Group Of Rheumatoid Arthritis Patients Research Articles

Evaluation of central corneal thickness and corneal curvature in patients with rheumatoid arthritis

Background: Rheumatoid arthritis is an autoimmune disease. It is a chronic disease that causes symmetrical deforming type of polyarthritis. Rheumatoid arthritis most commonly involves the anterior segment of the eye. It causes keratoconjunctivitis sicca, episcleritis, scleritis, sclerosing keratitis, stromal keratitis, paracentral keratolysis, and peripheral ulcerative keratitis. Aims and Objectives: The purpose of this study was to evaluate central corneal thickness (CCT) and corneal curvature in patients with rheumatoid arthritis. We also evaluated the association between CCT, corneal curvature, and rheumatoid arthritis severity. Materials and Methods: A total of 49 rheumatoid arthritis patients and 49 control subjects were enrolled in this study. The study was conducted in the ophthalmology department of SRM medical college, Chennai. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was done using Shirmers test, tear breakup time, and corneal fluorescein staining. The CCT and corneal curvature were measured by ultrasonic pachymetry and auto keratorefractometer, respectively. For statistical analysis, we used chi-square test, Fisher exact test, student t-test, and ANOVA test. Results: Mean CCT in all rheumatoid arthritis patient group eyes was 532.78±14.03 micrometers. Mean CCT in rheumatoid arthritis with dry eye was 522.3±11.10 micrometer, in rheumatoid arthritis without dry eye was 536.90±11.60 micrometer and control patients’ group was 564.80±20 micrometer respectively. The difference of CCT was found to be statistically significant (P<0.05) between rheumatoid arthritis and control eyes. Mean corneal curvature was 42.71D±2.16 in all rheumatoid arthritis patients. Mean corneal curvature was 42.7D±1.6 in rheumatoid arthritis with dry eye, 42.8D±2.5 in rheumatoid arthritis without dry eye, and 42.5D±2.1 in control eye, respectively. Our result did not show statistically significant difference in corneal curvature between the rheumatoid arthritis patients and control patients. CCT and corneal curvature were not associated with rheumatoid arthritis activity and rheumatoid arthritis duration. Conclusion: The CCT was thinner in rheumatoid arthritis patients than control patients. In order to improve the quality of vision of rheumatoid arthritis patients, we suggest including pachymetry as a routine ophthalmic examination in them. Pachymetry will be helpful in diagnosing and guiding clinical treatment in these patients.

Increased serum adenosine deaminase activity in patients with adult-onset Still's disease

BackgroundAdult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology, lacking specific diagnosis and disease activity evaluation indicators. This study will analyze the activity and clinical significance of Adenosine deaminase (ADA) in AOSD patients.MethodsTotally 53 AOSD patients, 60 patients with other autoimmune diseases including systemic lupus erythematosus (SLE), sjogren syndrome (SS) and rheumatoid arthritis (RA), as well as 60 healthy subjects were included in this study. AOSD activity was determined by Pouchot score. We analyzed the correlation between ADA activity and clinical parameters. In addition, the correlation between ADA activity and disease activity score was also analyzed.ResultsThis study showed that the activity of ADA in AOSD patients was significantly higher than that of healthy controls, SLE, SS and RA patient groups (p < 0.0001). The ADA activity of AOSD patients decreased significantly after systemic treatment (p < 0.0001). Correlation analysis showed that ADA activity was positively correlated with ALT(r = 0.54, p < 0.0001), AST (r = 0.82, p < 0.0001) and serum ferritin (r = 0.67, p < 0.001). ADA activity was negatively correlated with white blood cell (r = − 0.42, p = 0.002) and platelet counts (r = − 0.44, p = 0.001). We also found a significant positive correlation between the activity of ADA and Pouchot score in AOSD patients (r = 0.51, p = 0.001). Receiver operating characteristic (ROC) curve analysis showed that ADA activity had a sensitivity of 93.3%, and a specificity of 83% for the diagnosis of AOSD, with an area under the curve of 0.93.ConclusionThis study showed that serum ADA activity can be used as a potential biomarker for AOSD diagnosis and disease activity assessment.

Оценка факторов риска в течении ревматоидного артрита и анкилозирующего спондилита

The purpose — to study individual risk factors and their influence on the course of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and methods. Patients with RA and AS took part in the research; the group of comparison was practically healthy people. We evaluated clinical condition and laboratory indicators (the level of cytokines, lymphocyte subpopulation, rheumatoid factor, antibodies to the cyclic citrullinated peptide, S-reactive protein, proinflammatory cytokines, monocyte-macrophage protein, vascular endothelial factor, and cell cycle analysis). The obtained data were processed with Statistics 7.0 software. The results were considered to be statistically reliable at р &lt; 0.05. Results. Hyper production of proinflammatory cytokines was marked in sick patients compared with healthy ones. The analysis of peripheral blood lymphocytes in patients showed their excess in comparison to healthy people. The assessment of lymphocytes ability for blast transformation defined the lymphocytes activation with the growth of cells at apoptosis stage (G1-phase); with the decrease in the proportion of resting cells (GO-phase) in patients, the activation coefficient was significantly growing. More apoptosis activation markers were found in the group of RA patients. Changes in apoptosis were revealed with the decreased proportion of lymphocytes in unstimulated cultures of patients; at the same time, the amount of cells in apoptosis increased four times in the examined patients compared to the healthy ones. Conclusions. In patients with RA and AS, changes of the factors of the immune system wee noted as the amount of pro-inflammatory cytokines IL—1β, IL-6, TNF—α and the concentration of MSR-1, VEGF, SPB, RF increased. The enhancement of cellular apoptosis is due to the increase of the apoptosis inducer — CD95+9(FaS) lymphocytes, TNF- α, the growth of cells at pre-synthetic stage of apoptosis G1-phase and the activation coefficient.

Impact of yoga based mind-body intervention on systemic inflammatory markers and co-morbid depression in active Rheumatoid arthritis patients: A randomized controlled trial. Restor Neurol Neurosci. 2019;37(1):41-59

Rheumatoid Arthritis (RA), an autoimmune disorder develops pain, synovitis, cartilage degradation and bony erosion along with showing the symptoms of depression among the patients. Recent studies have shown that mind body interventions like yoga is effective improving quality of life and depression among patients in such autoimmune conditions. This study has shown improvement of systematic inflammatory markers and co-morbid depression among the yoga group of the active RA patients.

Aerobic exercise and fatigue indices in rheumatoid arthritis patients in the health resort care setting

To evaluate the effectiveness of aerobic exercise (walking) to reduce fatigue in RA patients in the health resort setting. The study involved 102 female patients with RA (age 54.38±11.3 years, body mass index 20-29 kg/m2, DAS28-ESR ≤3.2, with severe fatigue of VAS ≥50) who received 21 days of health resort treatment. The health-improving and therapeutic complex includes dosed physical activity, aerobic exercises (walking). Visual analog scale (VAS0-100) and Bristol Rheumatoid Arthritis Fatigue Scale-Numerical Rating Scale (BRAF-NRS V2) were used to assess fatigue, and the 50-meter walking test was used to evaluate the functional status of patients. A correlation between walking duration and the number of steps at a distance of 50 m (p<0.001) as well as between these indices and fatigue (p<0.001) was shown. A positive effect of a standard three-week medical rehabilitation program for patients with RA on fatigue NRS severity (p=0.003) and NRS effect (p=0.037), as well as on patients' functional status (reduced time spent on the 50-meter test, p=0.01) was demonstrated. When comparing groups of RA patients with low (group 1, <5000-6000 steps per day) and optimal (group 2, ≥7000-8000 steps per day) aerobic exercise, positive results were noted in the short term (at 3 weeks) (p<0.001). Aerobic exercise is a promising intervention for treating fatigue in rheumatoid arthritis patients. Medical rehabilitation in a resort setting is the best starting point to encourage performing regular physical activity, as well as the best way to develop exercise programs tailored to rheumatoid arthritis patients.

Disease knowledge and preferences for disclosure of information in patients with rheumatoid arthritis

Objectives: To verify the level of knowledge about rheumatoid arthritis (RA) and the patient’s preferences for disclosure of information by the physician in patients with RA, we compared with a control group of patients without RA.&#x0D; Methods: We evaluated 30 patients diagnosed with RA, according to the ACR criteria, and 30 patients with other diseases pared for age, gender, level of education, and disease duration followed in an Out-Patient Service. Clinical-demographic data as age, gender, level of education, and disease duration were obtained from both groups. We applied questionnaires to evaluate the level of knowledge about RA (10 questions) with answers yes or no, and the patient’s preference for disclosure of information by the physician (4 questions) in a Likert scale from a) strongly agree to e) strongly disagree to both groups. The questionnaires were validated for Portuguese by the method of translation and re-translation. The Ethical Committee at the Pontifical Catholic University approved the study, and we obtained informed consent from all patients. When appropriat-ed, statistical analysis of the data included the chi-square test and student’s t-test. The significance level was 0.05.&#x0D; Results: Over 30 patients with RA, 27 patients (90%) were women, the mean age was 50.8 years old, with a mean of 3.03 years on school, and mean disease duration of 10.6 years. The knowledge about RA as a mean reached 5.36 points in 10 as a correct answer in RA patients and 5.13 in controls. Concerning the patient’s preference for disclosure of information by the physician, the results varied between 23.3% and 90% in the answers strongly agree or agree in the group of RA patients and 6.6% to 90% in controls. In a specific question about "patients with RA should not play a role in managing their disease because the physician is the one in charge," 56.6% of RA patients agreed, and 46,6% of controls too. Only one question about patient’s preference for disclosure of information by the physician “When there is more than one way to treat a problem, I should be told about each one” there was a trend to differ between the controls and the RA patients (p=0.06). The analysis of the results showed no statistical difference in answers to the questionnaires between RA patients and controls.&#x0D; Conclusion: Our results showed that RA patients, compared to control patients with other non-rheumatic diseases, do not show differences to the level of knowledge about rheumatoid arthritis (RA) and the patient’s preferences for disclosure of information by the physician.&#x0D;

Early Myocardial Changes in Patients with Rheumatoid Arthritis without Known Cardiovascular Diseases-A Comprehensive Cardiac Magnetic Resonance Study.

Clinically silent cardiac disease is frequently observed in rheumatoid arthritis (RA), and cardiovascular complications are the leading cause of mortality in RA. We sought to evaluate the myocardium of young RA patients without known cardiac disease using cardiac magnetic resonance (CMR), including T1/T2 mapping sequences. Eighteen RA patients (median age 41 years, 83% females) mainly with low disease activity or in remission and without any known cardiovascular disease were prospectively included to undergo CMR. A control group consisted of 10 sex- and age-matched patients without RA or any known structural cardiovascular disease. Heart chambers size and left/right ventricular systolic function were similar in patients with RA and controls. Signs of myocardial oedema were present in up to 39% of RA patients, including T2 time above cut-off value in 7 patients (39%) in comparison to none of the controls (p = 0.003) and T2 signal intensity ratio above the cut-off value in 6 patients (33%) and in none of the controls (p = 0.06). Extracellular volume was similar in both groups signifying a lack of diffuse fibrosis in studied group of RA patients. There were also no signs of late gadolinium enhancement (LGE) in either group except for one patient with RA who was found to have prior silent myocardial infarction. No correlation was found between markers of disease severity and markers of oedema observed on CMR in patients with RA. Nevertheless, patients with increased T2 time (≥50 ms) were more likely to have X-ray erosions (p = 0.02) and a longer duration between symptom onset and diagnosis (p = 0.02). Finally, there were no significant arrhythmias on 24-h ECG Holter monitoring in RA patients. CMR features of myocardial oedema without signs of myocardial fibrosis were found in 39% of young RA patients without known heart disease or cardiac symptoms. Presence of myocardial oedema was associated with X-ray erosions and a longer duration between symptom onset and diagnosis. The clinical significance of the observed early myocardial changes accompanying RA requires additional studies.

Investigation of asymptomatic intestinal inflammation in ankylosing spondylitis by fecal calprotectin

Background and Study AimsThis study aimed to investigate the prevalence of intestinal inflammation in patients with ankylosing spondylitis (AS) by assessing fecal calprotectin (FC) levels and comparing them with those in patients with rheumatoid arthritis (RA) and non-inflammatory rheumatic diseases. Our secondary aim was to correlate FC levels with antirheumatic treatment, nonsteroidal anti-inflammatory drug (NSAID) usage, and disease activity measures. Patients and MethodsThis cross-sectional study included 97 patients with AS fulfilling the modified New York criteria, 48 patients with RA fulfilling the American College of Rheumatology criteria, and 49 patients with non-inflammatory rheumatic diseases. All patients were questioned about intestinal complaints, and symptomatic patients were excluded. Disease activity was measured in the AS and RA patient groups. ResultsThe AS group had a significantly higher FC test positivity rate than the RA group (p = 0.016). Furthermore, the AS group had FC levels that were negatively correlated with disease duration (p = 0.04). FC levels were not correlated with any disease activity index, erythrocyte sedimentation rate, C-reactive protein, uveitis, or peripheral arthritis. Patients with AS who used NSAIDs had significantly higher FC levels than nonusers (p = 0.001). ConclusionsThis study revealed that 11% of patients with AS without intestinal complaints had elevated FC levels. FC levels were not correlated with disease activity in AS. Subclinical intestinal inflammation was higher in the early stages of AS. The AS group had a significantly higher FC test positivity than the RA group. In the AS group, NSAID users had significantly higher FC levels than nonusers; thus, no statistically significant difference was observed between biological agent users and nonusers.

Plasma fibrinogen, d-dimer, and fibrin degradation product as biomarkers of rheumatoid arthritis

This study aimed to assess the association of coagulation-related indicators such as plasma fibrinogen (FIB), d-dimer, and fibrin degradation product (FDP) in rheumatoid arthritis (RA) with the disease activity. Data from 105 RA patients and 102 age- and gender-matched healthy controls were collected in the retrospective study. Disease activity score in 28 joints based on C-reactive protein (DAS28-CRP) was used to divide RA patients into low activity group (DAS28-CRP ≤ 2.7) and active group (DAS28-CRP > 2.7). Receiver operating characteristic (ROC) curve was applied to determine area under the curve (AUC). The association between plasma FIB, d-dimer, and FDP and DAS28-CRP was evaluated by spearman correlation. Logistical regression analysis was used to identify the independent variables associated with RA disease activity. RA patients showed higher levels of plasma FIB, d-dimer, and FDP than the controls (P < 0.01). Plasma FIB, d-dimer, and FDP were also increased in active groups of RA patients than those in inactive groups (P < 0.001). ROC curve analyses revealed that the AUC of d-dimer was higher than erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF), and that of FDP was higher than RF in RA patients. In addition, the optimal cut-off value of plasma FIB, d-dimer, and FDP for RA diagnosis was 286 mg/dL, 470 μg/L, and 1.45 mg/L, respectively. Spearman analysis showed that plasma FIB, d-dimer, and FDP were positively related with DAS28-CRP (P < 0.001) in RA patients. Logistical regression analysis showed that d-dimer (odds ratio 2.862, 95% confidence interval 1.851–5.426, P < 0.001) was an independent variable associated with RA disease activity. FIB, d-dimer, and FDP were increased in RA patients and positively correlated with the disease activity of RA. d-dimer may act as a novel inflammatory indice for indicating disease activity in RA patients.

Sexual dysfunction in women with rheumatic diseases

Objective: to assess sexual function in female patients with rheumatoid arthritis (RA) and fibromyalgia (FM) and to identify the main risk factors of sexual dysfunction (SD).Patients and methods. 60 patients with FM (mean age 44.2±10.1 years) – Group 1; 69 patients with RA (mean age 45.0±9.6 years) – Group 2; and 100 healthy women controls (mean age 45.1±11.8 years) – Group 3 were enrolled in the study. Medical history, severity of pain at rest and during movement by visual analog scale (VAS), and anxiety and depression symptoms by hospital anxiety and depression scale (HADS) were assessed. Sexual function was evaluated by «Female Sexual Function index (FSFI)».Results and discussion. The overall sexual function score in Group 1 (12.7±9.0) was almost twice lower than in the control group (23.55±8.24, p&lt;0.001) and in Group 2 (20.9±11, p&lt;0.001). There was no difference between RA patients group and control group, where the average score for each of the scales was above 3 (with the exception of the «desire» scale). In FM patients all scales were below 3 points, which indicated significant SD, score on the «orgasm» scale was the lowest (1.8±0.9), and score on «absence of sexual pain» scale was the highest (2.6±1.8). SD in patients with FM was significantly driven by affective disorders presenting with anxiety and depression. Inflammatory activity and severity of pain by VAS were strongly associated with SD in RA group. The divorced person status was associated with the development of SD, regardless of nosological diagnosis.Conclusion. RA and FM have a negative impact on women's sexual function. The inflammatory disease activity is the main driver of SD in RA patients while affective disorders promote SD in FM patients.

Tumour necrosis factor inhibitors reduce aortic stiffness progression in patients with long-standing rheumatoid arthritis

BackgroundAortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi).MethodsAoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study.ResultsWe included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p<0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (−1.02%, p<0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors.ConclusionLong-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.

Angiotensin-Inhibiting Drugs Do Not Impact Disease Activity in Patients with Rheumatoid Arthritis: A Retrospective Cross-Sectional Study.

Objectives: Besides their proven effectivity in decreasing the risk of cardiovascular events, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARBs) are likely to possess anti-inflammatory properties as well. This study aims to investigate whether the use of ACEi and ARBs additionally lowers disease activity in patients with rheumatoid arthritis (RA). Methods: In this cross-sectional study, we used ARBs or ACEi to study RA patients who had at least one DAS28-CRP measurement during a one-year period. A control group of RA patients without ACEi/ARBs was randomly selected. The primary outcome was the difference between the DAS28-CRP scores of ACEi/ARBs users and controls. The secondary outcomes were the differences between administered dosages of csDMARDs and bDMARDs for users and controls, respectively; these were expressed in defined daily dose (DDD). Confounders were included in the multiple regression analyses. Results: A total of 584 ACEi/ARBs users and 552 controls were finally examined. Multiple linear regression analyses showed no association between the use of ACEi or ARBs and the DAS28-CRP scores (ACEi factor 1.00, 95% CI 0.94–1.06; ARBs 1.02, 95% CI 0.96–1.09), nor with the dosage of csDMARDs (ACEi 0.97, 95% CI 0.89–1.07; ARBs 0.99, 95% CI 0.90–1.10). Furthermore, the use of ACEi was not associated with reduced dosages of bDMARDs (OR 1.14, 95% CI 0.79–1.64), whereas ARBs users tended to use less bDMARDs (1.46, 95% CI 0.98–2.18, p = 0.06). Conclusion: In this study, the use of either ACEi or ARBs in RA patients had no impact on disease activity as measured by the DAS28-CRP. A trend towards lower bDMARD dosages was observed in ARBs users, but the significance of this finding is still unclear.

P144 What is the role of musculoskeletal ultrasound in assessing disease activity of RA in pregnancy?

Abstract Background/Aims In rheumatoid arthritis (RA), musculoskeletal ultrasound (MSK-US) has greater sensitivity for the detection of active disease than clinical assessment using the DAS28 score, which is prone to false elevation by a spuriously high tender joint count (TJC) and/or visual analogue score (VAS) from non-RA causes. Thus, DAS28 may correlate poorly with MSK-US findings. In pregnancy, standardised disease activity of RA comprises calculation of the modified DAS28(3)CRP score, with removal of the VAS and ESR, both of which are confounded by pregnancy, and replacement with CRP; however, it is unknown whether non-specific musculoskeletal pain and/or peripheral oedema in (especially late) pregnancy might contribute to the TJC or swollen joint count (SJC) respectively and thus render this adapted score less reliable. Therefore, we conducted this study of pregnant RA patients and controls to assess the ability of the DAS28(3)CRP to detect disease activity compared with MSK-US. Methods Pregnant RA patients were recruited from the UCLH obstetric rheumatology clinic from September 2018 to March 2020. Patients underwent clinical assessment with DAS28(3)CRP and MSK-US longitudinally through pregnancy/post-partum. A control group of age-matched non-pregnant female RA patients was recruited from general rheumatology clinics and had equivalent assessments. MSK-US was undertaken using a Logiq S8. The standard protocol comprised 22-joint assessment of hands (dorsal longitudinal and transverse views of wrists, metacarpophalangeal and proximal interphalangeal joints). Quantification of Power Doppler (PD) signal was made as per the Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) US definitions. PD scores were calculated as mean scores of all joints scanned. Statistical correlations were performed in SPSS using Spearman’s rank coefficient as data were non-normally distributed. Results A total of 45 MSK-US scans of pregnant/postpartum RA patients (N = 24, mean age 34.5+-3.6) were performed and compared to a control group of non-pregnant RA patients, who were scanned once each (N = 18, mean age 32.3+-5.2; p = 0.12). In the second (T2) and third trimester (T3) and the postpartum (PP), there was a significant positive correlation between DAS28(3)CRP and PD score (T2, ρ = 0.87 (p &amp;lt; 0.01); T3, ρ = 0.76 (p &amp;lt; 0.01); PP, ρ = 0.68 (p = 0.03)). Interestingly, each of these were stronger correlations than the equivalent comparison in non-pregnant RA patients (ρ = 0.51 (p = 0.03)). TJC also significantly positively correlated with PD score in each trimester of pregnancy and postpartum, but not in non-pregnant patients; difference between correlation coefficients was statistically significant for each trimester (T1, p &amp;lt; 0.01; T2, p = 0.05; T3, p = 0.05). Conclusion Interestingly, we found that that DAS28(3)CRP correlates better with PD signal on MSK-US in pregnancy than in non-pregnancy. Specifically, there was significantly better correlation of the TJC with PD score. It is unclear why non-inflammatory contributors to the TJC may be less prominent in pregnancy and further investigation is warranted. Disclosure C. Raine: Grants/research support; C.R. has received research funding from UCB. J. Manson: None. C. Ciurtin: None. I. Giles: Grants/research support; IG has received an unrestricted educational grant, speaker's fees and travel fees from UCB.

P143 The effect of JAK inhibition on the metabolome of neutrophils from patients with rheumatoid arthritis

Abstract Background/Aims Janus kinase inhibitors (JAKi) including baricitinib and tofacitinib target the JAK/STAT pathway and are clinically effective in treating rheumatoid arthritis (RA). Neutrophils play a key role in the pathophysiology of RA and their function is directly affected by these drugs as shown by clinical trials of JAKi which report increased infection rates and transient neutropenia during therapy. The aim of this work is to determine difference in the metabolome of neutrophils from healthy controls and patients with RA, and the effect of JAKi on the metabolome of healthy and RA neutrophils. Methods Neutrophils were isolated from healthy controls (HC) (n = 10) and patients with RA (n = 10 DMARD-naïve, n = 10 Biologics-naive) and pre-incubated with baricitinib, tofacitinib or a pan-JAK inhibitor (all 200ng/mL) for 2h before snap-freezing. Metabolites were extracted by 50:50 v/v AcN:H2O and analysed by 1H NMR spectroscopy using a 700 MHz Avance IIIHD Bruker NMR spectrometer equipped with a TCI cryoprobe. Chenomx, Bruker TopSpin and tameNMR software were used to identify metabolites and process spectra. Statistical analysis and machine learning models were implemented using R and the Mixomics package. Pathway analysis was carried out using Ingenuity (IPA). ROS production in response to 15 min fMLP stimulation was measured using DHR-123 and flow cytometry. Results At 0h, changes in levels of NADP+, NADPH and hypoxanthine in RA neutrophils indicated increased production of ROS via NADPH oxidase and xanthine oxidase compared to HC. Lower levels of glucose and increased levels of lactic acid also suggested increased glycolysis in RA neutrophils compared to HC. However after 2h incubation with JAKi, a difference in the response to these drugs was observed. 80 metabolites were higher in RA neutrophils compared to HC following 2h JAKi treatment. IPA analysis revealed the metabolites higher in RA neutrophils were involved in NAD biosynthesis, NAD phosphorylation/dephosphorylation, amino acid synthesis and transport, and carbohydrate metabolism. Changes in the levels of NADP+, NADPH and hypoxanthine in RA neutrophils indicate that JAKi inhibit ROS production. We therefore confirmed experimentally that JAKi inhibit ROS production in response to fMLP (p &amp;lt; 0.05). IPA also predicted altered neutrophil cell functions including cell death and cell-to-cell signalling. We previously showed that JAKi did not affect the constitutive rate of neutrophil apoptosis, however JAKi significantly inhibit the delay in apoptosis induced by GM-CSF (p &amp;lt; 0.05). No significant difference in the metabolome was observed when comparing tofacinib-treatment and baricitinib-treatment in either the HC or RA patient group. Conclusion The metabolome of RA and HC neutrophils is different at baseline. JAKi alter the levels of intracellular metabolites involved in neutrophil activation and ROS production in RA. This may explain, in part, the efficacy of JAKi in decreasing disease activity and joint damage in RA. Disclosure M. Fresneda Alarcon: None. R. Grosman: None. S. Chokesuwattanaskul: None. M. Phelan: None. H. Wright: None.

Does the Course of Disease Influence the Development of Fatigue in Rheumatoid Arthritis Patients?

Abstract Patients with rheumatoid arthritis (RA) typically have many permanently inflamed joints. The inflammation inside the body can lead to general physical weakness, exhaustion, and drowsiness. This feeling of extreme tiredness is also called “fatigue”. Some people find this to be the worst symptom of the disease. However, the clinical significance of fatigue and its pathogenesis have not been recognised. This study aimed to determine the development of fatigue depending on activity and aggressiveness of RA. To achieve the goal, patients were interviewed and indicators of disease activity and aggressiveness were determined: rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulins IgA RF, IgM RF, IgG RF and anti-carbamylated protein antibodies (anti-CarP). Based on the results of the survey, RA patients were divided into two groups — with and without fatigue. In the group of RA patients with fatigue, statistically more often an increase in IgA RF, IgM RF, and IgG RF levels was observed in those with elevated RF level, higher IgM RF and IgG RF levels were associated with increase in IgA RF level, and increase in the IgG RF and anti-CarP levels with elevation in the IgM RF level. A higher IgG RF level contributed to a higher anti-CarP level increase. Significant differences in the levels of clinical and laboratory inflammatory markers were not observed between the RA patients with and without fatigue. The obtained data suggest that the aggressive course of RA, more than inflammation, may contribute to the development of fatigue in RA patients.

Left ventricular hypertrophy predicts poorer cardiovascular outcome in normotensive normoglycemic patients with rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) develop early changes in left ventricular (LV) geometry and experience cardiovascular events in excess than in the general population. This study was designed to assess prevalence, predictors and prognostic role of LV hypertrophy (LVH) in a selected group of RA patients with normal blood pressure and glycemia who should be at low risk for LVH. We prospectively analyzed 241 normotensive normoglycemic RA patients (mean age 53±12years, 61% women) involved in a primary prevention program for cardiovascular diseases who were followed-up for 40 (24-56) months. LVH was detected by echocardiography and defined as LV mass ≥49.2g/m2.7 for men and ≥46.7g/m2.7 for women. Primary outcome was a composite of cardiovascular death/hospitalization. LVH was detected in 39 patients (16%). Older age (>53years), greater body mass index (BMI>25kg/m2 ), longer duration of RA disease, anti-cyclic citrullinated peptide antibody (ACPA) positivity and concentric LV geometry were the variables associated with LVH. During the follow-up, a cardiovascular event occurred in 12 of 39 (31%) patients with LVH and in 22 of 202 (11%; P<.001) patients without LVH. LVH independently predicted cardiovascular events (hazards ratio 3.28 [95% CI 1.03-9.20], P=.03) at Cox regression analysis together with C-reactive protein and ACPA positivity. Nearly one-sixth of normotensive normoglycemic RA patients analyzed in a primary prevention program for cardiovascular diseases has LVH which is associated with obesity and older age, and strongly predicts cardiovascular event in these subjects.

Utility of pulmonary ultrasound to identify interstitial lung disease in patients with rheumatoid arthritis.

To analyze the diagnostic utility of lung ultrasound (US) to detect interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients comparing with high-resolution computed tomography (HRCT) PATIENTS AND METHODS: We performed a cross-sectional, observational study in patients with RA-ILD (cases) controlled with a group of RA patients without ILD (controls) paired by sex, age, and time of disease evolution. Patients were assessed using HRCT, PFT, and US. The main variables were B-line number, evaluation of the lung-US score already described, pleural irregularities, and A pattern US lost. ROC curve analysis was performed to establish the cut-off point of the US B-lines number for detecting the presence of significant RA-ILD in relation to HRCT, and logistic regression analysis was performed to identify the intercostal spaces. Seventy-one patients were included, 35 (49.2%) with ILD-RA and 36 (50.8%) RA controls. Regarding US score, we found that the detection of 5.5 lines in a reduced score of 8 intercostal spaces had a sensitivity = 62.2%, specificity = 91.3%, PPV = 88.4%, and NPV = 69.5%. In multivariate analysis, the intercostal spaces which showed independent association with ILD were 3rd right anterior axillary space (OR [IC 95%] 19.0 [1.3-27.5]), 8th right posterior axillary space (OR [IC 95%] 0.04 [0.0-0.6]), 8th right subscapular space (OR [IC 95%] 16.5 [1.8-45.5]), 9th right paravertebral space (OR [IC 95%] 7.11 [1.0-37.1]), and 2nd left clavicular middle space (OR [IC 95%] 21.9 [1.26-37.8]). Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. A 8-space reduced score showed a similar total predictive capacity than 72-space score. Key Points • Lung ultrasound could be a useful tool for ILD diagnosis associated with rheumatoid arthritis. • The 72-space evaluation is highly sensitive, whereas a simplified score enables a more specific and faster diagnosis. • The number of B lines is correlated with DLCO, ACPA, inflammatory activity, and physical function.

Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (&lt;1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p&lt;0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p&lt;0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was &gt;50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1β, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

Аssessment of osteoporosis and occurrence of vertebral fractures in postmenopausal patients with rheumatoid arthritis treated with small doses of glucocorticoids

Osteoporosis (OP) is a serious extracorporeal manifestation that occurs in patients with rheumatoid arthritis (RA). One of the risk factors is long-term use of glucocorticoids (GC). Osteoporosis together with the increased risk of vertebral (VF) and non-vertebral fractures (non-VF) in particular has a negative impact on quality of life in patients with rheumatoid arthritis. The aim of the study was to detect the occurrence of OP and VF in postmenopausal patients with RA and their association with long-term use of small doses of glucocorticoids. Material and methods: A total of 46 patients were analyzed. All respondents underwent imaging for osteoporosis evaluation with a DXA scanner (Lunar iDXA, GE) and VF with incorporated Vertebral Fracture Assessment (VFA). Results: The values of bone mineral densities (BMD) were significantly smaller in the group that received glucocorticoids. According to VFA, 37,0% of patients were registered to have a fracture of middle degree, a mild fracture was registered in 19.6% of patients, and severe fractures were registered in 3 patients (6.5%). Conclusion: In postmenopausal patients with RA receiving GC therapy, a more common occurrence of osteoporosis and vertebral fractures was reported compared with the remaining group of RA patients. All patients with RA in menopause need to be screened for timely detection and treatment of osteoporosis and prevention of its complications.

Is rheumatoid arthritis a risk factor for acute coronary syndrome also among individuals at elevated risk, such as individuals presenting with acute chest pain?

BackgroundPatients with rheumatoid arthritis (RA) are, on average, at increased risk of acute coronary syndrome (ACS) compared to the general population, but it remains unknown whether RA remains an ACS...