Rheumatoid Arthritis Participants Research Articles

Ambulatory Blood Pressure in Patients With Rheumatoid Arthritis: Association With Immune Activation.

The prevalence of hypertension, a major cardiovascular risk factor, is increased in patients with rheumatoid arthritis (RA) and may be driven by immune activation. The purpose of this study was to determine if ambulatory 24-hour blood pressure (BP) is elevated in RA vs control participants and whether it is associated with immune activation. We conducted a cross-sectional study of 46 patients with RA and 23 control participants. Participants wore an ambulatory BP monitor that obtained diurnal BP every 15-30 minutes and nocturnal BP every 30 minutes. Inflammatory mediators in plasma were measured using an inflammation proteomics panel. Differences in BP measurements were assessed by Mann-Whitney U test, and association with inflammatory mediators was assessed by Spearman correlation. Patients with RA and control participants had similar office BP, but median ambulatory systolic BP (SBP) measurements (24-hour [RA 121 mmHg vs control 116 mmHg; P = 0.01], diurnal [RA 128 mmHg vs control 120 mmHg; P = 0.003], and nocturnal [RA 112 mmHg vs control 103 mmHg; P = 0.002]) were higher in patients with RA. Patients with RA also had higher nocturnal diastolic BP (DBP; RA 63 mmHg vs control 57 mmHg; P = 0.02), but other DBP measurements were similar. Nocturnal BP dipping was less in patients with RA (12%) compared to control participants (16%; P = 0.02). In patients with RA, higher 24-hour and nocturnal SBPs and less nocturnal dipping were strongly correlated with a wide range of inflammatory mediators. Despite similar office measurements, 24-hour and nocturnal SBP measurements were higher in patients with RA than in control participants and were strongly associated with inflammation.

Serum Mac-2 binding protein glycosylation isomer and galectin-3 levels in adult-onset Still's disease and their association with cytokines.

Autoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still's disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD. We recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks. Significant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively). Although both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades.

Long-term effectiveness of a lifestyle intervention for rheumatoid arthritis and osteoarthritis: 1-year follow-up of the ‘Plants for Joints’ randomised clinical trial

ObjectivesIn two randomised controlled trials, the Plants for Joints (PFJ) multidisciplinary lifestyle intervention reduced signs and symptoms of rheumatoid arthritis (RA), or metabolic syndrome-associated hip or knee osteoarthritis (MSOA) compared...

Digital health technologies and machine learning augment patient reported outcomes to remotely characterise rheumatoid arthritis

Digital measures of health status captured during daily life could greatly augment current in-clinic assessments for rheumatoid arthritis (RA), to enable better assessment of disease progression and impact. This work presents results from weaRAble-PRO, a 14-day observational study, which aimed to investigate how digital health technologies (DHT), such as smartphones and wearables, could augment patient reported outcomes (PRO) to determine RA status and severity in a study of 30 moderate-to-severe RA patients, compared to 30 matched healthy controls (HC). Sensor-based measures of health status, mobility, dexterity, fatigue, and other RA specific symptoms were extracted from daily iPhone guided tests (GT), as well as actigraphy and heart rate sensor data, which was passively recorded from patients’ Apple smartwatch continuously over the study duration. We subsequently developed a machine learning (ML) framework to distinguish RA status and to estimate RA severity. It was found that daily wearable sensor-outcomes robustly distinguished RA from HC participants (F1, 0.807). Furthermore, by day 7 of the study (half-way), a sufficient volume of data had been collected to reliably capture the characteristics of RA participants. In addition, we observed that the detection of RA severity levels could be improved by augmenting standard patient reported outcomes with sensor-based features (F1, 0.833) in comparison to using PRO assessments alone (F1, 0.759), and that the combination of modalities could reliability measure continuous RA severity, as determined by the clinician-assessed RAPID-3 score at baseline (r2, 0.692; RMSE, 1.33). The ability to measure the impact of the disease during daily life—through objective and remote digital outcomes—paves the way forward to enable the development of more patient-centric and personalised measurements for use in RA clinical trials.

Anti-Inflammatory Effect of High-Density Lipoprotein Blunted by Delivery of Altered MicroRNA Cargo in Patients With Rheumatoid Arthritis.

High-density lipoprotein (HDL) has well-characterized anti-atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in rheumatoid arthritis (RA) is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study's purpose was to determine if HDL-miRNA cargo is altered and affects inflammation in RA. HDL-microRNAs were characterized in 30 RA and 30 control participants by next generation sequencing and quantitative polymerase chain reaction. The most abundant differentially expressed miRNA was evaluated further. The function of miR-1246 was assessed by miRNA mimics, antagomiRs, small interfering RNA knockdown, and luciferase assays. Monocyte-derived macrophages were treated with miR-1246-loaded HDL and unmodified HDL from RA and control participants to measure delivery of miR-1246 and its effect on interleukin-6 (IL-6). The most abundant miRNA on HDL was miR-1246; it was significantly enriched two-fold on HDL from RA versus control participants. HDL-mediated miR-1246 delivery to macrophages significantly increased IL6 expression 43-fold. miR-1246 delivery significantly decreased DUSP3 1.5-fold and DUSP3 small interfering RNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR-1246. Unmodified HDL from RA delivered 1.6-fold more miR-1246 versus control participant HDL. Unmodified HDL from both RA and control participants attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4-fold higher after RA versus control HDL treatment. HDL-miR-1246 was increased in RA versus control participants and delivery of miR-1246 to macrophages increased IL-6 expression by targeting DUSP3. The altered HDL-miRNA cargo in RA blunted HDL's anti-inflammatory effect.

Rheumatoid arthritis, quantitative parenchymal lung features, and mortality among smokers.

There have been limited investigations of the prevalence and mortality impact of quantitative computed tomography (QCT) parenchymal lung features in rheumatoid arthritis (RA). We examined the cross-sectional prevalence and mortality associations of QCT features, comparing RA and non-RA participants. We identified participants with and without RA in COPDGene, a multicentre cohort study of current or former smokers. Using a k-nearest neighbor quantifier, high resolution CT chest scans were scored for percentage of normal lung, interstitial changes, and emphysema. We examined associations between QCT features and RA using multivariable linear regression. After dichotomizing participants at the 75th percentile for each QCT feature among non-RA participants, we investigated mortality associations by RA/non-RA status and quartile 4 vs quartiles 1-3 of QCT features using Cox regression. We assessed for statistical interactions between RA and QCT features. We identified 82 RA cases and 8820 non-RA comparators. In multivariable linear regression, RA was associated with higher percentage of interstitial changes (β = 1.7 ± 0.5, p= 0.0008) but not emphysema (β = 1.3 ± 1.7, p= 0.44). Participants with RA and >75th percentile of emphysema had significantly higher mortality than non-RA participants (HR 5.86, 95%CI 3.75-9.13) as well as RA participants (HR 5.56, 95%CI 2.71-11.38) with ≤75th percentile of emphysema. There were statistical interactions between RA and emphysema for mortality (multiplicative p= 0.014; attributable proportion 0.53, 95%CI 0.30-0.70). Using machine learning-derived QCT data in a cohort of smokers, RA was associated with higher percentage of interstitial changes. The combination of RA and emphysema conferred >5-fold higher mortality.

Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis

Molecular markers of autoimmunity, such as antibodies to citrullinated protein antigens (ACPA), are detectable prior to inflammatory arthritis (IA) in rheumatoid arthritis (RA) and may define a state that is ‘at-risk’ for future RA. Here we present a cross-sectional comparative analysis among three groups that include ACPA positive individuals without IA (At-Risk), ACPA negative individuals and individuals with early, ACPA positive clinical RA (Early RA). Differential methylation analysis among the groups identifies non-specific dysregulation in peripheral B, memory and naïve T cells in At-Risk participants, with more specific immunological pathway abnormalities in Early RA. Tetramer studies show increased abundance of T cells recognizing citrullinated (cit) epitopes in At-Risk participants, including expansion of T cells reactive to citrullinated cartilage intermediate layer protein I (cit-CILP); these T cells have Th1, Th17, and T stem cell memory-like phenotypes. Antibody-antigen array analyses show that antibodies targeting cit-clusterin, cit-fibrinogen and cit-histone H4 are elevated in At-Risk and Early RA participants, with the highest levels of antibodies detected in those with Early RA. These findings indicate that an ACPA positive at-risk state is associated with multifaceted immune dysregulation that may represent a potential opportunity for targeted intervention.

The Influence of Rheumatoid Arthritis and Osteoarthritis on the Occurrence of Arterial Hypertension: An 8-Year Prospective Clinical Observational Cohort Study.

Rheumatoid arthritis (RA) increases the risk of cardiovascular mortality and morbidity, including a 50-60% increased risk of cardiovascular disease (CVD). Arterial hypertension (HT) is considered the major contributing risk factor for CVD development in RA patients. In this investigation, we compared the incidence and prevalence of HT between RA and osteoarthritis (OA) and the influence of HT on CVD development in CVD-naive patients in both groups. This was a prospective clinical cohort investigation with an 8-year follow-up period. A total of 201 participants, 124 with RA (investigation group) and 77 with OA (control group), without diagnosed CVD or symptomatic heart failure were included. After selection according to inclusion and exclusion criteria, both groups underwent initial and final visits, and the investigation group underwent annual visits to assess disease activity. Case report forms were completed for each visit. The obtained data were analyzed by a statistician. No difference in the incidence or prevalence of HT was found between the investigation and control groups. No difference in the prevalence of HT was reported between the study groups and age-standardized data from the general population. The investigation group had a higher incidence of CVD than the control group. RA participants with long-term remission had a marginally lower HT prevalence. Although previous studies reported a higher HT prevalence in RA than in OA and the general population, our findings did not support this. The RA group had a higher incidence of CVD, but it is possible that optimal disease control with long-term remission could reduce HT incidence and prevalence while also having beneficial effects on other cardiovascular risk factors (CV) and, consequently, CVD occurrence.

Circulating Th17/Treg as a promising biomarker for patients with rheumatoid arthritis in indicating comorbidity with atherosclerotic cardiovascular disease.

Immune and inflammatory responses have a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and atherosclerotic cardiovascular disease (ASCVD). This study aims to explore the change of peripheral lymphocytes, especially the absolute and relative changes in peripheral T cells in RA patients with and without ASCVD. The changes in the lymphocyte subsets were assessed to provide a novel insight in diagnosing and preventing ASCVD in patients with RA. A propensity score matching system (1:1) was conducted to perform a matched case-control study with 169 pairs RA-ASCVD and RA participants. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-ASCVD. Multivariate logistic regression analysis demonstrated that Th17 cell absolute, Th17 cell Ratio, Th17/Treg were associated with a significantly higher risk of ASCVD after model adjustment. Then we focused on Th17/Treg, multivariate logistic analyses in tri-sectional Th17/Treg groups showed that the odds of ASCVD is gradually increasing with Th17/Treg rank's rising after model adjustment. Finally, the restricted cubic spline of Th17/Treg and odds ratio of RA-ASCVD was conducted. Interestingly, we found a critical point of Th17/Treg (critical point = 0.2399). Th17/Treg shows a protective role in the odds of ASCVD when Th17/Treg < 0.2399. With smaller Th17/Treg, the protective efficiency is more obvious when Th17/Treg < 0.2399. Our study suggested that increasing absolute and percentage of Th17 cells in the peripheral blood of patients with RA was associated with the development of ASCVD. And Th17/Treg may be a promising biomarker for patients with RA in indicating comorbidity with ASCVD.

Association between skeletal muscle mitochondrial dysfunction and insulin resistance in patients with rheumatoid arthritis: a case–control study

BackgroundInsulin resistance affects a substantial proportion of patients with rheumatoid arthritis (RA). Skeletal muscle mitochondrial dysfunction results in the accumulation of lipid intermediates that interfere with insulin signaling. We therefore sought to determine if lower oxidative phosphorylation and muscle mitochondrial content are associated with insulin resistance in patients with RA.MethodsThis was a cross-sectional prospective study of RA patients. Matsuda index from the glucose tolerance test was used to estimate insulin sensitivity. Mitochondrial content was measured by citrate synthase (CS) activity in snap-frozen muscle samples. Mitochondrial function was measured by using high-resolution respirometry of permeabilized muscle fibers and electron transport chain complex IV enzyme kinetics in isolated mitochondrial subpopulations.ResultsRA participants demonstrated lower insulin sensitivity as measured by the Matsuda index compared to controls [median 3.95 IQR (2.33, 5.64) vs. 7.17 (5.83, 7.75), p = 0.02]. There was lower muscle mitochondrial content among RA vs. controls [median 60 mU/mg IQR (45, 80) vs. 79 mU/mg (65, 97), p = 0.03]. Notably, OxPhos normalized to mitochondrial content was higher among RA vs. controls [mean difference (95% CI) = 0.14 (0.02, 0.26), p = 0.03], indicating a possible compensatory mechanism for lower mitochondrial content or lipid overload. Among RA participants, the activity of muscle CS activity was not correlated with the Matsuda index (ρ = − 0.05, p = 0.84), but it was positively correlated with self-reported (IPAQ) total MET-minutes/week (ρ = 0.44, p = 0.03) and Actigraph-measured time on physical activity (MET rate) (ρ = 0.47, p = 0.03).ConclusionsMitochondrial content and function were not associated with insulin sensitivity among participants with RA. However, our study demonstrates a significant association between muscle mitochondrial content and physical activity level, highlighting the potential for future exercise interventions that enhance mitochondrial efficiency in RA patients.

HYBRID AI MODEL FOR THE DETECTION OF RHEUMATOID ARTHRITIS FROM HAND RADIOGRAPHS

The study aims to develop a computerized hybrid model using artificial intelligence (AI) for the detection of rheumatoid arthritis (RA) from hand radiographs. The objectives of the study include (i) segmentation of proximal interphalangeal (PIP), and metacarpophalangeal (MCP) joints using the deep learning (DL) method, and features are extracted using handcrafted feature extraction technique (ii) classification of RA and non-RA participants is performed using machine learning (ML) techniques. In the proposed study, the hand radiographs are resized to [Formula: see text] pixels and pre-processed using the various image processing techniques such as sharpening, median filtering, and adaptive histogram equalization. The segmentation of the finger joints is carried out using the U-Net model, and the segmented binary image is converted to gray scale image using the subtraction method. The features are extracted using the Harris feature extractor, and classification of the proposed work is performed using Random Forest and Adaboost ML classifiers. The study included 50 RA patients and 50 normal subjects for the evaluation of RA. Data augmentation is performed to increase the number of images for U-Net segmentation technique. For the classification of RA and healthy subjects, the Random Forest classifier obtained an accuracy of 91.25% whereas the Adaboost classifier had an accuracy of 90%. Thus, the hybrid model using a Random Forest classifier can be used as an effective system for the diagnosis of RA.

Cardiometabolic multimorbidity may identify a more severe subset of rheumatoid arthritis, results from a “real-life” study

This "real-life" cross-sectional study has been designed to describe disease features of rheumatoid arthritis (RA) participants affected by cardiometabolic multimorbidity than those without. Our purpose was also the identification of possible associations between these cardiometabolic diseases and RA clinical characteristics. Consecutive RA participants with and without cardiometabolic multimorbidity were assessed and their clinical characteristics were recorded. Participants were grouped and compared by the presence or not of cardiometabolic multimorbidity (defined as ≥ 2 out of 3 cardiovascular risk factors including hypertension, dyslipidemia, and type 2 diabetes). The possible influence of cardiometabolic multimorbidity on RA features of poor prognosis was assessed. The positivity of anti-citrullinated protein antibodies, presence of extra-articular manifestations, lack of clinical remission, and biologic Disease-Modifying anti-Rheumatic Drugs (bDMARDs) failure were considered as RA features of poor prognosis. In the present evaluation, 757 consecutive RA participants were evaluated. Among them, 13.5% showed cardiometabolic multimorbidity. These were older (P < .001) and characterized by a longer disease duration (P = .023). They were more often affected by extra-articular manifestations (P = .029) and frequently displayed smoking habit (P = .003). A lower percentage of these patients was in clinical remission (P = .048), and they showed a more frequent history of bDMARD failure (P < .001). Regression models showed that cardiometabolic multimorbidity was significantly correlated with RA features of disease severity. They were predictors of anti-citrullinated protein antibodies positivity, of extra-articular manifestations, and of lack of clinical remission, in both univariate and multivariate analyses. Cardiometabolic multimorbidity was significantly associated with a history of bDMARD failure. We described disease features of RA participants with cardiometabolic multimorbidity, identifying a possible more difficult to treat subset, which may need a new management approach to achieve the treatment goal.

Association of Antibodies to Prevotella copri in Anti-Cyclic Citrullinated Peptide-Positive Individuals At Risk of Developing Rheumatoid Arthritis and in Patients With Early or Established Rheumatoid Arthritis.

Prevotella copri (P copri), a gut commensal, has been reported to be an immune-relevant organism in individuals with rheumatoid arthritis (RA). This study sought to evaluate anti-P copri (anti-Pc) antibody responses in our participant cohorts and to determine when in the natural history of RA such responses develop. We analyzed serum levels of immunoglobulin A (IgA) and IgG antibodies from a 27-kd protein of P copri (anti-Pc-p27), an immunogenic P copri protein, in study participants at risk of developing RA, participants who transitioned to RA, participants with early RA (<1 year of disease), and participants with established RA, with comparisons made to their matched controls. We also evaluated anti-Pc-p27 antibody levels in individuals stratified by RA-related autoantibody status. Overall, participants with RA had significantly higher IgA anti-Pc-p27 antibody levels and trended toward higher IgG anti-Pc-p27 antibody levels compared with matched controls. When stratified by early versus established RA, participants with early RA had median IgG anti-Pc-p27 antibody levels that were overall higher, whereas median IgA anti-Pc-p27 antibody levels were statistically significantly higher in participants with established RA compared with their matched controls. In the autoantibody-specific analyses, the at-risk population with anti-cyclic citrullinated peptide (anti-CCP) antibodies, but not rheumatoid factor (RF), trended toward increased levels of IgG anti-Pc-p27. Additionally, RA participants who were seropositive for both CCP and RF had significantly increased levels of IgA anti-Pc-p27 antibodies and trended toward higher levels of IgG anti-Pc-p27 antibodies compared with matched controls. Our findings support a potential etiologic role for P copri in both RA preclinical evolution and the subsequent pathogenesis of synovitis.

Rheumatoid arthritis characteristics and classification of heat and cold patterns–an observational study

IntroductionTraditional Chinese medicine (TCM) has been proven to be an effective complementary therapy in treating rheumatoid arthritis (RA). The cold pattern and the heat pattern were the two main TCM patterns for RA, which is crucial for TCM treatment. The cold pattern is characterized by fear of cold and wind, joint pain with a thin white tongue coating which can be relieved by hot herbs. In contrast, heat pattern patients suffer from severe joint pain with a yellow coating, with red swelling of the skin and high skin temperature which can be relieved by cooling herbs. ObjectiveWe aimed to classify the heat and cold patterns in RA patients with cluster analysis and factor analysis. Moreover, we aimed to explore the association of RA characteristics between these two patterns. Methodsand Design: A cross-sectional observational research method was used, and data was collected on 300 RA patients in Hangzhou in China. Signs and symptoms associated with RA were clustered using SPSS 22.0 software. In addition, factor analysis was also used for the classification. After classification of heat and cold patterns, characteristics and treatment of the RA participants between the two patterns were explored. ResultsRA patients in the study were divided into two categories using cluster analysis. Twenty-two symptoms in the first category were included in the heat pattern of RA patients. After factor analysis, nine principal components were extracted to heat pattern. The component with the highest eigenvalue (2.530) were mainly contributed by shortness of breath, palpitation, heavy limbs, chest tightness and yellow greasy tongue with high factor loading values (0.765, 0.703, 0.504, 0.429 and 0.402, respectively). Ten symptoms in the second category were included in the cold pattern of RA patients. Four principal components were extracted to cold pattern. The component with the highest eigenvalue (2.089) were mainly contributed by joint distension and pain, joint stiffness, fatigue and upset with high factor loading values (0.597, 0.590, 0.491 and 0.481, respectively). Although there were no statistical differences between the levels of rheumatoid factor and anti-cyclic peptide containing citrulline (anti-CCP), the levels of C-reactive protein, platelet count and the disease activity score using 28 joint counts were significantly higher in the heat pattern RA patients compared to the ones in cold pattern. Moreover, heat pattern RA patients were more likely to be prescribed two more disease-modifying anti-rheumatic drugs (DMARDS) combined with Methotrexate (MTX) (70.59% versus 49.72%; P = 0.000). ConclusionsIn conclusion, heat and cold patterns in RA patients could be classified well using cluster analysis and factor analysis. Most of RA patients with heat pattern were active and likely to be prescribed two more DMARDs combined with MTX.

Association between risk, duration and cause of hospitalisations in people with rheumatoid arthritis and multimorbidity in the UK Biobank and Scottish Early Rheumatoid Arthritis (SERA) cohorts: Longitudinal observational study

ObjectivesTo investigate association between presence of multimorbidity in people with established and early rheumatoid arthritis (RA) and risk, duration and cause of hospitalisations. DesignLongitudinal observational study. SettingUK Biobank, population-based cohort recruited between 2006 and 2010, and the Scottish Early Rheumatoid Arthritis (SERA), inception cohort recruited between 2011 and 2015. Both linked to mortality and hospitalisation data. Participants4757 UK Biobank participants self-reporting established RA; 825 SERA participants with early RA meeting the 2010 ACR/EULAR classification criteria. Participants stratified by number of long-term conditions (LTCs) in addition to RA (RA only, RA + 1 LTC and RA + ≥ 2 LTCs) and matched to five non-RA controls. Main outcome measuresNumber and duration of hospitalisations and their causes. Incidence rate ratios (IRR) and 95% confidence intervals (CI) calculated using negative binomial regression models. ResultsParticipants with RA + ≥ 2 LTCs experienced higher hospitalisation rates compared to those with RA alone (UK Biobank: IRR 2.10, 95% CI 1.91 to 2.30; SERA: IRR 1.74, 95% CI 1.23 to 2.48). Total duration of hospitalisation in RA + ≥ 2 LTCs was also higher (UK Biobank: IRR 2.48, 95% CI 2.17 to 2.84; SERA: IRR 1.90, 95% CI 1.07 to 3.38) than with RA alone. Rate and total duration of hospitalisations was higher in UK Biobank RA participants than non-RA controls with equivalent number of LTCs. Hospitalisations for respiratory infection were higher in early RA than established RA and were the commonest cause of hospital admission in early RA. ConclusionsParticipants with established or early RA with multimorbidity experienced a higher rate and duration of hospitalisations than those with RA alone and with non-RA matched controls.

Forearm Muscle Oxidative Capacity And Biomechanical Property Testing As Clinical Tools For Rheumatoid Arthritis

Rheumatoid arthritis (RA) commonly impairs hand and wrist function. RA skeletal muscle is characterized by weakness, sarcopenia, and altered oxidative metabolism; however, clinical tools for assessment of RA upper extremity muscle dysfunction are understudied. PURPOSE: To identify if novel non-invasive testing of RA forearm muscle oxidative capacity and biomechanical properties associate with traditional clinical and physiologic parameters. METHODS: RA participants (n = 12; mean age = 59.5 ± 8.0) underwent assessments in a cross-sectional design. Forearm flexor muscle oxidative capacity was assessed via near-infrared spectroscopy (NIRS) post-exercise oxygen consumption recovery (k). Passive muscle tone (oscillation frequency, Hz), stiffness (N/m) and elasticity (inverse of logarithmic decrement) of unilateral forearm flexor musculature were assessed using mechanical deformation with myotonometry via the MyotonPro® device. Additional assessments included RA disease activity (DAS-28), BodPod® body composition, hand grip dynamometry (kg), and cardiorespiratory fitness via cardiopulmonary exercise testing (VO2 peak; mL/kg/min). Correlations were compared using Spearman’s rho. RESULTS: RA forearm flexor muscle oxidative capacity (mean k = 1.11 ± 0.32) was strongly correlated with RA disease activity (mean DAS-28 = 3.76 ± 1.1; rho = 0.61, p = 0.034). Tone (mean = 16.8 ± 2.1 Hz) was strongly correlated with lean body mass (mean = 55.9 ± 10.9%;rho = 0.83, p = 0.001). Stiffness (mean = 316.4 ± 65.8 N/m) was strongly correlated with grip strength (mean = 24.1 ± 9.6 kg; rho = 0.59, p = 0.042). Elasticity (mean decrement = 1.25 ± 0.22) was strongly correlated with cardiorespiratory fitness (mean VO2 peak = 21.1 ± 4.5 mL/kg/min; rho = 0.61, p = 0.034). CONCLUSIONS: Unexpectedly, greater forearm muscle oxidative function associated with greater RA disease activity, possibly reflecting local muscle metabolic alterations to compensate for more severe hand and wrist arthritis. Conversely, greater RA forearm muscle tone, stiffness, and elasticity associated with better systemic muscle quality. These findings highlight the clinical and integrative physiology research potential for longitudinal monitoring of RA skeletal muscle metabolic and biomechanical health with non-invasive assessments.

P185 Patients' and clinicians' perspectives on the clinical utility of the Rheumatoid Arthritis Foot Disease Activity Index

Abstract Background/Aims Although patient-reported outcome measures (PROMs) are recommended in clinical practice, their application in primary care is limited. The Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5) is a validated PROM for assessing foot disease activity in rheumatoid arthritis (RA). This qualitative study aims to understand the clinical utility of the RADAI-F5 as a management tool for foot disease in RA. Methods Adult RA patients and rheumatologists, physiotherapists and podiatrists routinely involved in treating RA patients were recruited through convenience sampling. Recruitment continued until data saturation had been achieved. A 60-minute, semi-structured, one-on-one Microsoft Teams interview with participants was conducted. Interviews involved open-ended questions to explore barriers and facilitators to the clinical application of the RADAI-F5. These interviews were audio-recorded and transcribed verbatim, with each participant verifying the transcript to establish rigour and credibility. The transcripts were coded using Nvivo12, and inductive thematic data analysis was conducted to identify emerging themes. Results Eight RA participants: 7 females; mean [standard deviation, SD] age 52.4 [9.5], mean [SD] disease duration 16.1 [16.4] and eight clinicians; mean [SD] age 46.75 [5.3], mean [SD] years of clinical experience of 19.5 [2.21] participated. The RADAI-F5 has four key themes that support its clinical utility. These were as follows: ‘need for the RADAI-F5' because patients felt that feet were ignored during routine consultations and clinicians felt the need for a foot PROM that is accurate, short and quick to complete in clinical practice; ‘promoting patient-clinician communication' because it can identify areas of concern that may be under-recognized by clinicians; ‘guiding management' as implementing the RADAI-F5 could assist in the screening, monitoring foot disease status, and guiding future interventions; and ‘patient involvement,' since the tool may trigger patients to be more involved in their foot health self-management. Three themes were identified as potential barriers to implementation; ‘practical difficulties, including lack of time during appointments; ‘lack of validity', as clinicians were hesitant to use the RADAI-F5 until its validity is established further with the use of ultrasound imaging and clinical examination; and, ‘lack of an electronic database', since there is currently no electronic system for reporting RADAI-F5 results. Conclusion The results of this study suggest that the RADAI-F5 has significant potential as a clinical tool to aid foot disease management in RA. However, some barriers to implementation may need to be overcome to enable widespread uptake in rheumatology clinics. Disclosure A. Hoque: None.

Detection of salivary citrullinated cytokeratin 13 in healthy individuals and patients with rheumatoid arthritis by proteomics analysis.

The immune response to citrullinated peptides in the mucosa has been suggested to play an important role in the transition from pre-onset rheumatoid arthritis (RA) to clinically evident RA. Although there are reports indicating the presence of anti-citrullinated peptide antibodies in the saliva, few studies have reported citrullinated peptide detection in human saliva. This study aimed to identify citrullinated peptides in human saliva and discuss their clinical significance. Saliva samples were collected from 11 patients with RA and from 20 healthy individuals. Citrullinated peptides were detected using an anti-modified citrulline (AMC) antibody. Saliva from the healthy individuals was subjected to two-dimensional protein electrophoresis to isolate citrullinated peptides, which were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and mass spectrometry by peptide mass fingerprinting. The results were corroborated by immunoprecipitation (IP)-western blotting. The signal intensities of the bands precipitated with anti-cytokeratin 13 (CK13) and AMC antibodies were quantified. The signal intensity ratio of the band produced by the AMC antibody was divided by that of the band produced by the anti-CK13 antibody to calculate the citrullinated CK13 (Cit-CK13) ratio. A citrullinated peptide band corresponding to a molecular weight of approximately 50 kDa was detected in the saliva of healthy individuals, and identified as CK13 via mass spectrometry and IP-western blotting. No significant difference was observed between the salivary Cit-CK13 ratios of patients with RA and healthy participants (p = 0.605). This is the first study to show that Cit-CK13 is present in human saliva, and that there is no significant difference between the Cit-CK13 ratios of patients with RA and healthy individuals, suggesting that salivary Cit-CK13 content and RA development may not be associated. The physiological and pathological roles of Cit-CK13 in the oral cavity, and its responsiveness to mucosal immunity, remain unknown and will be the subject of further investigation.

Increased Risk of COVID-19 in Patients With Rheumatoid Arthritis: A General Population-Based Cohort Study.

ObjectivePatients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections owing to immunologic dysfunction and use of potent immunomodulatory medications; however, few data are available on their risk of COVID‐19. We estimated the rate of COVID‐19 among RA participants and compared it with that of the general population.MethodsUsing the Health Improvement Network, we identified RA patients before February 2020 and followed them to September 2020. We calculated the rate of COVID‐19 among participants with RA and compared it with that of the general population using a Cox proportional hazards model, adjusting for potential confounders using overlap weighting of exposure score. We repeated the same analysis among participants with osteoarthritis, a nonautoimmune rheumatic disease, as a negative control exposure.ResultsWe identified 225 cases of suspected and confirmed COVID‐19 among 17,268 RA patients, and 14,234 cases among 1,616,600 participants in the general population (1.4 versus 0.9/1,000 person‐months), with the adjusted hazard ratio (HRadj) being 1.19 (95% confidence interval [95% CI] 1.04–1.36). Confirmed COVID‐19 cases developed in 46 RA participants and in 2,249 in the general population (0.3 versus 0.1/1,000 person‐months), with the HRadj being 1.42 (95% CI 1.01–1.95). No statistically significant difference was observed for suspected and confirmed (HR 1.00 [95% CI 0.93–1.07]) or confirmed (HR 1.08 [95% CI 0.92–1.27]) COVID‐19 rates between participants with osteoarthritis and the general population.ConclusionRA, but not osteoarthritis, was associated with an increased risk of COVID‐19. Our findings provide timely evidence to support recommendations that booster vaccines and priority access to anti–SARS–CoV‐2 monoclonal antibody treatments should be encouraged for RA patients.

Interaction effect of systemic inflammation and modifiable rheumatoid cachexia risk factors on resting energy expenditure in patients with rheumatoid arthritis.

In rheumatoid cachexia (RC), high resting energy expenditure (REE) is associated with loss of muscle mass driven by proinflammatory cytokines. The objectives of this study were to investigate parameters associated with RC, and the interaction between systemic inflammation and modifiable risk factors for RC on REE. Thirty-five rheumatoid arthritis (RA) and nineteen non-RA controls comparable in age, sex, race and BMI underwent measures of REE by indirect calorimetry. Clinical, dietary, body composition and physical function data were collected. Homeostasis model assessment for insulin resistance (HOMA-IR) and serum interleukin-6 (IL-6) were used as parameters of IR and systemic inflammation, respectively. Regression models tested association between REE and dependent variables, including pre-specified interaction tests involving HOMA-IR and IL-6 and dietary intake of protein per weight (PPW) and IL-6. RA subjects were mostly women (94%) and had a median age of 54 years (50.5, 70) and BMI of 30.5 kg/m2 (26.1, 36.9). We observed a significant interaction effect between PPW and serum IL-6 on REE among RA subjects in the multiple regression model among RA. The upper tertile of PPW demonstrated a significant negative correlation between REE and IL-6 (β=-19.97, 95% CI [-35.41, -4.54], p=0.01). The lower tertile of PPW demonstrated a significant positive correlation between REE and IL-6 (β=42.24, 95% CI [4.25, 80.23], p=0.03). While IR can lead to muscle catabolism, IR was not significantly associated with REE in RA individuals. Higher dietary protein intake could attenuate the effect of systemic inflammation on REE in RA patients.