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ID PMID Title PublicationDate abstract
34286535 [Seroprevalence of Toxoplasma gondii infections among patients with autoimmune diseases]. 2020 Jun 28 OBJECTIVE: To understand the seroprevalence of Toxoplasma gondii infections among patients with autoimmune diseases, so as to provide the scientific evidence for the management of toxoplasmosis in patients with autoimmune diseases. METHODS: A total of 237 patients with definitive diagnosis of autoimmune disease were selected as the study subjects, including 79 cases with systemic lupus erythematosus, 71 cases with rheumatoid arthritis and 87 cases with inflammatory bowel disease, while 237 healthy volunteers served as controls. The serum anti-T. gondii IgG antibody was detected using enzyme-linked immunosorbent assay (ELISA) in patients with autoimmune diseases and healthy controls, and the detection of serum IgG antibody against T. gondii was compared between the autoimmune disease patients and healthy controls. RESULTS: The seroprevalence of serum IgG antibody against T. gondii was significantly greater in patients with autoimmune diseases than in healthy controls (29.96% vs. 4.22%; χ(2) = 55.41, P < 0.01), and the seroprevalence of T. gondii infection was all significantly higher in patients with systemic lupus erythematosus (31.65%), rheumatoid arthritis (23.94%) and inflammatory bowel disease (33.33%) than in healthy controls (χ(2) = 45.25, 26.58 and 50.95; all P values < 0.01). CONCLUSIONS: The seroprevalence of anti-T. gondii IgG antibody is significantly higher in patients with autoimmune diseases than in healthy controls, and T. gondii infection may be a potential risk factor for the development of systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel disease.
33104946 Impact of clinical and psychological factors associated with depression in patients with r 2021 May OBJECTIVE: To investigate the prevalence of depressive symptoms and its association with clinical and psychological factors in patients with rheumatoid arthritis (RA) in Germany and in Brazil. METHOD: A convenience sample of 267 RA patients, 176 from Germany (age 62.4 ± 12.3 years) and 91 from Brazil (age 56.3 ± 12.6 years), was used in this cross-sectional study. The following questionnaires were used: Beck Depression Inventory (BDI), painDETECT test, Perceived Stress Questionnaire, fatigue questionnaire (FACIT), Health Assessment Questionnaire Disability Index (HAQ-DI), and the SF-36 questionnaires (Short-Form 36 Health Survey). Disease activity score (DAS 28-CRP) and visual analogue scale (VAS) for pain were also evaluated. Statistical analysis is based on comparison of means and proportions. Statistical significance for non-normal data was evaluated by non-parametrical tests. RESULTS: Depressive symptoms were more prevalent in the Brazilian sample (44% vs 22.9%, p = 0.025). Compared to German patients, the Brazilian ones also experienced more pain (current pain status on VAS: 4.67 ± 3.4 vs 3.67 ± 2.31 respectively, p < 0.01), were physically more limited (1.89 ± 1.85 vs 1.01 ± 0.75, p = 0.012), and had higher C-reactive protein levels (7.78 ± 18.3 vs 5.82 ± 10.45, p = 0.028). Despite receiving a more intensive treatment, German patients presented similar disease activity when compared to Brazilian patients (DAS28-CRP: Brazil 3.4 ± 1.5 vs Germany 3.3 ± 1.3, p = 0.307). CONCLUSION: Depressive symptoms are frequent in RA patients from different countries and interact with psychological disorders and the experience of pain. They contribute negatively to their well-being suggesting the need for psychoeducational strategies. Key Points • New psychoeducational strategies for RA management.• Higher inflammation marker in rheumatoid arthritis patients is associated with depression.• Medical treatment in RA influences depressive symptoms.• Depressive symptoms are dependent on population group.• High disease activity is related to depression.
32890964 Study on the pharmacodynamics and metabolomics of five medicinal species in Atractylodes D 2020 Nov Atractylodes DC. mainly includes Atractylodis Rhizoma and Atractylodis macrocephalae Rhizoma. According to Chinese Pharmacopoeia, Atractylodis Rhizoma is the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis), while Atractylodis macrocephalae Rhizoma is the rhizome of Atractylodes macrocephala Koidz. (A. macrocephala). Although Atractylodes japonica Koidz. ex Kitam. (A. japonica) and Atractylodes coreana (Nakai) Kitam. (A. coreana) are not included in the Pharmacopoeia, they are often used as Atractylodis Rhizoma in northern China. But in Japan, A. japonica is used as Atractylodis macrocephalae Rhizoma. In order to compare the efficacy of A. japonica and A. coreana with that of Atractylodis Rhizoma and Atractylodis macrocephalae Rhizomain in Pharmacopoeia, this paper studies the anti rheumatism of the five medicinal species in Atractylodes DC., and provides the basis for the rational application of A. japonica and A. coreana. With this purpose, the rheumatoid model of rats was established by Freund's complete adjuvant. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF - α), arthritis factor (RF), anti cyclic citrullinated peptide (anti-CCP), interleukin-1β (IL-1β), Nuclear factor-κB (NF - κB), interleukin-10 (IL-10) and Prostaglandin E2 (PGE2) in rats of each group. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to analyze the plasma of each group. After that, multivariate statistical analysis method was used to analyze the data. The results showed that the five medicinal species in Atractylodes DC. can reduce the levels of IL-6, IL-1 β, PGE2 and NF - κB in the plasma of rheumatoid arthritis (RA) rats in varying degrees, among which the regulation of A. macrocephala is relatively weak. A. chinensis, A. lancea, A. coreana and A. japonica can significantly reduce the content of TNF - α, in which A. japonica and A. lancea have better and similar regulatory effects. A. chinensis and A. coreana can significantly reduce the content of RF in arthritis rats. A. coreana, A. lancea and A. japonica can significantly reduce the anti-CCP level, that is, the regulatory effect of A. coreana and A. chinensis is similar. The metabolic disorder of 11-deoxycortisol, taurocholate and other small molecules in the body of rats with RA directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis, leading to the decline of immune function and other symptoms. Most of the metabolic pathways tend to be normal after oral administration of five medicinal species in Atractylodes DC. Among them, the regulating effect of A. coreana and A. chinensis is similar, while that of A. japonica and A. lancea are similar. A. macrocephala had little effect of intervention.
32622695 Comprehensive arginine metabolomics and peripheral vasodilatory capacity in rheumatoid art 2020 Sep BACKGROUND: The relationship between plasma arginine metabolites influencing vascular homeostasis and peripheral vasodilatory capacity in rheumatoid arthritis (RA) patients is not known. METHODS: l-arginine (Arg), monomethyl-l-arginine (MMA), l-homoarginine (hArg), asymmetric dimethyl-l-arginine (ADMA), symmetric dimethyl-l-arginine, and l-citrulline (Cit) were measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) in 164 RA patients and 100 age- and sex-matched healthy controls without previous cardiovascular events. Log-transformed reactive hyperemia index (Ln-RHI) evaluated by flow-mediated pulse amplitude tonometry (PAT, EndoPAT2000 device) was assessed as surrogate measure of peripheral vasodilatory capacity in RA patients. Ln-RHI values <0.51 indicated peripheral endothelial dysfunction (ED). The relationship between plasma arginine metabolite concentrations, RA descriptors and peripheral vasodilatory capacity was evaluated by bivariate correlation and regression analyses. RESULTS: Plasma ADMA concentrations were significantly higher, and plasma hArg concentrations significantly lower, in RA patients than in controls (0.53 ± 0.09 vs 0.465 ± 0.07 μmol/L and 1.50 ± 0.60 vs 1.924 ± 0.78 μmol/L, respectively; p < 0.001 for both comparisons). Bivariate correlation analysis demonstrated no significant correlation between arginine metabolites and disease descriptors. In regression analysis in RA patients, higher plasma ADMA concentrations were independently associated with presence of ED [OR(95% CI) = 77.3(1.478-4050.005), p = 0.031] and lower Ln-RHI [B coefficient(95% CI) = -0.57(-1.09 to -0.05), p = 0.032]. CONCLUSIONS: ADMA was significantly, albeit weakly, associated with impaired microcirculatory vasodilatory capacity and peripheral endothelial dysfunction in RA. This suggests an important pathophysiological role of this metabolite in the vascular alterations observed in this patient group.
32241795 Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes 2020 May OBJECTIVES: To evaluate the cost-effectiveness of treat-to-target strategies among recently diagnosed patients with rheumatoid arthritis (RA) using methotrexate (MTX) and a step-down glucocorticoid (GC) scheme (COBRA Slim) compared with (1) this combination with either sulphasalazine (COBRA Classic) or leflunomide (COBRA Avant-Garde) in high-risk patients and (2) MTX without GCs (Tight-Step-Up, TSU) in low-risk patients. METHODS: The incremental cost-utility was calculated from a healthcare perspective in the intention-to-treat population (n=379) of the 2-year open-label pragmatic randomised controlled Care in early RA trial. Healthcare costs were collected prospectively through electronic trial records. Quality-adjusted life years (QALYs) were estimated using mapping algorithms for EuroQoL-5 Dimension. Multiple imputation was used to handle missing data and bootstrapping to calculate CIs. Robustness was tested with biological disease-modifying antirheumatic drugs at biosimilar prices. RESULTS: In the high-risk group, Classic (∆k€1.464, 95% CI -0.198 to 3.127) and Avant-Garde (∆k€0.636, 95% CI -0.987 to 2.258) were more expensive compared with Slim and QALYs were slightly worse for Classic (∆-0.002, 95% CI -0.086 to 0.082) and Avant-Garde (∆-0.009, 95% CI -0.102 to 0.084). This resulted in the domination of Classic and Avant-Garde by Slim. In the low-risk group, Slim was cheaper (∆k€-0.617, 95% CI -2.799 to 1.566) and QALYs were higher (∆0.141, 95% CI 0.008 to 0.274) compared with TSU, indicating Slim dominated. Results were robust against the price of biosimilars. CONCLUSIONS: The combination of MTX with a GC bridging scheme is less expensive with comparable health utility than more intensive step-down combination strategies or a conventional step-up approach 2 years after initial treatment. TRIAL REGISTRATION NUMBER: NCT01172639.
31998962 Is background methotrexate advantageous in extending TNF inhibitor drug survival in elderl 2020 Sep 1 OBJECTIVE: To evaluate drug survival with monotherapy compared with combination therapy with MTX in RA older adults. METHODS: Patients from the British Society for Rheumatology Biologics Register, a prospective observational cohort, who were biologic naïve and commencing their first TNF inhibitors (TNFi) were included. The cohort was stratified according to age: <75 and ≥75. Cox-proportional hazards models compared the risk of TNFi discontinuation from (i) any-cause, (ii) inefficacy and (iii) adverse events, between patients prescribed TNFi-monotherapy compared with TNFi MTX combination. RESULTS: The analysis included 15 700 patients. Ninety-five percent were <75 years old. Comorbidity burden and disease activity were higher in the ≥75 cohort. Fifty-two percent of patients discontinued TNFi therapy during the follow-up period. Persistence with therapy was higher in the <75 cohort. Patients receiving TNFi monotherapy were more likely to discontinue compared with patients receiving concomitant MTX [hazard rate 1.12 (1.06-1.18) P <0.001]. This finding only held true in patients <75 [hazard rate (HR) 1.11 (1.05-1.17) vs ≥75 [HR 1.13 (0.90-1.41)]. Examining TNFi discontinuation by cause revealed patients ≥75 receiving TNFi monotherapy were less likely to discontinue TNFi due to inefficacy [HR 0.66 (0.43-0.99) P=0.04] and more likely to discontinue therapy from adverse events [HR 1.41(1.02-1.96) P =0.04]. These results were supported by the multivariate adjustment in complete case and imputed analyses. CONCLUSION: TNFi monotherapy is associated with increased treatment failure. In older adults, the disadvantage of TNFi monotherapy on drug survival is no longer seen. Patients ≥75 have fewer discontinuations due to inefficacy than adverse events compared with younger patients. This likely reflects greater disposition to toxicity but perhaps also a decline in immunogenicity associated with immunosenescence.
33337992 Effectiveness and safety of baricitinib in rheumatoid arthritis: a monocentric, longitudin 2021 May OBJECTIVES: Baricitinib is a Janus-kinase (JAK) 1/2 inhibitor, approved for the treatment of moderate-to-severe rheumatoid arthritis (RA) patients with inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We report the first real-life experience with baricitinib in a monocentric cohort of unselected RA patients. METHODS: We enrolled consecutive RA patients starting baricitinib. At baseline and after 4, 12, 24 and 48 weeks we assessed the disease activity by composite indices (SDAI, CDAI and DAS28CRP) and ultrasonography, and we recorded any adverse events. The primary endpoint was the percentage of patients achieving SDAI remission at week 4. RESULTS: We enrolled 59 patients [(F:M = 50:9, median age 58.1 years (IQR 12.8), median disease duration 144 (IQR 150) months] treated with baricitinib in combination with a csDMARD (52.5%) or monotherapy (47.5%) for a median follow-up of 24 weeks (IQR 36). The 12-month drug retention rate was 74%. At weeks 4, 12, 24 and 48 we observed a significant reduction of DAS28, CDAI and SDAI, global health and pain (p<0.001 for all). After 4 weeks of treatment, 12% of patients achieved SDAI remission. Concomitant csDMARDs, previous biological DMARDs, gender, seropositivity and BMI did not affect the efficacy of baricitinib. Baricitinib allowed a significant reduction in prednisone dose after 12 and 24 weeks and a rapid and sustained ultrasound improvement. No serious adverse events, serious infections or cardiovascular events were recorded. CONCLUSIONS: Our study confirms the efficacy and safety profile and rapid onset of the effect of baricitinib in RA patients in a real-life setting.
32909672 Diagnostic accuracy of 14-3-3 η protein in rheumatoid arthritis: A meta-analysis. 2020 Nov AIM: To evaluate the overall diagnostic performance of 14-3-3 η protein in patients with rheumatoid arthritis (RA). METHODS: PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published in English before 20 February 2020 were included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of 14-3-3 η protein for RA was conducted by using a random effects model. Subgroup analysis was used to explore the sources of heterogeneity. Deeks' funnel plot asymmetry test was used to evaluate for the presence of publication bias. RESULTS: A total of 13 studies (1554 positive and 1934 negative participants) were included. The pooled sensitivity and specificity were 0.73 (95% CI 0.71-0.75) and 0.88 (95% CI 0.87-0.90), respectively. The pooled positive/negative likelihood were 5.98 (95% CI 4.39-8.14) and 0.28 (95% CI 0.21-0.37), respectively. In addition, the pooled diagnostic odds ratio was 23.48 (95% CI 13.76-40.08) and the area under curve was 0.9245. The results of subgroup analysis indicated that ethnicity and control group might be the source of heterogeneity. The results of sensitivity analysis were stable. No significant publication bias was found. CONCLUSIONS: The current evidence indicated that 14-3-3 η protein has moderate accuracy for the diagnosis of RA.
33213411 Case report: a man with untreated rheumatoid arthritis, cryoglobulinemic vasculitis, membr 2020 Nov 19 BACKGROUND: Glomerular involvement in rheumatoid arthritis has been known to be associated with treatment side effects from medications and secondary amyloidosis. However, limited basic science and clinical studies have been performed to address the potential disease specific immune-mediated mechanisms causing secondary glomerular pathology, its various types of presentation, and the potential treatments. CASE PRESENTATION: A 41-year-old man with chronic active rheumatoid arthritis presented with nephrotic syndrome and was found to have membranous nephropathy with eosinophilic intracapillary thrombi on renal biopsy. Proteinuria persisted despite complete withdrawal from non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs). Throughout the disease course, he developed cryoglobulinemic vasculitis and pulmonary sarcoidosis, both of which achieved clinical resolution with glucocorticoids. However, only partial improvement was observed in proteinuria with treatment of steroids and Rituximab. CONCLUSION: Our case presented a unique and complicated clinical phenotype of active rheumatoid arthritis, with clinical features of cryoglobulinemic vasculitis, histopathologic features of membranous and cryoglobulinemic nephropathy in the absence of DMARDs use, as well as pulmonary sarcoidosis. We speculate that there is a wider spectrum of glomerular disease in patients with untreated rheumatoid arthritis. In addition, the potential association between rheumatoid arthritis and cryoglobulinemic vasculitis should probably be revisited and requires further studies to elucidate the underlying mechanisms and treatment options.
29873569 The role of self-efficacy in pain intensity, function, psychological factors, health behav 2020 Jan Objective: The aim of this study was to systematically review and critically appraise the role of self-efficacy in pain intensity, function, psychological factors, health behaviors, and quality of life in people with rheumatoid arthritis, based on the analyses of longitudinal studies. Methods: An electronic search of PubMed, AMED, CINAHL, PsycINFO, and PubPsych was carried out from inception to July 2017. Study selection was based on longitudinal studies which have explored the role of self-efficacy in rheumatoid arthritis. The Newcastle-Ottawa Scale adapted version was used to evaluate the risk of bias, whereas the Grading of Recommendations Assessment, Development and Evaluation evaluated the quality of the evidence per outcome. Results: A total of 11 articles met the inclusion criteria. Our results suggest an association between higher self-efficacy and greater goal achievement, positive affect, acceptance of illness, problem-solving coping, physical function, physical activity participation, and quality of life. Inversely, there was also an association between higher self-efficacy and lower pain intensity, depressive symptoms, and anxiety. Conclusions: The findings of this systematic review suggest that self-efficacy might have a positive effect on the prognosis of this condition, although further longitudinal studies are needed.
32979041 Sarcopenia in rheumatoid arthritis: Is it a common manifestation? 2020 Dec OBJECTIVE: To evaluate the presence of sarcopenia in patients with rheumatoid arthritis (RA). METHOD: This cross-sectional study included 100 patients with RA and 100 gender-matched healthy individuals. Sarcopenia was assessed by performing tests evaluating muscle strength, muscle mass, and physical performance, using the criteria determined by The European Working Group on Sarcopenia. Sarcopenia is defined as a decrease in muscle strength and muscle mass. On the other hand, presarcopenia is defined as a decrease in muscle strength with a normal muscle mass. RESULTS: The participants comprised of 70 females and 30 males. The frequency of presarcopenia was 35% in the RA group and 9% in the control group (P < .001). Results of handgrip and gait speed tests were lower in the RA group than in the healthy control group (P = .002 and P < .001, respectively). Presarcopenia was seen at higher rates among female and older patients, and patients with longer disease duration. Disease activity scores were higher in patients with presarcopenia than in patients without sarcopenia (P < .05). In multivariate regression analysis for presarcopenia; a statistically significant association was found between handgrip test results and age, gender, and disease activity (P < .001, R(2)  = .62). CONCLUSIONS: Longer disease duration and higher disease activity may provoke the development of sarcopenia due to chronic inflammation in patients with RA. Physicians should be aware of the development of sarcopenia during the course of disease and take into account the preservative and preventive methods against sarcopenia by encouraging them about exercise along with controlling disease activity.
32428250 EBV and CMV viral load in rheumatoid arthritis and their role in associated Sjögren's syn 2020 Aug INTRODUCTION: The role of viral infections in the pathogenesis of autoimmune diseases has long been suggested, but little evidence is available. OBJECTIVE: This study aimed to evaluate an association between EBV and CMV and the presence of rheumatoid arthritis and its association with Sjögren's Syndrome. PATIENTS AND METHOD: A case-control study was performed with 227 patients divided in RA (n = 99), RA/SS (n = 20), and C (n = 128). Resting salivary flow rate and Schirmer's test were performed; minor salivary gland biopsy was indicated in the case of suspected Sjögren's syndrome. CMV and EBV viral loads were quantified in peripheral blood, and their presence in glandular tissue samples was evaluated by in situ hybridization (EBV) and immunohistochemistry (CMV). RESULTS: EBV was more frequent in RA and RA/SS than in C (P < .000007). No correlation with clinical markers (P > .05) or between RA and RA/SS was found (P > .05). A higher number of EBV/DNA copies were found in RA (158.52 copies/μL) and RA/SS (99.24 copies/μL) (P = .739). EBV/DNA was associated with the Schirmer test (P = .0231). CMV was detected in one patient of the RA group. None of the viruses were detected in biopsies of minor salivary glands. CONCLUSIONS: Detection of EBV/DNA in peripheral blood was associated with RA regardless of the presence of SS.
33285551 Associations between Polymorphisms in the IL-1 Gene and the Risk of Rheumatoid Arthritis a 2021 BACKGROUND: Previous studies on polymorphisms in interleukin-1 (IL-1) and the risk of rheumatoid arthritis (RA)/systemic lupus erythematosus (SLE) yielded inconsistent results. OBJECTIVES: The authors performed this meta-analysis to more robustly evaluate associations between polymorphisms in the IL-1 gene and the risk of RA/SLE. METHODS: MEDLINE, Embase, Web of Science, Wanfang, VIP, and CNKI were systematically searched for eligible studies, and 34 relevant studies were finally selected to be eligible for inclusion. RESULTS: We found that IL-1A +4845G/T polymorphism was significantly associated with the risk of RA in the overall population (dominant comparison: p = 0.02; overdominant comparison: p = 0.05; allele comparison: p = 0.04), whereas IL-1B +3954C/T polymorphism was significantly associated with the risk of RA in the overall population (overdominant comparison: p = 0.03; allele comparison: p = 0.01) and Asians (recessive comparison: p = 0.007; allele comparison: p = 0.002). In addition, we found that IL-1A -889C/T polymorphism was significantly associated with the risk of SLE in Caucasians (allele comparison: p = 0.04), IL-1B -31T/C polymorphism was significantly associated with the risk of SLE in the overall population (recessive comparison: p = 0.04), and IL-1B -511C/T polymorphism was significantly associated with the risk of SLE in Asians (recessive comparison: p = 0.01; allele comparison: p = 0.03). CONCLUSIONS: This meta-analysis suggests that IL-1A +4845G/T and IL-1B +3954C/T polymorphisms may influence the risk of RA, whereas IL-1A -889C/T, IL-1B -31T/C, and IL-1B -511C/T polymorphisms may influence the risk of SLE.
31997083 Disease activity-based management of rheumatoid arthritis in Dutch daily clinical practice 2020 Apr To re-evaluate the adherence to clinical practice guidelines recommended disease activity-based management of rheumatoid arthritis (RA) in daily clinical practice, among Dutch rheumatologists in the past decade. In 2007, disease activity was measured in only 16% of outpatient visits. All rheumatologists that participated in the 2007 study were invited to re-enter our study in 2016/2017. If necessary, data were supplemented with data from other rheumatologists. For all 26 rheumatologists who agreed to participate in our study, data were collected from 30 consecutive patients that visited the outpatient clinic. Per patient, data from four consecutive rheumatologist outpatient visits were collected. Since 2007, disease activity was measured more frequently in Dutch daily clinical practice, increasing from 16 to 79% of visits (2440/3081 visits). In addition, intensification of medication based on disease activity scores increased from 33 to 50% of visits (260/525 visits). DAS/DAS28 was the most frequently used disease activity measure (1596/2440 visits). There was a wide variation among rheumatologists in measuring disease activity and intensification of medication, 20-100% and 0-75% respectively. Over the past years, there has been a large improvement in disease activity assessment in daily clinical practice. Disease activity-based medication intensifications, also called tight control or treat to target, increased to a lesser extent. Large variation between different rheumatologists and clinics indicates that there is still room for improvement. Key Points • Following guideline dissemination disease activity is assessed more frequently (79%). • There is large variation between rheumatologists, indicating room for improvement. • Finding factors that explain variation is necessary to improve tight control in daily practice.
32484820 Hypermethylation of the miR-155 gene in the whole blood and decreased plasma level of miR- 2020 OBJECTIVES: miR-155 plays a critical role in the inflammatory process and in diseases such as rheumatoid arthritis (RA). miR155 gene expression is regulated by its gene promoter region CpG island methylation. Previous studies have shown inconsistent changes in circulating levels of mir-155 in RA patients. The aims of our study were to evaluate miR-155 levels in plasma, to investigate its gene methylation level, and to correlate these levels with RA disease activity. METHODS: One hundred and twenty-five patients with RA, and 30 age and sex-matched healthy controls (HC) were enrolled. Whole blood and plasma samples were collected and stored at -80°C until analysis. DAS28 score at the time of the blood draw was used to assess RA disease activity. The methylation status of miR-155 host gene was determined in whole blood by quantitative real-time methylation-specific PCR (qPCR). miR-155 expression levels were evaluated by quantitative reverse transcription PCR. RESULTS: We found significantly lower circulating miR155 levels in RA patients compared to HC. Interestingly, the miR-155 gene methylation level was significantly higher in RA patients than in HC. miR-155 levels did not correlate with ACPA or RF positivity or disease activity. CONCLUSIONS: We show here higher miR-155 methylation in whole blood and lower plasma miR155 expression in RA patients in comparison to HC. The evaluation of miR-155 host gene methylation status or miR155 plasma level might be a potentially useful marker in RA determination.
32002761 No evidence of abnormal metabolic or inflammatory activity in the brains of patients with 2020 Jun INTRODUCTION/OBJECTIVES: Many individuals with rheumatoid arthritis (RA) report persistent fatigue even after management of peripheral disease activity. This study used whole-brain magnetic resonance spectroscopic imaging (MRSI) to investigate whether abnormal inflammatory activity in the central nervous system may be associated with such symptoms. We hypothesized that RA patients would show higher brain choline (CHO), myo-inositol (MI), and lactate (LAC), and higher brain temperature than healthy controls. We further hypothesized that the metabolite levels would be positively correlated with self-reported fatigue. METHOD: Thirteen women with RA provided fatigue severity ratings and underwent whole-brain MRSI and a joint examination. Thirteen healthy controls (HC) provided comparison imaging and fatigue data. CHO, MI, LAC, and brain temperature in 47 brain regions were contrasted between groups using independent-samples t tests. Significant differences were determined using a false discovery rate (FDR)-adjusted p value threshold of ≤ 0.0023. Secondary analyses obtained correlations between imaging and clinical outcomes in the RA group. RESULTS: No brain metabolic differences were identified between the groups. In the RA group, fatigue severity was positively correlated with CHO in several brain regions-most strongly the right frontal lobe (r(s) = 0.823, p < 0.001). MI was similarly correlated with fatigue, particularly in the right calcarine fissure (r(s) = 0.829, p < 0.001). CHO in several regions was positively correlated with joint swelling and tenderness. CONCLUSIONS: We conclude that abnormal brain metabolites are not a common feature of RA, but may been seen in patients with persistent fatigue or disease activity after conventional treatment.Key Points• Whole-brain magnetic resonance spectroscopy revealed no metabolic abnormalities in the brain in patients with rheumatoid arthritis.• Brain choline levels were correlated with fatigue severity reported by RA patients and with peripheral joint swelling and tenderness.• Brain myo-inositol levels were similarly correlated with fatigue severity in RA patients.
32867830 Efficacy, safety and cost-effectiveness of a web-based platform delivering the results of 2020 Aug 31 BACKGROUND: Rheumatoid arthritis (RA) is one of the leading chronic inflammatory rheumatism. First-line therapy with synthetic disease-modifying antirheumatic drugs (sDMARD) is insufficiently effective in 40% of cases and these patients are treated with biotherapies. The increased use of these drugs each year is becoming a public health issue with considerable economic burden. This cost is 20 times higher than that of sDMARD. However, among patients treated with biotherapies, clinical practice shows that about one third will not respond to the selected drug. In nonresponse cases, practitioners currently have no choice but to perform an empirical switching between different treatments, because no tool capable of predicting the response or nonresponse to these molecules is currently available. METHODS: The study is a prospective, phase III, controlled, multicenter, and randomized, single-blind (patient) clinical trial, including RA patients with a previous failure to anti-TNF therapies. The main objective is the analysis of the clinical and pharmacoeconomic impact after 6 months of treatment. Intervention arm: prescription of biotherapy (rituximab, adalimumab, abatacept) using SinnoTest® software, a prediction software based on proteomic biomarkers. Control arm: prescription of biotherapy based on current practice, without the SinnoTest® software (any biotherapy). In addition, a substudy will be carried out within this trial to generate a biobank and further analyze the proteomic profile of the patients and their modification throughout the study. DISCUSSION: This clinical trial study will be the first validation study of a biotherapy response prediction software, bringing personalized medicine into the management of RA. We expect that the findings from this study will bring several benefits for the patient and the Health Care System. TRIAL REGISTRATION: ClincalTrials.gov NCT04147026 . Registered on 31 October, 2019.
31854453 Rheumatoid arthritis research in the 21st century: Limitations of traditional models, new 2020 Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease characterized by progressive bone and cartilage destruction, functional impairment, and long-term disability. Although RA has been described in the medical lit­erature for over two hundred years, its etiology and pathophysiology are insufficiently understood. The current treatment of RA is mainly empirical or based on drugs that interfere with generic steps of the immune response, with limited efficacy and/or significant side effects. Much of RA research has been traditionally based on animals and simplistic in vitro models, which have been shown to poorly recapitulate human RA etiopathogenesis and drug responses. A revolution in science and technology has produced a new generation of more relevant and predictive tools. These tools, which include patient-derived cells, innovative 3D cell culture systems, computational analyses and models, together with omics and large-scale epidemiological studies represent novel and exciting approaches to enhance and forward RA research in a human biology-based perspective. After considering some pitfalls and flaws of traditional models, in this review we discuss novel tools applicable to design human-oriented RA research, while fostering the need for a more holistic and pre­ventative approach to the disease. Our goal is to stimulate discussion, both at scientific and public level, on the need to explore new avenues in RA research and to support a paradigm-shift from animal-based towards human biology-based systems to better understand human pathophysiology and to develop more effective targeted therapies for personalized treatment and prevention.
32755722 Time to initiation of biologic disease-modifying antirheumatic drugs in the French cohort 2021 Jan OBJECTIVE: To assess the time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) in ESPOIR, the French cohort of patients with rheumatoid arthritis (RA), and factors associated with the timing of bDMARD initiation. METHODS: In total, 658 patients with early RA satisfying the 2010 ACR/EULAR criteria were included between 2003 and 2005 and followed annually for 10 years (end of follow up: 2013-2015). The timing of bDMARD introduction and predictors of use were analysed by the Kaplan-Meier method based on Cox proportional-hazard models. RESULTS: Overall, 178 patients (31.0%, 95% confidence interval [27.0-34.7]) initiated a bDMARD during the 10-year follow-up, with a mean delay of 43.6 months. The penetration rate was higher during the first 2 years of follow-up (6% between the first and second year, approximately 3.3% each year between the second and seventh year, and<2.0% after the eighth year). The first-used bDMARD was etanercept for 72 patients and adalimumab for 71. On multivariate analysis, Disease Activity Score in 28 joints, radiologic progression and positivity for anti-citrullinated protein antibodies were significantly associated with rapid initiation of a bDMARD (P<0.0001), whereas older age at first joint pain was inversely associated (P<0.0001). CONCLUSIONS: Although access to bDMARDs is widespread in France, less than one third of patients with early RA in the ESPOIR cohort initiated a bDMARD over the 10-year follow-up. Poor prognostic factors for RA were associated with more rapid initiation, as expected.
32034957 NETs analysed by novel calprotectin-based assays in blood donors and patients with multipl 2020 May Two novel enzyme-linked immunosorbent assays (ELISAs), designed to detect complexes containing DNA, leucocyte calprotectin and S100A12 proteins, were generated for improved specificity and rapid measurement of neutrophil extracellular traps (NETs). The assays were applied on plasma and serum samples from blood donors for establishment of reference values, and from patients with multiple myeloma (MM) or rheumatoid arthritis (RA) in order to examine putatively increased values in the two different inflammatory conditions. Although NETs were hardly detectable in healthy individuals, NET levels were as expected highly and statistically significantly increased in RA patients. The detection of statistically significantly increased NET levels in MM is a novel finding.