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ID PMID Title PublicationDate abstract
32141954 Management issues in rheumatoid arthritis-associated interstitial lung disease. 2020 May PURPOSE OF REVIEW: Summarize recent evidence on the identification and management of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). RECENT FINDINGS: Clinical and subclinical interstitial lung disease (ILD) are frequent extra-articular manifestations of rheumatoid arthritis (RA). Better means of identifying and treating RA-ILD are needed to improve the prognosis, with a median survival of only 3-7 years after diagnosis. Several serum biomarkers are currently being evaluated for their ability to detect RA-ILD. Thorough evaluation and multidisciplinary discussion remains the gold standard for establishing the diagnosis of RA-ILD. Management is challenging with most RA disease-modifying antirheumatic drugs (DMARDs) linked to pneumonitis. Methotrexate is typically avoided in clinically significant ILD, although alternative therapies including leflunomide and biologic DMARDs also carry risks in RA-ILD. Antifibrotics appear to slow the progression of ILD, and a large phase II trial exclusively in RA-ILD is underway. In addition, smoking cessation, pulmonary rehabilitation, oxygen therapy, managing comorbidities, and lung transplantation evaluation are vital to improving patient outcomes in RA-ILD. SUMMARY: With little high-quality evidence to guide the management of RA-ILD, multidisciplinary teams with expertise in RA-ILD are highly valuable for diagnosing and treating RA-ILD. Clinical and translational research in RA-ILD is needed to fill the many evidence gaps.
32385141 Management of Fatigue in Rheumatoid Arthritis. 2020 May Fatigue in rheumatoid arthritis is highly prevalent. It is correlated only weakly with disease activity but more so with pain, mood, personality features, poor sleep, obesity and comorbidities. Fatigue can be measured by many standardised questionnaires and more easily with a Visual Analogue Scale or numeric rating scale. Most patients with RA have some fatigue, and at least one in six have severe fatigue. Chronic pain and depressed mood are also common in RA patients with significant fatigue. It affects function and quality of life and is worse on average in women. Evidence-based treatment for fatigue includes treatment of underlying disease activity (with on average modest improvement of fatigue), exercise programmes and supervised self-management programmes with cognitive-behavioural therapy, mindfulness and reinforcement (such as reminders). The specific programmes for exercise and behavioural interventions are not standardised. Some medications cause fatigue such as methotrexate. More research is needed to understand fatigue and how to treat this common complex symptom in RA that can be the worst symptom for some patients.
32143989 Insights into the treatment of rheumatoid arthritis: A paradigm in medicine. 2020 Jun Insights into rheumatoid arthritis (RA) have slowly evolved over the last century, but with breathtaking speed over the last 2 decades. While only aspirin and parenteral gold were available in early 20th century, the efficacy of sulfasalazine, glucocorticoids and methotrexate was established around its middle. Identification of pathogenetic pathways was slow, and until today the role of T-cells is enigmatic, while it is clear that genetics via the shared epitope and other genes as well as environmental factors including the metagenome play major roles. More clarity evolved on importance of proinflammatory cytokines, especially TNF and IL-6. The activation of osteoclasts, the culprits of bony joint damage, is amplified by the proinflammatory cytokines. The realization of TNF's central role led to the successful introduction of TNF-inhibitors and subsequently also inhibitors of other cytokines and cells as well as signal transduction. In parallel, the evolution of outcomes research has contributed importantly to RA management. At the turn to the 21st century, improvement criteria and continuous indices were created, allowing reliable therapeutic response determination, including definition of endpoints like remission. Also our understanding of the role of disease activity relative to disease pathology has increased, ultimately fostering the treat-to-target concept and recommendations and, thus, optimal outcomes for RA patients as never been seen before. Similar developments are now ultimately being introduced in the field of psoriatic arthritis. Here many of these aspects are reviewed from a very personal perspective of the author in the hopes of further helping parients with chronic forms of arthritis.
32829543 Metabolic Syndrome In Young Rheumatoid Arthritis Patients. 2020 Jul BACKGROUND: Metabolic Syndrome is strongly associated with Rheumatoid Arthritis, which significantly increases cardiovascular complications and hence morbidity and mortality. Treating Metabolic Syndrome decreases cardiovascular related disease flares and deaths. This study evaluates prevalence of metabolic syndrome in young Rheumatoid Arthritis patients. METHODS: This Cross-sectional study was conducted in rheumatology department of a tertiary care hospital in Karachi. All diagnosed cases of rheumatoid arthritis from April to August 2018 were consecutively included. Disease activity of rheumatoid arthritis assessed by Clinical Disease Activity Index (CDAI). Associate determinants of rheumatoid arthritis were measured along with outcome variables. RESULTS: Out of 104 rheumatoid arthritis patients, 34 (32.7%) found to have metabolic syndrome in whom 20 (58.8%) of patients were seropositive. A significant association of metabolic syndrome was found with age (p-value 0.023), BMI (p-value 0.006), waist circumference (p-value 0.002), FBS (p-value <0.001), SBP (p-value <0.001), DBP (p-value <0.001), TG (p-value <0.001), HDL (p-value 0.022), and Methotrexate drug history (p-value 0.030). CONCLUSIONS: We conclude that metabolic syndrome is highly prevalent in young rheumatoid patients with rheumatoid arthritis. Treating Metabolic Syndrome decreases cardiovascular related disease flares and deaths. This young population base study will help out to estimate the exact burden of Metabolic Syndrome to decrease overall morbidity and mortality.
32936111 Rheumatoid arthritis with necrotic lung nodules. 2020 Sep Rheumatoid arthritis is a multisystemic inËœflammatory disease. Lungs are the commonest site of extra-articular involvement. Rheumatoid lung nodules occur infrequently and can undergo necrosis giving rise to necrobiotic lung nodules. Infections, malignancy and granulomatosis with polyangiitis are more common causes of cavitating lung nodules. Presence of rheumatoid factor, history of smoking and use of methotrexate increase the chances of developing rheumatoid lung nodulosis. Histopathological examination of the nodule is essential to make a correct diagnosis. We present a 74-year-old male with long-standing rheumatoid arthritis who had multiple cavitating lung nodules. Biopsy from the lung nodule could not be performed as the patient refused to consent. However, infection, malignancy and granulomatosis with polyangiitis were ruled out on the basis of blood investigations and bronchoscopy. He was empirically treated with a moderate dose of glucocorticoid along with conventional synthetic disease-modifying antirheumatic drugs. After three months of treatment, the lung nodules disappeared completely and his articular symptoms showed marked improvement.
32942096 Drug-resistance in rheumatoid arthritis: the role of p53 gene mutations, ABC family transp 2020 Oct Rheumatoid arthritis (RA) is an autoimmune disease that is associated with chronic inflammation in joints, which contribute to synovial membrane hyperplasia and cartilage damage. Conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate (MTX) and leflunomide (LEF), are the common RA therapy to reduce inflammation and disease progression. Recently, drug-resistance in RA with conventional treatment has become an issue. Mutations in p53 tumor suppressor gene and overexpression of ABCB1/MDR-1/P-gp transporters may contribute to antirheumatic drug-resistance in RA. Biologic DMARDs (bDMARDs) are often prescribed, when conventional DMARDs fail to treat RA, by targeting proinflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. The efficacy of bDMARDs is affected by personal factors, for example, age, smoking, body mass index (BMI), immunogenicity, and genetic polymorphisms. This review highlights the role of p53 gene mutations, ABC family transporters and personal factors in antirheumatic drug-resistance, which may lead to new personalized therapies against RA with an increased drug-sensitivity.
33210179 Efficacy of methotrexate in reducing the risk of bone erosion in patients with rheumatoid 2021 May Even though new drugs for the treatment of rheumatoid arthritis (RA) have been developed, methotrexate (MTX) remains a commonly used drug for RA management. In addition to monitoring disease activity during RA treatment, bone erosion should be closely assessed throughout long-term RA management. In this review article, we present a systematic review of MTX effectiveness in reducing the risk of bone erosion. We reviewed randomized controlled trial studies that involved MTX monotherapy or MTX in combination with placebo. Evaluation of the progression of bone erosion was examined by radiographic assessment such as total Sharp score (TSS) or van der Heijde score (SvdH or vdH TSS), joint space narrowing (JSN), erosion score (ERO), and proportion of radiographic nonprogressors. Several key factors were found to influence the response to MTX treatment, such as gene polymorphism. The exact mechanism of the prevention of bone erosion by MTX remains unclear, which warrants future investigations. The variability of RA disease activity in study subjects resulted in variations in the results reported by individual studies. Collective analysis suggests that MTX could slow down the progression of bone erosion based on a radiographic score of less than 0.5-1/year.
33059295 Rheumatoid arthritis-related lung disease detected on clinical chest computed tomography i 2020 Dec OBJECTIVE: We aimed to determine the real-world prevalence and investigate risk factors for rheumatoid arthritis (RA)-related lung disease on chest computed tomography (CT) imaging. We also investigated the impact of RA-related lung disease on mortality. METHODS: We studied chest CT imaging abnormalities among RA patients. We determined the presence and type of abnormalities using the chest CT imaging radiologic report. RA-related lung disease was defined as interstitial lung disease (ILD), bronchiectasis, or pleural disease. We examined whether demographics and RA characteristics were associated with RA-related lung disease using logistic regression. RA-related lung disease and mortality was described using survival curves and Cox regression. RESULTS: We analyzed 190 patients who had chest CT imaging performed for clinical indications. Mean age was 64.2 years (SD 11.8), 80.0% were female, and 75.3% were seropositive. RA-related lung disease was detected in 54 patients (28.4%); 30 (15.8%) had ILD, 27 (14.2%) had bronchiectasis, and 18 (9.5%) had pleural disease. RA-related lung disease was reported in both seropositive and seronegative RA (28.7% vs. 27.7%, p = 1.00). Male sex (OR 2.62, 95%CI 1.17-5.88) and current methotrexate use (OR 2.73, 95%CI 1.27-5.61 vs. not current) were associated with RA-related lung disease. Twenty-four (44.4%) patients with RA-related lung disease died during mean 7.0 years of follow-up. RA-related lung disease had HR of 5.35 (95%CI 0.72-39.9) for mortality compared to normal chest CT. CONCLUSIONS: In this real-world study, RA-related lung disease was commonly detected on chest CT imaging regardless of RA serostatus. RA-related lung disease had high mortality, emphasizing the importance in close monitoring of these patients.
31611592 Folyl polyglutamate synthethase (FPGS) gene polymorphisms may influence methotrexate adver 2020 Apr The aim of the study was to look for the association of FPGS 2752 G > A (rs1544105), FPGS 1994 A > G (rs10106), and GGH 452 C > T (rs 11545078), GGH -401C > T (rs 3758149) gene polymorphisms with methotrexate (MTX) treatment response and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). Further the influence of these gene polymorphisms on MTX polyglutamate levels was analyzed. A total of 330 patients with RA were investigated. FPGS gene polymorphisms were analyzed by TaqMan 5'nuclease assay and GGH gene polymorphisms were analyzed by PCR-RFLP. Methotrexate polyglutamates (nmol/L of packed erythrocytes) were measured by liquid chromatography mass spectrometry (LCMS/MS) method. We found that the heterozygous genotype of FPGS rs1544105 [p = 0.02, OR 1.93, 95% CI (1.15-3.35)] and FPGS rs10106 AG genotype [p = 0.01, OR 2.11, 95% CI (1.20-3.71)] were associated with MTX adverse events. FPGS rs1544105 and GGH -401C > T SNPs influenced the polyglutamate levels. None of the investigated SNPs seems to be associated with MTX treatment outcome.
32117312 Rheumatoid Arthritis Patients, Both Newly Diagnosed and Methotrexate Treated, Show More DN 2020 Background: Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4(+) T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4(+) T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4(+) T cell populations (CD4(+) memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N = 11), methotrexate (MTX) treated RA patients (N = 18), and healthy controls (N = 9) matched for age, gender and smoking status. Results: Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4(+) memory than in CD4(+) naïve T cells (904 vs. 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (±500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbor both the lead RA risk SNP and two DMPs in CD4(+) memory T cells. Conclusion: Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.
31589126 Etiological Features of Liver Involvement in Rheumatoid Arthritis. 2020 BACKGROUND: Liver involvement is not considered a typical extra-articular manifestation and has rarely been studied in rheumatoid arthritis (RA). We aimed to identify the prevalence and aetiologies of liver disease in RA patients. METHODS: A cross-sectional study included 150 patients with RA enrolled over 5 years (2010- 2015). The clinical and paraclinical features of RA were analyzed. The clinical and biological characteristics of liver impairment and its aetiologies were collected. RESULTS: One hundred and fifty RA patients (124 women) with a mean age of 57.09 years and a mean RA duration of 7.52 years were included. Liver involvement was diagnosed in 66 patients (44%). The liver disease was asymptomatic in 94% of the cases, revealed by increased gammaglutamyl transferase levels in 74% of the patients. The aetiologies of liver involvement were hepatotoxicity of medications in 38 cases (57%), hepatitis B and C in 14 patients (21%), fatty liver disease in 10 cases (15%), autoimmune liver disease in 2 patients (3%), hydatid cyst in 1 case (2%), and liver angiomas in 1 case (2%). Non-steroidal anti-inflammatory drugs and methotrexate were the drugs most often involved in the genesis of hepatotoxicity (21% and 20% of the cases, respectively). CONCLUSION: Liver involvement occurred in 44% of RA patients. Aetiologies were mainly hepatotoxicity and viral hepatitis B and C. Patients with RA should be systematically screened for liver disease, which is rarely symptomatic.
33128201 Epidemiology and Treatment of Patients with Rheumatoid Arthritis, Psoriatic Arthritis and 2021 Jan INTRODUCTION: Rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PSO) are chronic inflammatory diseases that have a substantial impact on patients' health. This retrospective database study aimed to assess the epidemiology, comorbidities, diagnosis and treatment patterns of RA, PsA and PSO in the German population. METHODS: Data were extracted from the Deutsche Forschungsdatenbank für Abrechnungsinformationen der Krankenversicherung database from 2012 to 2016 for patients aged ≥ 18 years holding full health coverage in the reporting year at least. Diagnoses were defined according to International Classification of Diseases (ICD)-10 codes. Reported outcomes included prevalence and incidence rates, pre-defined comorbidities, diagnosing and treating physicians, and treatment exposure. A subgroup analysis was performed for women of childbearing age (females aged 18-45 years). RESULTS: The prevalence rates of RA, PsA and PSO in Germany were consistent over the study period; by 2016 they were 0.4%, 0.3% and 2.1%, respectively, and in women of childbearing age they were 0.2%, 0.2% and 1.5%, respectively. RA, PsA and PSO were predominantly observed among patients aged > 45 years. RA and PsA were more prevalent in women, while PSO had an approximately equal gender distribution. Depressive episodes were the most frequently reported comorbidity in 2016 (RA: 25.7%; PsA: 25.1%; PSO: 17.8%), and this was similar in women of childbearing age (RA: 20.5%; PsA: 23.4%; PSO: 16.3%). Approximately 50% of patients with RA and PsA and 6% of patients with PSO were receiving systemic treatment in 2016, of which methotrexate (RA: 38.4%; PsA: 30.2%; PSO: 2.2%) was most common. Biologic therapies were the least frequently used treatment options (RA: 28.9%; PsA: 20.9%; PSO: 1.8%). CONCLUSIONS: This analysis provides key epidemiological information for patients with RA, PsA and PSO, including in women of childbearing age, in Germany and highlights common comorbidities and that patients were likely receiving insufficient treatment for these diagnoses.
32628710 Effect of methotrexate use on the development of type 2 diabetes in rheumatoid arthritis p 2020 BACKGROUND: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.
33081546 Possible environmental exposure-associated pulmonary cryptococcosis in a patient with rheu 2020 Oct Patients with rheumatoid arthritis (RA) taking long-term immunosuppressive drugs are more susceptible to opportunistic infections, such as cryptococcosis. A 65-year-old woman was transferred to our hospital for rapidly progressing pulmonary lesions identified by lung computed tomography. She had a 7-year history of RA and had been prescribed methotrexate and glucocorticoids for 10 months. Additionally, our patient had a history of environmental exposure to house renovation lasting approximately 1 week before onset. Her serological test results and histopathological examination confirmed the diagnosis of pulmonary cryptococcosis (PC). The patient recovered well after 6 months of fluconazole treatment. In addition, we summarized 28 reported cases of RA patients with PC and found that older age might be a risk factor for cryptococcal infection in RA patients. The most common location for pulmonary lesions was the lower lobe, and the most common radiologic manifestations were nodules. Detection of cryptococcal capsular polysaccharide antigen was important for diagnosis. Patients undergoing antirheumatic therapy should avoid exposure to Cryptococcus.
31598719 Differential DNA methylation correlates with response to methotrexate in rheumatoid arthri 2020 Jun 1 OBJECTIVES: Identifying blood-based biomarkers that predict treatment response in RA is a clinical priority. We investigated differential DNA methylation as a candidate biomarker of response for the first-line drug used in RA, MTX. METHODS: DNA methylation was measured in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study. Differentially methylated positions were compared between whole blood samples collected at baseline and at 4 weeks from patients who, by 6 months, had a good (n = 34) or poor response (n = 34) to MTX using linear modelling, adjusting for gender, age, cell composition, baseline 28-joint disease activity score (DAS28) and smoking status. Analyses also compared methylation with changes in DAS28 and changes in swollen joint count and tender joint count, and changes in CRP over the initial 6 months after MTX commencement. Differentially methylated positions showing significant differences with any response parameter were tested using pyrosequencing in an independent group of 100 patients from the Rheumatoid Arthritis Medication Study. RESULTS: In the discovery group, two CpG sites showed methylation changes at 4 weeks associated with clinical EULAR response by 6 months. Significant changes in methylation for three differentially methylated positions associated with change in tender joint counts, three with change in swollen joint count and a further four with change in CRP. Of the 12 CpGs, four showed replicated association in an independent dataset of samples from the Rheumatoid Arthritis Medication Study. CONCLUSION: These data represent an advance on current practice by contributing to a personalized medicine strategy allowing an escalation or change in therapy as early as 4 weeks.
30629341 Clinical and Structural Efficacy of Hydroxychloroquine in Rheumatoid Arthritis: A Systemat 2020 Jan OBJECTIVE: Hydroxychloroquine (HCQ) improves metabolic and cardiovascular outcomes in patients with rheumatoid arthritis (RA), but its efficacy appears to be moderate as compared to placebo. The aim of our study was to assess the current literature on the clinical and structural efficacy of HCQ in the joints of patients with RA. METHODS: We systematically searched MEDLINE (via PubMed), Embase, Cochrane Library, and the American College of Rheumatology and European League Against Rheumatism annual scientific meeting abstracts for studies available up to November 2017 comparing the efficacy of HCQ in patients with RA, in monotherapy or combined with other conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Data were extracted by 1 investigator and independently checked by a different investigator. RESULTS: The literature search revealed 197 articles and abstracts of potential interest, and 11 studies fulfilled inclusion criteria. The clinical and structural efficacy of HCQ was similar to or lower than that for methotrexate or sulfasalazine in monotherapy. HCQ combined with other DMARDs could increase the clinical efficacy. CONCLUSION: In addition to its metabolic benefit, combining HCQ with other DMARDs could provide some clinical improvement in patients with RA and inadequate response to previous csDMARDs.
32669456 Does autoimmune thyroid disease affect rheumatoid arthritis disease activity or response t 2020 Jul OBJECTIVE: To investigate if autoimmune thyroid disease (AITD) impacts rheumatoid arthritis (RA) disease activity or response to methotrexate. METHODS: A nationwide register-based cohort study of 9 004 patients with new-onset RA from the Swedish Rheumatology Quality Register year 2006-2016, with linkage to other nationwide registers to identify comorbidity with AITD defined as thyroxine prescription before RA diagnosis, excluding non-autoimmune causes. We compared RA disease activity using 28-joint Disease Activity Score (DAS28) and its components, and EULAR response, between patients with and without AITD, using logistic regression. RESULTS: At diagnosis, patient reported outcome measures (PROMs; patient global, Health Assessment Questionnaire Disability Index and pain) but not objective disease activity measures (erythrocyte sedimentation rate and swollen joint count) were significantly higher (p<0.05 for all PROMs) among RA patients with AITD compared with those without. The level of DAS28 was 5.2 vs 5.1. By contrast, AITD had little influence on EULAR response to methotrexate at 3 months (OR of non/moderate response=0.95, 95% CI 0.8 to 1.1), nor at 6 months. When stratified by age, however, AITD was more common among EULAR non/moderate responders at 3 and 6 months in patients below 45 years resulting in ORs of non/moderate response of 1.44 (0.76-2.76) and 2.75 (1.04-7.28). CONCLUSION: At diagnosis, RA patients with concomitant AITD score worse on patient reported but not on objective RA disease activity measures, while DAS28 was only marginally elevated. The overall chance of achieving a EULAR good response at 3 or 6 months remains unaffected, although among a limited subgroup of younger patients, AITD may be a predictor for an inferior primary response.
32783547 Vitamin D: does it help Tregs in active rheumatoid arthritis patients. 2020 Aug Background Regulatory T cells (Tregs) play an important role in the maintenance of immunological tolerance. Tregs deficiency or suppressor functions reduction may be associated with autoimmune diseases development. Objectives To estimate the effect of vitamin D supplementation on Tregs level in the peripheral blood of active rheumatoid arthritis (RA) patients. Methods 40 active RA patients were randomly assigned into two groups. Group I received methotrexate (MTX) plus hydroxychloroquine, group II received MTX, hydroxychloroquine plus vitamin D supplementation for 3 months, and 30 healthy volunteers as control group. Peripheral blood Tregs were measured at baseline and after 3 months by Flow Cytometry. Results At baseline, Tregs percentage was significantly decreased (p<0.001) in both RA patient groups (13.52±1.95%, 13.65±2.98% respectively), compared to controls (28.44±7.37%) with no significant difference between the two patient groups (p=0.866). After 3 months, there was a significant elevation in Tregs percentage in group II compared to group I (p<0.001). Tregs elevation was associated with significant DAS-28 score reduction (p<0.001). Conclusion Vitamin D appears to have important immunomodulatory functions. Vitamin D supplementation can be combined safely with traditional DMARDs to regulate the immune system. Clinical trial registration Tanta University Protocol Record 33846, Vitamin D Effect in Rheumatoid Arthritis, http://www.clinicaltrials.gov, NCT04472481.
33153331 Status of fracture risk assessment and osteoporosis treatment in Japanese patients with rh 2021 Sep OBJECTIVES: This study aimed to investigate the prevalence of patients with rheumatoid arthritis (RA) at a high risk of major osteoporosis (OP)-related fractures and the status of OP-related medical treatment for these patients. METHODS: We enrolled 120 patients aged ≥40 years (average, 69.1 years) with RA. The Fracture Risk Assessment Tool (FRAX(®)) was used to evaluate the fracture risk. Of the 120 patients, the femoral neck bone mineral density (BMD) was evaluated in 102 patients, and their FRAX(®) scores were calculated alongside the BMD values. Patients observed to be at a high risk of a major OP-related fracture (10-year probability >20% or hip fracture risk >3%), according to FRAX(®), were identified as those requiring OP treatment; medication ratio for OP (percentage of patients actually receiving medication among patients requiring OP treatment) was assessed. RESULTS: OP treatment was indicated in 75 (63%) patients; the medication ratio for OP was 49%. The use of biological disease-modifying anti-rheumatic drugs and corticosteroids showed a positive effect; however, the use of methotrexate showed a negative effect on the medication ratio. CONCLUSION: The number of potential patients requiring OP treatment is underestimated. All patients with RA should be assessed to determine their eligibility for OP treatment.
32582145 Adipokines and Inflammation Alter the Interaction Between Rheumatoid Arthritis Synovial Fi 2020 Objective: The long-distance migration of rheumatoid arthritis synovial fibroblasts (RASFs) in the severe combined immunodeficiency (SCID) mouse model of rheumatoid arthritis (RA) suggests that an interaction between RASFs and endothelial cells (EC) is critical in this process. Our objective was to assess whether immunomodulatory factors such as adipokines and antirheumatic drugs affect the adhesion of RASFs to ECs or the expression of surface molecules. Methods: Primary ECs or human umbilical vein endothelial cell (HUVEC) and primary RASFs were stimulated with adiponectin (10 μg/mL), visfatin (100 ng/mL), and resistin (20 ng/mL) or treated with methotrexate (1.5 and 1,000 μM) and the glucocorticoids prednisolone (1 μM) and dexamethasone (1 μM), respectively. The expression of adhesion molecules was analyzed by real-time polymerase chain reaction. The interaction of both cell types was analyzed under static (cell-to-cell binding assay) and dynamic conditions (flow-adhesion assay). Results: Under static conditions, adipokines increased mostly binding of RASFs to EC (adiponectin: 40%, visfatin: 28%, tumor necrosis factor α: 49%). Under flow conditions, visfatin increased RASF adhesion to HUVEC (e.g., 0.5 dyn/cm(2): 75.2%). Reduced adhesion of RASFs to E-selectin was observed after treatment with dexamethasone (e.g., 0.9 dyn/cm(2): -40%). In ECs, tumor necrosis factor α (TNF-α) increased expression of intercellular adhesion molecule 1 (20-fold) and vascular cell adhesion molecule 1 (77-fold), whereas P-selectin was downregulated after stimulation with TNF-α (-6-fold). Conclusion: The adhesion of RASFs to EC was increased by visfatin under static and flow conditions, whereas glucocorticoids were able to decrease adhesion to E-selectin. The process of migration and adhesion of RASFs to ECs could be enhanced by adipokines via adhesion molecules and seems to be targeted by therapeutic intervention with glucocorticoids.