analysis was applied to generate themes about how patients perceive changes to their RA treatment. RESULTS: Of the 1730 distinct articles identified, 32 were included for review. Eight studies investigated RA patients' perceptions of switching to other DMARDs, 18 studies reported RA patients' preferences for escalating treatment, and six studies explored the possibility of tapering or stopping of biologic DMARDs. Four overarching themes relating to RA patients' preferences for treatment modification were identified: (i) patient satisfaction, (ii) patients' beliefs, (iii) information needs, and (iv) patient-clinician relationships. CONCLUSION: Uptake of treatment changes in clinical practice can be improved by understanding how RA patients approach the decision to modify their treatment and how this relates to their satisfaction, beliefs, information needs, and relationships with clinicians. Future work is needed to systematically determine the significance of these factors in RA patients' decision-making processes.