Profile Of Rheumatoid Arthritis Patients Research Articles

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

Demographic, Clinical Profile of Rheumatoid Arthritis Patients and Their Association with Disease Severity in Ghana.

Rheumatoid arthritis (RA) is one of the frequent chronic, systemic, inflammatory autoimmune disorders with an estimated global prevalence of 1%. RA leads to joint destruction and disability if left untreated. Ghana has seen very few studies on RA, and little is known about the disease's severity and related variables. This study sought to characterize the clinical presentation and determine disease severity and associated risk factors with disease severity among RA patients in a tertiary hospital in Ghana. This cross-sectional study was conducted between September 2020 and August 2021. This study included 56 consecutively consenting RA patients from the Komfo Anokye Teaching Hospital orthopaedic unit. Diagnosis of RA was based on the updated American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2022 rheumatoid arthritis classification criteria by a rheumatologist. A study questionnaire was used to gather participant demographics and clinical features, and results from the laboratory were taken from the patients' charts and medical records. The patients' disease severity was evaluated based on the rheumatoid arthritis disease activity score, which is based on a 28-joint count (DAS28), and their functioning was evaluated using the modified health assessment questionnaire. The participants' mean age was 51.25 ± 13.22 years. Out of the total participants, 46 were females, and 10 were males (female-to-male ratio 4.6 : 1). Moreover, 37.50% had arthritis of the hand; 5.30% had severe disease, and 94.60% were not severe. A majority (76.80%) were on methotrexate medication. The most frequently involved joints were the knee (42.90%), wrist (32.10%), and elbow (12.50%). There was no statistically significant association with disease severity and a functional status score of >0.5 (cOR: 10.60, 95% CI (0.52-217.30); p = 0.124). In addition, marital status (p = 0.04), disease duration (p = 0.04), family complaints (p = 0.02), and ESR (p = 0.03) were significantly associated with disease severity. RA is predominant among elder populations and females. Disease duration, family complaints, and ESR are associated with disease severity. The findings of this study call for interventions towards ensuring early diagnosis of RA among high-risk populations to enhance good management practices.

Evaluation of the deleted in malignant brain tumor 1 protein expression and DNA methylation profile in rheumatoid arthritis patients

Evaluation of the deleted in malignant brain tumor 1 protein expression and DNA methylation profile in rheumatoid arthritis patients

Cost-consequence of abatacept as first-line therapy in Japanese rheumatoid arthritis patients using IORRA real-world data.

To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers.

Split Dosage Weekly Regimen of Oral Methotrexate is Associated With Improved Side Effect Profile in Rheumatoid Arthritis Patients: A Quasi-Experimental Study.

Background and objectivesMethotrexate (MTX) is globally used by physicians to treat patients with Rheumatoid Arthritis (RA). Previously conducted researches indicate prevalent side effects associated with conventional once-weekly dosage amongst a population sample of patients consuming MTX. The objectives of our study were to find out whether there is a difference between the two studied regimens in efficacy and adverse effects of methotrexate.Materials and methodsStudy participants were recruited from the outpatient rheumatology department after ethical approval and informed patient consent. Disease activity was assessed at baseline with various reliable and validated scales (SDAI, PAS, DAS-28 among others) after the propensity score-matched 1:1 among the two groups. One group continued their once-weekly regimen (group A), while the other group had their dosage of oral MTX split into alternate days per week (group B). The propensity-matched groups of 123 patients each were included in the final analysis.ResultsThe most frequently reported side effect was decreased appetite, followed by gastritis, nausea, headache, and vomiting. Within the two groups, no significant differences were found in disease activity scales. The only considerable difference was mean corpuscular volume (MCV) being higher in Group A (p = 0.0128). Comparison of side effect profile at 6 months after intervention showed improved gastritis (63.4 vs 41.5%), nausea (51.2% vs 35.8%), appetite (74.0% vs 60.2%) and hepatotoxicity (14.6% vs 5.7%) in Group B.ConclusionAn alternate-day regimen may prove more beneficial to the patient’s compliance due to fewer side effects and similar efficacy to the conventional dosage.

Lipid profile changes in patients with rheumatoid arthritis and autoimmune thyroiditis

The data about changes in lipid profile in rheumatoid arthritis patients with autoimmune thyroiditis is given in the article.

MYD88, IRAK3 and Rheumatoid Arthritis pathogenesis: Analysis of differential gene expression in CD14 + monocytes and the inflammatory cytokine levels

Rheumatoid arthritis (RA) is a well-known chronic inflammatory disorder. Two molecular players act in the inflammation balance of the disease: MyD88 (Myeloid differentiation primary response 88) is related to TLR (Toll-like receptors) response and promotes the formation of myddosome complex resulting in increased inflammation; IRAK3 (Interleukin-1 receptor associated kinase 3) acts suppressing the myddosome complex thus decreasing inflammation. In this scenario, MYD88 and IRAK3 gene expression profile in RA patients and its correlation with clinical features is still partially known. So, we evaluated the MYD88 and IRAK3 gene expressions in CD14 + monocytes from RA patients and healthy controls and its relation with patients’ clinical features and cytokine plasma levels. CD14 + monocytes were isolated using positive selection by magnetic cell separation. The MYD88 and IRAK3 gene expressions were measured through real time relative quantitative PCR with specific primers; relative quantification was normalized to ACTB, GAPDH, 18S and RPLP0 reference genes. Cytokine levels were analyzed by CBA (cytokine beads assays). CD14 + monocytes from RA patients showed lower IRAK3 expression level compared to controls although with a borderline statistical significance (Fold change (FC) = -1.63; p = 0.054). Furthermore, RA patients with high disease activity had lower levels of IRAK3 when compared to patients with low/moderate activity measured by the CDAI index (FC = -1.78; p = 0.030). No significant differences were observed for MYD88 gene expression (FC = 1.20; p = 0.294) between patients and controls analyzed. Additionally, we did not we did not observe correlation between IRAK3 and MYD88 gene expression and TNF-α, IL-6, IL-2 and IL-10 levels. We suggested that IRAK3 gene expression in CD14 + monocytes appears to be relevant to the RA etiology and clinical activity, whereas, in this study, MYD88 does not play a role in RA onset and development.

Effect of Biologics on Cardiovascular Inflammation: Mechanistic Insights and Risk Reduction.

It is increasingly recognized that atherosclerosis and consequently cardiovascular disease (CVD) are closely linked with inflammatory processes. The latter is in the center of the pathogenic mechanism underlying autoimmune rheumatic diseases (ARD). It follows then, that optimal control of inflammation in ARDs may lead to a decrease of the accompanied CVD risk. Major trials (eg, CANTOS, CIRT), aimed at examining the possible benefits of immunomodulatory treatments in CVD, demonstrated conflicting results. On the other hand, substantial evidence is accumulating about the possible beneficial effects of biologic disease modifying antirheumatic drugs (bDMARDs) in patients with ARDs, particularly those with rheumatoid arthritis (RA). It seems that bDMARDs (some more than others) alter the lipid profile in RA patients but do not adversely affect, in most cases, the TC/HDL ratio. Favorable effects are noted for arterial stiffness and endothelial function. This is reflected in the lower risk for CVD events, seen in observational studies of RA patients treated with bDMARDs. It should be stressed that more data exist for the TNF-inhibitors than for other bDMARDs, such as tocilizumab, abatacept and rituximab. As regards the spondyloarthropathies (SpA), data are less robust. For TNF-inhibitors, effects appear to be on par with those seen in RA but no conclusions can be drawn for newer biologic drugs used in SpA (eg, IL-17 blockers). Finally, there is accumulating evidence for a beneficial effect of immunosuppressive treatment in cardiac inflammation and function in several ARDs. Introduction of newer therapeutic options in clinical practice seem to have a positive impact on CVD in the setting of ARD. This is probably due to better control of inflammation, but direct improvement in vascular pathology is also a valid hypothesis. Most data are derived from observational studies and, therefore, randomized controlled trials are needed to assess the possible favorable effect of bDMARDs on CVD outcomes.

Features of dyslipidemia and its influence on endothelium functional state in patients with rheumatoid arthritis and arterial hypertension

Purpose of the study. Was to identify the features of blood lipid spectrum and endothelium functional state in patients with rheumatoid arthritis (RA) and arterial hypertension (AH).&#x0D; Materials and methods. 83 patients were examined (40 with RA combined with AH, 23 with RA and 20 with AH). The blood lipid spectrum and endothelial function were studied in all patients.&#x0D; Results. The analysis of blood serum lipid parameters demonstrated that in patients with RA, regardless of the presence of AH, there was a significant increase of proatherogenic lipid profile parameters in comparison with those in healthy subjects. It was shown, that lower concentrations of high-density lipoproteins and higher atherogenic coefficient indices was a characteristic feature of the lipid profile in RA patients both with and without AH – in contrast to the same parameters of the lipid spectrum in patients with AH without RA. In the groups of patients with RA a significant increase of the brachial artery diameter at rest and decreased indices of endothelium-dependent vasodilation and endothelium-independent vasodilation were revealed. Subjects with RA in combination with AH had significantly lower indices according to the tests with both reactive hyperemia and nitroglycerin, while in patients with RA without AH, only NG-test was significantly lower.&#x0D; Conclusion. Dyslipidemia of atherogenic type and endothelial dysfunction develops at the initial stages of rheumatoid process and depends on the activity of the inflammatory process, the presence of extra-articular manifestations and rheumatoid factor seropositivity.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5–1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.

Impact of Mediterranean Diet on Disease Activity and Gut Microbiota Composition of Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome; previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein (p < 0.037) and disease activity (p < 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of Prevotella copri with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.

Whole exome sequencing (WES) of methotrexate response/adverse event profile in rheumatoid arthritis patients

Aim of the workTo preliminary study polymorphisms in a set of genes of relevance to methotrexate (MTX) response based on the Drug Bank database in Egyptian rheumatoid arthritis (RA) patients. Patients and methodsThe study included 10 consecutive adult female RA patients categorized according their response and adverse events (AEs) to MTX; patients with good response, ACR50 after 4 weeks was considered. Variant Call Format files were annotated and filtered via Drug Bank (11/9/2017) database in MTX. Accordingly, the following set of genes most related for RA MTX response were considered: SLC16A1, SLC7A11, SLC22A7, TBXAS1, PTK2B, ABCC2, ABCC4, SNORD13G, SLCO3A1, ABCC1, SLC46A1, SARM1, ABCB1, SLC19A, ATIC and SLCO1C1. Human genome DNA was assessed using Ion Ampliseq Exome Panel. Single-nucleotide variants (SNVs) and short insertions/deletions were identified ResultsThe mean age of the patients was 39 ± 12.5 years and disease duration 9.8 ± 7.4 years. AEs were present in 4 (2 poor and 2 good responders). 6 patients showed a good response with no AEs. Of the 16 studied genes, 19 variants were revealed. 18 SNVs and one deletion were detected. The C allele of ABCB1 was dominant in 7 out of 8 good responders’ (87.5%). The G of ATIC was present in 20% with AEs and poor response. The T and G of SLCO1C1 were in 60% of good responders. ConclusionIn Egyptian RA patients, there is evidence of a possible influence of a set of gene variants on the disease pathogenesis while others were related to MTX AEs and response.

PON-1 haplotype (-108C>T, L55M, and Q192R) modulates the serum levels and activity PONase promoting an atherogenic lipid profile in rheumatoid arthritis patients.

Paraoxonase 1 (PON1) promotes antioxidant and antiatherogenic activity related to the hydrolysis of oxidized lipids of low-density lipoproteins. In rheumatoid arthritis (RA) patients, it has been reported that low PON1 activity is related to an impaired lipid profile, increasing cardiovascular risk (CVR). The goal of this study was to analyze the effect of common PON1 polymorphisms and haplotypes on enzymatic activity, PON1 serum levels (PON1s), and lipid parameters related to atherogenic profile in RA patients. A cross-sectional study was carried out on 250 Mexican patients with RA. The lipid profile was determined by colorimetric tests. The PON1 activity (CMPAase) was measured by spectrophotometry. The levels of PON1s were determined by ELISA, and the polymorphisms in the PON-1 gene (-108C>T, L55M, and Q192R) were genotyped by the PCR-RFLP method. The haplotypes were estimated and statistical analysis was performed. The median of the CMPAase activity and PON1 levels was 13.91U/mL and 24.75ng/mL, respectively. The CMPAase activity was significantly lower in carriers of -108TT and 192QQ genotypes (β = - 4.09, P = 0.001 and β = - 3.73, P = 0.002, respectively); moreover, the PON1 levels were lower in 192Q allele carriers (P < 0.01). The TLQ haplotype was associated with CMPAase activity < 13.91U/mL (OR = 2.29, P < 0.001), as well as with levels of PON1s < 24.75ng/mL (OR = 1.65, P = 0.017). In this study, the CMPAase activity (< 13.91U/mL) showed a positive association with lower levels of high-density lipoprotein cholesterol (HDL-c; < 40/50mg/dL), and with a triglycerides/HDL-c ratio > 3%, and a total cholesterol/HDL-c ratio > 4.5/5%, all representatives of an atherogenic risk lipid profile. PON1 polymorphisms modulate the CMPAase activity and PON1 levels in Mexican patients with RA. The CMPAase activity < 13.91U/mL is associated with an atherogenic lipid profile, independently of inflammation markers and treatment with anti-rheumatic drugs. Key Points •The haplotype TLQ is a marker for low PONase activity in rheumatoid arthritis. •The haplotype TLQ is a marker for low PON1 serum levels in rheumatoid arthritis. •The enzymatic PON1 activity represents the best marker for an atherogenic lipid profile in rheumatoid arthritis, in comparison with PON1 levels. •The haplotype TLQ is a marker of low PON1 activity, levels of PON1s, and atherogenic lipid profile, independent of treatment therapy in rheumatoid arthritis.

AB0185 PROSPECTIVE PROFILE OF URINE METABOLOME IN RHEUMATOID ARTHRITIS

Background:Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by increased mortality and associated with metabolic disorders. Since the metabolomic profile is known to vary in response to different inflammatory conditions, metabolome analysis could substantially improve diagnosis and prognosis of RA.Objectives:To analyze the urine metabolome profile in RA patients and correlate it with disease activity changes over 12 monthsMethods:Seventy-nine RA patients, according to ACR/EULAR 2010 classification criteria, between 40 and 70 years old, were recruited and followed for 12 months. Metabolome analysis was performed by Nuclear Magnetic Resonance spectroscopy (NMR), resulting in the identification of 93 metabolites in urine collected at the baseline and after 12 months. Frequency analysis, Pearson Correlation and Multivariate data analysis with orthogonal projections to latent structures (OPLS) method were performed and a statistical significance was considered as p&lt;0.05.Results:The study population was characterized by the majority of women (86.7%), mean age of 56 years old, around 80% with positive anti-CCP or Rheumatoid Factor. During the one year of follow-up, there was no substantial variation in the DAS28 measurement (baseline: 3.8, after 12 months: 4.0). There was no significant correlation between the metabolome pattern and DAS28 score (p&gt;0.05) over time. However, multivariate analysis (OPLS-DA) demonstrated an adequate differentiation of the population with 0.92 of accuracy (Q2: 0.72 and R2: 0.89).There was a significant increase of L-cysteine, choline, L-Phenylalanin, creatine, L-histidine, oxalacetic acid and xanthine, and a decrease of L-threonine, taurine, butyric and gluconic acid (p&lt;0.05) during the follow-up, metabolites that are involved in the skeletal muscle metabolism.Conclusion:The observed biomarkers indicate,as expected, that the RA metabolic profile is associated with inflammation injury and skeletal muscle amino acid metabolism. Correlations with disease activity changes was compromised by the stable disease status during the 12 months. More studies evaluating correlations with skeletal muscle function and mass are underway.Acknowledgments:Disclosure of interest: Marianne Oliveira: None declared, Rafaela Santo: None declared, Mirian Farinon: None declared, Ricardo Xavier Consultant of: Abbvie, Pfizer, Novartis, Janssen, Lilly, RocheDisclosure of Interests:Marianne de Oliveira: None declared, Paulo Vinicius Alabarse: None declared, Mirian Farinon: None declared, Rafaela Cavalheiro do Espírito Santo: None declared, Ricardo Xavier Consultant of: AbbVie, Pfizer, Novartis, Janssen, Eli Lilly, Roche

Clinical Profile of Rheumatoid Arthritis Patients Reporting to a Tertiary Care Center – Data From Southwestern Part of India

Clinical Profile of Rheumatoid Arthritis Patients Reporting to a Tertiary Care Center – Data From Southwestern Part of India

A Comparative Study of Interleukin 6, Inflammatory Markers, Ferritin, and Hematological Profile in Rheumatoid Arthritis Patients with Anemia of Chronic Disease and Iron Deficiency Anemia.

Background Interleukin-6 (IL-6) proinflammatory cytokine is associated with the pathogenesis of rheumatoid arthritis and development of anemia in it. This is a comparative study of inflammatory and hematological parameters in RA patients with anemia of chronic disease (ACD) and iron deficiency anemia (IDA). It aimed to demonstrate the changes in serum level of IL-6, ferritin level, and hematological parameters in different groups of patients with RA and to find out the potential correlation between serum level of IL-6 and ferritin level and the relationship between serum level of IL-6 and iron status. Methods The study included 89 patients from both sexes divided into four groups (group 1: 30 iron deficiency anemia (IDA), 59 RA; group 2: 20 RA-COMBI; group 3: 23 RA-ACD; and group 4: 16 nonanemic RA). These different groups were compared with a healthy group of 50 healthy individuals. Different blood parameters (WBC, RBC, HGB, HCT, MCV, and MCH) have been evaluated. Serum concentrations of IL-6, hsCRP, anti-CCP, and ferritin were measured in all patients and healthy individual using enzyme-linked immunosorbent assay ELISA. Results There were significant changes in most of blood parameters between the groups, and there was a significant increase in the levels of IL-6 among RA patients. This increase was highly significant among RA-ACD patients in particular, and this elevation has been directly correlated with clinical indices of disease activity such as hsCRP, ESR, anti-CCP, and ferritin. There was an inverse relationship between ferritin and all iron status parameter, such as RBC, HGB, and haematocrit. Conclusion IL-6 and ferritin level estimation may be workable tests to differentiate the patients with IDA and ACD in RA.

Gender Differences in Cardiovascular Risk Profile in Rheumatoid Arthritis Patients with Low Disease Activity.

Objective Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular (CV) disease (CVD). The objective of the study was to compare CV risk profile in female and male RA patients with low disease activity. Materials and Methods The study group consisted of 70 RA patients with continuous low disease activity and no CVD (54 women, 16 men) and 33 healthy controls of comparable age. The groups were assessed for blood pressure, serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), carotid intima media thickness (cIMT), electrocardiography, ejection fraction (EF), and diastolic dysfunction (DD). Results Significantly higher burden of atherosclerosis, as revealed by higher cIMT, was found in males [0.93 (0.2) mm] vs females [0.80 (0.2) mm]. The risk of 10-year CVD was significantly higher in men than in women with RA. High/very high risk of fatal CVD was found in 62.5% of male patients. Males were significantly more often current/ex-smokers and had lower HDL-cholesterol and higher atherogenic index. There were no significant differences in NT-proBNP, QTc duration, and parameters of EF and DD. Conclusions In RA patients with continued low disease activity, a higher burden of atherosclerosis was found in males than in females. The data suggest a significant impact of traditional CV risk factors.

Efficacy and safety of add‐on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate

To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients. This was a 24-week multi-center, double-blind, randomized, non-inferiority study targeting RA patients with moderate to severe Disease Activity Score of 28 joints (DAS28>3.2) who showed inadequate response to MTX. Patients were randomized into TAC or LEF (add-on to MTX) groups. Initial daily doses of TAC and LEF were 1.5 and 10mg, respectively, for 4weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24weeks. Eighty-seven patients were screened in 10 centers and 75 patients were randomized into two groups. Baseline demographics were comparable between TAC+MTX and LEF+MTX groups. The TAC+MTX group was non-inferior to the LEF+MTX group in terms of DAS28 at 24weeks (mean difference of DAS28: -0.1812, 95% confidence interval: -0.8073, 0.4450). There was a greater number of adverse events in the LEF+MTX group (66 in LEF+MTX and 49 in TAC+MTX). Six patients presented with transaminitis in the LEF+MTX group compared with two patients in the TAC+MTX group. The efficacy of TAC combined with MTX was non-inferior to LEF+MTX. It had a reasonable safety profile in RA patients with moderate to severe disease activity (http://cris.nih.go.kr; KCT0000781).

Distinct Urinary Metabolic Profile in Rheumatoid Arthritis Patients: A Possible Link between Diet and Arthritis Phenotype

Objective. We undertook this study to investigate the discriminant metabolites in urine from patients with established rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and from healthy individuals. Methods. Urine samples were collected from 148 RA patients, 41 SLE patients and 104 healthy participants. The urinary metabolomic profiles were assessed using 1H nuclear magnetic resonance spectroscopy. The relationships between discriminant metabolites and clinical variables were assessed. Collagen-induced arthritis was induced in mice to determine if a choline-rich diet reduces arthritis progression. Results. The urinary metabolic fingerprint of patients with established RA differs from that of healthy controls and SLE patients. Markers of altered gut microbiota (trimethylamine-N-oxide, TMAO), and oxidative stress (dimethylamine) were upregulated in patients with RA. In contrast, markers of mitochondrial dysfunction (citrate and succinate) and metabolic waste products (p-cresol sulfate, p-CS) were downregulated in patients with RA. TMAO and dimethylamine were negatively associated with serum inflammatory markers in RA patients. In particular, patients with lower p-CS levels exhibited a more rapid radiographic progression over two years than did those with higher p-CS levels. The in vivo functional study demonstrated that mice fed with 1% choline, a source of TMAO experienced a less severe form of collagen-induced arthritis than did those fed a control diet. Conclusion. Patients with RA showed a distinct urinary metabolomics pattern. Urinary metabolites can reflect a pattern indicative of inflammation and accelerated radiographic progression of RA. A choline-rich diet reduces experimentally-induced arthritis. This finding suggests that the interaction between diet and the intestinal microbiota contributes to the RA phenotype. (J Rheum Dis 2019;26:46-56)

The Profile of Serum Transferrin Isoforms in Rheumatoid Arthritis.

Transferrin, a microheterogeneous iron-transporting N-glycoprotein, is an optimal model for the analysis of the glycosylation profile in rheumatoid arthritis (RA). The aim of this study was to assess the transferrin isoforms profile in RA patients at the time of diagnosis and then look into their associations with disease activity. Serum samples were collected from 48 patients with RA. The patients were males (6) and females (42) (age range: 33-85 years). Control group consisted of 30 healthy volunteers. Transferrin isoforms were analysed by capillary electrophoresis on MINICAP electrophoretic system. There was a significant decrease in the relative concentrations of trisialo- (mean ± SD; 2.130 ± 1.112) and pentasialotransferrin (13.562 ± 3.088), and significant increase in tetrasialotransferrin (83.640 ± 3.165) in RA patients when compared to the control group (3.615 ± 1.156; 76.840 ± 5.621; 18.610 ± 6.027, respectively) (U Mann-Whitney test: p < 0.001 for all comparisons). There were no significant changes in the disialotransferrin concentrations in RA patients. Trisialotransferrin concentration correlated with RA activity expressed as DAS 28 in RA patients (p < 0.001). The low trisialotransferrin concentration was also associated with high platelet count and high ESR (p < 0.001 for both). Disialo-, tetrasialo- and pentasialotransferrin concentrations did not correlate with DAS 28. In patients with RA the serum profile of transferrin isoforms is altered. We predict that the levels of trisialylated isoforms of transferrin will serve as a useful biochemical marker of the RA activity.