Rheumatoid Arthritis Disease Activity Research Articles

Attitudes towards technology supported rheumatoid arthritis care: investigating patient- and clinician-perceived opportunities and barriers.

Globally, demand outstrips capacity in rheumatology services, making Mobile Health (mHealth) attractive, with the potential to improve access, empower patient self-management and save costs. Existing mHealth interventions have poor uptake by end users. This study was designed to understand existing challenges, opportunities and barriers for computer technology in the RA care pathway. People with RA were recruited from Barts Health NHS Trust rheumatology clinics to complete paper questionnaires and clinicians were recruited from a variety of centres in the UK to complete an online questionnaire. Data collected included demographics, current technology use, challenges managing RA, RA medications and monitoring, clinic appointments, opportunities for technology and barriers to technology. A total of 109 patient and 41 clinician questionnaires were completed. A total of 83.5% of patients and 93.5% of clinicians use smartphones daily. However, only 25% had ever used an arthritis app and only 5% had persisted with one. Both groups identified managing pain, flares and RA medications as areas of existing need. Access to care, medication support and disease education were mutually agreeable opportunities; however, discrepancies existed between groups with clinicians prioritizing education over access, likely due to concerns of data overwhelm (80.6% considered this a barrier). In spite of high technology use and willingness from both sides, our cohort did not utilize technology to support care, suggesting inadequacies in the existing software. The lack of an objective biomarker for RA disease activity, existing challenges in the healthcare system and the need for integration with existing technical systems were identified as the greatest barriers. Registered on the Clinical Research Network registry (IRAS ID: 264690).

Correlation of Rheumatoid arthritis disease severity with serum vitamin D levels

Rheumatoid arthritis (RA) is an autoimmune disorder marked by characteristic inflammation of the small joints in addition to diverse systemic manifestations. Vitamin D has immunomodulatory properties, and its deficiency has a significant role in the clinical course of RA. The present research was conducted to study the correlation between serum vitamin D levels and disease activity scores in RA patients. A cross sectional study was carried out on a sample of 50 patients presenting with RA. Disease activity was measured using Modified Disease Activity Score (DAS) criteria. Estimation of serum Vitamin D levels were done using the electrochemiluminescence method and values less than 20ng/ml were considered as deficiency. Vitamin D levels were then correlated with disease activity scores. The Vitamin D deficiency was observed in 50% of the study population. Rheumatoid arthritis showed female preponderance in this study. Inflammatory markers such as C - reactive protein (CRP) levels and Erythrocyte Sedimentation Rate (ESR) did not differ with RA disease activity. More the number of large joints involved lesser were the vitamin D levels. There was an inverse correlation between Vitamin D levels and RA disease activity. Vitamin D deficiency is significantly correlated with disease severity of RA. This study points to the importance of screening for deficit of vitamin D among RA patients and treat it as early as possible.

How do symptoms of each joint contribute to global pain, disease activity and functional disability in rheumatoid arthritis?-A comprehensive association study using a large cohort.

Established assessment tools for patients with rheumatoid arthritis (RA), including disease activity scores (DASs), disease activity indexes (DAIs), visual analog scales (VASs), and health assessment questionnaires (HAQs), are widely used. However, comparative associations between joint involvement and disease status assessment tools have rarely been investigated. We included a dataset of 4016 patients from a large RA cohort from 2012 to 2019. The tenderness and swelling of each joint were counted as a symptom, with 70 and 68 affected joints throughout the body, respectively. The relative contribution of various joints to the disease status assessment tools, VAS scores, and functional disability indexes was analyzed using multiple regression analysis. The wrist showed the most significant contribution overall, especially in DASs and VASs, while the metacarpophalangeal and proximal interphalangeal joints made significant contributions to DASs and DAIs, but not to VASs and HAQs. The shoulder and the elbow significantly contributed to HAQs, but only the shoulder did to the VASs. The knee universally contributed to all of the tools, but the ankle played a minor but important role in most assessment tools, especially in HAQs. Similar but different contribution ratios were found between the sets of DASs, DAIs, VASs, or HAQs. Each joint makes a unique contribution to these assessment tools. The improvement or aggravation of symptoms in each joint affects the assessment tools in different manners.

Relationship between Clinical, Serological and Ultrasound Assessment of Rheumatoid Arthritis Activity

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissue that leads to damage of cartilage and bone, resulting in irreversible joint destruction. Aim of the Work Our study’s aim was to assess the relationship between systematic ultrasound (US) evaluation using 7-joint and 12-joint scores and both clinical and serological evaluations in the determination of disease activity in rheumatoid arthritis patients. Also, we assessed the difference between both scores to know which is more accurate in assessing disease activity. Patients and Methods It was a cross sectional study that was carried out on fifty-five Egyptian RA patients diagnosed according to the 2010 American College of Rheumatology (ACR)/EULAR criteria. Patients were recruited from the rheumatology outpatient clinic at Ain Shams university hospital. Results Regarding 7-joint score parameters, mean and standard deviation for GS synovitis was 5.72 ± 4.44, PD synovitis was 3.74 ± 5.24, GS tenosynovitis was 1.15 ± 1.68, PD tenosynovitis was 1.76 ± 3.44 and erosions 1.07 ± 1.37. Regarding the examined areas for 7-joint score, wrist dorsal synovitis was the most common synovitis (98%), 2nd metacarpo-phalangeal joint (56%) then 2nd metatarso-phalangeal joint (49%). Wrist dorsal tenosynovitis (36%) was the most frequent tenosynovitis. Radial (33%), dorsal erosions (18%) of 2nd metacarpo-phalangeal joint and radial erosions (13%) of 5th metatarso-phalangeal joint were the most common erosions found. Our study detected significant positive correlation (P value <0.05 and positive correlation coefficient) between majority of 7-joint and 12-joint score parameters (both GS and PD) and clinical disease activity variables, ESR, CRP and platelet count. Our study showed highly significant positive correlation (P value <0.01 and positive correlation coefficient) between all parameters of 7-joint and 12-joint scores. We found that 12 joint score is slightly better than 7 joint score in accuracy and sensitivity in assessing rheumatoid arthritis disease activity despite being more time-consuming. Conclusion The 7-joint and 12-joint ultrasound scores were simple and practical sum scoring systems for use in the detection of synovitis in patients with RA and in assessment of disease activity in synovium. The correlations between the clinical disease activity indices, ESR, CRP, platelet count and components of the 7-joint and 12-joint scores may indicate their value in assessment of disease activity and severity up to date. The composite score (Combined synovitis score) for 12-joint score was significantly differentiating between moderate-severe patient groups (classified according to DAS28) with P value 0.029, so 12-joint score was better in identifying minimal difference in disease activity despite being time-consuming.

Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis.

Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD. A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1. Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR. Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.

Soluble CD24 is an inflammatory biomarker in early and seronegative rheumatoid arthritis

Introduction Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by autoantibody production, joint inflammation and bone destruction. Nearly 1/3 of RA patients with the active disease also exhibit a normal range of ESR and CRP. Here we assessed the performance and clinical significance of soluble CD24 (sCD24) as a biomarker of disease activity in RA. Methods A total of 269 RA patients, 59 primary Sjogren’s syndrome (SS) patients, 81 systematic lupus erythematosus (SLE) patients, 76 osteoarthritis (OA) patients and 97 healthy individuals (HC) were included in this study. Soluble CD24 in sera were detected by ELISA. Therefore, the concentration of sCD24 was analyzed in RA patients with different disease activity statuses. Results The sCD24 was significantly increased in RA (2970 pg/mL), compared to other rheumatic diseases (380-520 pg/mL) and healthy individuals (320 pg/mL). Moreover, sCD24 was elevated in 66.67% of early RA and 61.11% of seronegative RA patients. In addition, sCD24 was significantly correlated with the disease activity duration and inflammatory indicators. There was an increased sCD24 in 64.23% of RA patients with normal ESR and CRP. Conclusion The sCD24 could be an inflammatory biomarker in RA patients, especially in early and seronegative patients.

Metabolic signature and proteasome activity controls synovial migration of CDC42hiCD14+ cells in rheumatoid arthritis.

Activation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes, the mechanism by which they perpetuate rheumatoid arthritis (RA), and how JAK inhibition mitigates these effects. CD14+ cells of 136 RA patients were characterized by RNA sequencing and cytokine measurement to identify biological processes and transcriptional regulators specific for CDC42 hiCD14+ cells, which were summarized in a metabolic signature (MetSig). The effect of hypoxia and IFN-γ signaling on the metabolic signature of CD14+ cells was assessed experimentally. To investigate its connection with joint inflammation, the signature was translated into the single-cell characteristics of CDC42 hi synovial tissue macrophages. The sensitivity of MetSig to the RA disease activity and the treatment effect were assessed experimentally and clinically. CDC42 hiCD14+ cells carried MetSig of genes functional in the oxidative phosphorylation and proteasome-dependent cell remodeling, which correlated with the cytokine-rich migratory phenotype and antigen-presenting capacity of these cells. Integration of CDC42 hiCD14+ and synovial macrophages marked with MetSig revealed the important role of the interferon-rich environment and immunoproteasome expression in the homeostasis of these pathogenic macrophages. The CDC42 hiCD14+ cells were targeted by JAK inhibitors and responded with the downregulation of immunoproteasome and MHC-II molecules, which disintegrated the immunological synapse, reduced cytokine production, and alleviated arthritis. This study shows that the CDC42-related MetSig identifies the antigen-presenting CD14+ cells that migrate to joints to coordinate autoimmunity. The accumulation of CDC42 hiCD14+ cells discloses patients perceptive to the JAKi treatment.

Platelet/lymphocyte, neutrophil/lymphocyte, and lymphocyte/monocyte ratios as biomarkers for rheumatoid arthritis: correlation with disease activity

BackgroundAssessment of disease activity in rheumatoid arthritis (RA) patients is essential for the adjustment of therapy. Inflammatory changes in lymphocytes, neutrophils, monocytes, and platelets supported the use of neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR) as markers of inflammation, we aimed to explore the clinical significance of PLR, NLR, and LMR in RA patients.ResultsThe study included 120 RA patients and 50 healthy matched controls. Clinical and laboratory data of the patients were assessed. Disease activity was measured using disease activity score (DAS28). Complete blood count (CBC) with differential count was used for the calculation of NLR, PLR, and LMR. Patients had significantly high NLR, and PLR (p < 0.001) and significantly low LMR (p < 0.001) when compared with the control group. Also, there were significant differences in the three ratios between patients in activity and those in remission (p < 0.001). Similarly, there were significant differences in all three ratios between patients with different degrees of disease activity. DAS28 score was positively correlated with NLR, PLR (r = 0.666, p < 0.001, r = 0.586, p < 0.001) and negatively correlated with LMR (r = 0.761, p < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that NLR had the highest sensitivity (86.9%) for RA disease activity, followed by PLR (85.9%) then LMR (76.2%), and regarding the specificity, NLR had high specificity (81%) followed by LMR (78%) then PLR (67%).ConclusionsGiven that NLR, PLR, and LMR were significantly different in patients when compared with the controls, also on comparing different degrees of disease activity and the three ratios were significantly correlated with DAS28 score, in addition to their good sensitivity and specificity for detection of RA disease activity, all this imply that they may be easy, reliable, cost-effective, and time-saving biomarkers when added to DAS28 score for the assessment of RA disease activity.

E06 Does GGT level correlate with activity parameters in enthesitis-related arthritis?

Abstract Introduction Enthesitis-related arthritis (ERA) is one of the main subgroups of juvenile idiopathic arthritis. As in the adult population, monitoring of patients with ERA is based on clinical and laboratory evaluation. Some studies showed a correlation between Gamma-glutamyl transferase (GGT) levels and rheumatoid arthritis disease activity markers. Thus, we aimed to evaluate the correlation between GGT levels and ERA activity parameters. Methods This is a cross-sectional monocentric study including patients meeting the International League of Associations for Rheumatology (ILAR) 2001 criteria for ERA. We collected the demographic and clinical data. We assessed the ERA activity using clinical parameters including Patient Global Assessment (PGA), Visual Analogue Scale (VAS), Morning stiffness (MS), tender joint count (TJC), swollen joint count (SJC), active enthesitis count (AEC), clinical sacroiliitis, back mobility, and ocular involvement. We collected biological parameters such as the C-reactive protein (CRP) and the Erythrocyte sedimentation rate (ESR). We calculated the Juvenile spondyloarthritis disease activity (JSpADA). GGT level was measured on the same day. The correlation was evaluated using Spearman’s rho coefficient (r). r-value &amp;lt;0.3 was considered poor; between 0.3 and 0.39, moderate; between 0.4 and 0.69, strong; and &amp;gt;0.7 very strong. Results Thirty patients with a mean age of 15.1 ± 4.1 years, and a ratio-sex of 2.75 were included. The mean disease duration was 4.3 ± 3.2 years. The mean PGA and the mean VAS were 6.2 ± 7.1 and 8.9 ± 2.9 respectively. Mean TJC, mean SJC, and mean AEC were 1.53 ± 2.8, 0.18 ± 0.47, and 1.2 ± 1.6 respectively. Clinical sacroiliitis was found in eight patients, limited back mobility in six, and uveitis in three patients. The mean CRP and ESR were 15.1 ± 22.7 mg/l and 23.8 ± 21.2 mm, respectively. The mean JSpADA was 2.6 ± 1.7. Mean GGT was 14.3 ± 6.6 mg/l. A strong correlation was noted between the GGT level and both CRP (r = 0.504, P = 0.05) and ESR (r = 0.601, P = 0.01). However, no correlation was noted between GGT level and PGA (r = 0.107, P = 0.6), VAS (r = 0.03, P = 0.9), SJC (r = -0.17, P = 0.368), nor JSpADA (r = 0.323, P = 0.87). Conclusion Our results suggest a strong correlation between GGT level and biological ERA activity parameters, unlike clinical parameters and disease activity scores. More studies are needed to confirm these findings. Ethics The authors have no conflicts of interest to declare.

Relationship Between Vitamin D and Neutrophil-Lymphocyte Ratio with Rheumatoid Arthritis Disease Activity

Introduction: Rheumatoid arthritis is a chronic inflammatory disease characterized by peripheral and symmetrical polyarthritis. Vitamin D deficiency has been linked to the course of several autoimmune diseases, and there is a link. In the process of autoimmune disease, the value of the neutrophil lymphocyte ratio is also known to be one of the parameters to assess the degree of activity. This study was conducted to assess the relationship between neutrophil lymphocyte ratio and rheumatoid arthritis disease activity. Method: This research is a cross-sectional study with a retrospective approach, conducted from January to March 2023. This research was conducted on rheumatoid arthritis sufferers at Haji Adam Malik Hospital, Medan. Subsequent research subjects underwent anamnesis and physical examination to assess the DAS28 score. Blood sampling for examination of the ratio of neutrophil lymphocytes and vitamin D was carried out at Haji Adam Malik Hospital. The data collected was then analyzed using SPSS version 26. Results: There were 67 research subjects with an age range of 43-47 years. The research subjects consisted of 20 men and 47 women. MTX treatment history in the remission group was 56.7%, in the low disease activity group was 80% and in the moderate disease activity group was 81%. Leflunomide treatment history in remission group 43.3%, low disease activity group 20% and moderate disease activity group 19%. Correlation test of vitamin D levels and rheumatoid arthritis disease activity showed a p-value of 0.380. Correlation test of neutrophil lymphocyte ratio and rheumatoid arthritis disease activity showed a p-value of 0.862. Correlation test of vitamin D levels and neutrophil lymphocyte ratio with DAS28 using the Spearman correlation showed­ p-values of 0.133. Conclusion: There was no significant relationship between vitamin D levels and neutrophil lymphocyte ratio with rheumatoid arthritis disease activity (p-value 0.133). Keywords: Vitamin D, Lymphocyte Neutrophil Ratio, DAS28, Rheumatoid Arthritis

Enhanced activity of the left precuneus as a predictor of visuospatial dysfunction correlates with disease activity in rheumatoid arthritis

ObjectiveTo identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI).MethodsA total of 27 RA patients (11 in remission, 16 in active) and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT. Brain activity data were collected using blood oxygen level dependent fMRI technique under MRT. Disease activity score 28 (DAS28) was used to evaluate the disease severity of RA patients. An analysis of the correlations between abnormal visuospatial-related brain regions, MRT performance, and DAS28 was conducted.ResultsRA patients performed worse on MRT than controls. Compared to the control group, RA patients showed enhanced activation in the left precuneus, left superior frontal gyrus and right cingulate gyrus during the rotation task, with left hemisphere dominance. RA patients in active showed enhanced activation in the left precuneus, left middle frontal gyrus and right cingulate gyrus compared to the patients in remission. The left precuneus activation was negatively correlated with MRT accuracy (r = −0.621, p = 0.01) and positively correlated with DAS28 (r = 0.710, p = 0.002), and MRT accuracy was negatively correlated with DAS28 in RA patients (r = −0.702, p = 0.002).ConclusionEnhanced activation of the left precuneus in RA patients affects visuospatial function and is closely related to disease activity. These changes may provide a valuable diagnostic neuroimaging biomarker of RA.

CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients.

Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.

Does Pizza Consumption Favor an Improved Disease Activity in Rheumatoid Arthritis?

To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of -0.70 for the DAS28-CRP, and -3.6 for the SDAI (overall analysis) and of -1.10 and -5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity.

Elevated Serum TIM-3 Correlates with Disease Activity of Rheumatoid Arthritis

Elevated Serum TIM-3 Correlates with Disease Activity of Rheumatoid Arthritis

Neutrophil-to-monocyte ratio is the better new inflammatory marker associated with rheumatoid arthritis activity.

Rheumatoid arthritis (RA) is a systemic autoimmune disease that chronically affects patients with episodes of inflammation. New inflammatory hematological markers were investigated for follow-up, such as the neutrophil-monocyte ratio (NMR), lymphocyte monocyte ratio (LMR), and neutrophil-lymphocyte ratio (NLR). This study was conducted to determine the most useful marker based on studies of association with RA disease activity and correlation with the classical markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF). This case-control study included 62 chronic RA patients who had previously been diagnosed and experienced episodes of symptoms while attending a variety of public and private rheumatology clinics in Ibb City, Republic of Yemen, for the period of September 1 to November 30, 2021. Twenty healthy volunteers were included in this study. Complete blood count, CRP, ESR, and RF levels were measured in all participants. The total leukocyte count, neutrophil count, platelet count, NMR, LMR, and NLR were positively correlated with CRP and ESR, but the monocyte count was reversed. The area under the curve (AUC = 0.861, 95% confidence interval [CI] = 0.769-0.948) for the NMR cutoff value of 4.7 was equal to that of CRP and close to that of ESR. This NMR cutoff value had 87% sensitivity and 80% specificity. LMR and NLR cutoff values of 4.35 and 1.35, respectively, resulted in AUCs of (AUC = 0.807, 95% CI, 0.708-0.905) and (AUC = 0.699, 95% CI, 0.571-0.819); their sensitivity and specificity were 62.3%, 90%, 57.4%, and 80%, respectively. As a convenient and low-cost inflammatory marker of RA activity, NMR outperformed LMR and NLR.

Relationships between physical activity levels and disease activity, functional disability and kinesiophobia in chronic rheumatic diseases

Relationships between physical activity levels and disease activity, functional disability and kinesiophobia in chronic rheumatic diseases

COVID-19 in Patients with Systemic Inflammatory Diseases: Impact on Disease Activity.

COVID-19 pandemic, an international emergency, raised concerns about the interaction of this infection and disease-modifying drugs used in the treatment of Systemic inflammatory diseases (SID). Understanding the relationship between COVID-19 and disease activity is crucial to adapt the treatment. The aim of our study was to determine the impact of COVID-19 on the disease activity of rheumatic diseases. We performed a cross-sectional study, including patients with SID (rheumatoid arthritis (RA) and spondyloarthritis (SpA)). Disease activity was evaluated during the last check-up before COVID-19 and within the period of 6 months after the infection. Activity scores were assessed with Disease Activity Score (DAS28) for RA and Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Correlation and regression coefficients were used to evaluate associations among the variables. Totally, thirty-two patients were included; twenty followed for RA and twelve for axial SpA. The mean disease duration of the underlying rheumatic disease was 10.2 years (2-30). RA was seropositive and erosive in 61% and 31%, respectively. Seventeen patients were on csDMARDs: 14 were on Methotrexate and three patients were on Salazopyrine. Ten patients (31%) were treated with bDMARDs; Tumor necrosis factor (TNF)-alpha inhibitors were used in eight cases. Rituximab and secukinumab were prescribed for one patient each. In 70%, COVID-19 was pauci-symptomatic. A severe form with a need for hospitalization was noted in 9%. Two patients were admitted to the intensive care unit (ICU). Overall, treatment with DMARDs was interrupted in all cases: when COVID-19 symptoms began in 82% and when PCR was positive in 18%. Both RA and axial SpA were not active after a mean period of 6 months after COVID-19 infection (p = 0.818 and p = 0.626, respectively). Although our patients interrupted their DMARDs, our study demonstrates that disease activity as assessed by ASDAS and DAS28 in SpA and RA remained unchanged after COVID-19.

Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis.

We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting. Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+ -related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti-tumor necrosis factor (anti-TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside. Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP-ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti-TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status. RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti-TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.

JAK-inhibitors and risk on serious viral infection, venous thromboembolism and cardiac events in patients with rheumatoid arthritis: A protocol for a prevalent new-user cohort study using the Danish nationwide DANBIO register.

Janus Kinase inhibitors (JAKis) are targeted synthetic disease-modifying antirheumatic drugs and represent an important alternative to treat patients with moderate to high rheumatoid arthritis (RA) disease activity. Safety concerns associated with increased risk for venous thromboembolism (VTE), serious viral infection, and, more recently, major adverse cardiovascular events (MACE) in JAKi users have emerged worldwide. However, as the exact mechanisms to explain these safety concerns remain unclear, the increased risk of VTE, MACE, and serious viral infection in JAKi users is heavily debated. In light of the need to enrich the safety profile of JAKis in real-world data, we aim to quantify the incidence and risk of MACE, VTE, and serious viral infections in RA patients registered in the Danish DANBIO registry, a nationwide registry of biological therapies used in rheumatology. Therefore, we will conduct a population-based cohort study using a prevalent new-user design. We will identify all RA patients in the DANBIO, ≥ 18 years old, receiving a JAKi or a tumor necrosis factor α inhibitor (TNF-αi) from January 2017 to December 2022. Prevalent and new users of JAKis will be matched to TNF-αi comparators with similar exposure history using time-conditional propensity scores (TCPS). We will describe the cumulative incidence of the outcomes (VTE, MACE, serious viral infection) in each exposure group (JAKi users; TNF-αi users), stratified by outcome type. Additionally, the Aalen-Johansen method will be used to estimate the time-to-event survival function stratified by outcome type. We will also estimate the hazard ratio (HR) with 95% confidence interval (CI) of each outcome in both exposure groups using the time-dependent Cox proportional hazards model. Results will enrich the safety profile of JAKis in real-world data.

Heat of the night: sleep disturbance activates inflammatory mechanisms and induces pain in rheumatoid arthritis.

Sleep has a homeostatic role in the regulation of the immune system and serves to constrain activation of inflammatory signalling and expression of cellular inflammation. In patients with rheumatoid arthritis (RA), a misaligned inflammatory profile induces a dysregulation of sleep-wake activity, which leads to excessive inflammation and the induction of increased sensitivity to pain. Given that multiple biological mechanisms contribute to sleep disturbances (such as insomnia), and that the central nervous system communicates with the innate immune system via neuroendocrine and neural effector pathways, potential exists to develop prevention opportunities to mitigate the risk of insomnia in RA. Furthermore, understanding these risk mechanisms might inform additional insomnia treatment strategies directed towards steering and reducing the magnitude of the inflammatory response, which together could influence outcomes of pain and disease activity in RA.