Rheumatoid Arthritis Disease Duration Research Articles

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial

BackgroundTreatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.MethodsIn this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR.ResultsWe studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms.ConclusionsBoth treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT.Trial registrationClinicalTrials.gov ID NCT02374021.

Erosive Progression by High-Resolution Peripheral Quantitative Computed Tomography and Conventional Radiography in Rheumatoid Arthritis.

To investigate the diagnostic accuracy of high-resolution peripheral quantitative computed tomography (HR-pQCT) to assess erosive progression during one year compared to conventional radiography (CR) in rheumatoid arthritis (RA). This prospective study included 359 patients with RA (disease duration ≥ 5 years) between March 2018 and October 2020. HR-pQCT and CR were obtained at inclusion and after one year. Erosive assessment was performed at two metacarpophalangeal joints of the dominant hand using HR-pQCT and progression was defined as an increase in erosion number ≥ 1 or an increase in erosive volume > least significant change. CR of hands, wrists, and feet were evaluated using Sharp/van der Heijde scores and erosive progression was defined as a 1.1-point increase in erosion score according to the smallest detectable change. In paired analyses (n = 310), erosive progression was identified in 30 patients using CR and in 40 patients using HR-pQCT. In the 40 patients with erosive progression on HR-pQCT, progression was not identified by CR in 33 patients. Adding HR-pQCT to CR doubled the proportion of patients identified with progression from 30 (10%) to 63 (20%) patients. Using CR as the reference, the sensitivity (% (95% CI)) of HR-pQCT for identifying erosive progression was 23.3 (9.9-42.3) and the specificity was 88.2 (83.8-91.7). A substantial proportion of patients with erosive progression are overlooked using CR only to monitor erosive progression. Adding high-resolution peripheral CT to CR doubles the proportion of patients, who may benefit from individualised therapy targeting erosive progression in RA.

A study of carotid intima media thickness in patients with rheumatoid arthritis and its correlation with acute phase reactants and disease activity

Introduction: There is increased risk of cardiovascular morbidity and mortality in patients of rheumatoid arthritis (RA) due to accelerated atherosclerosis. In this study we measured Carotid artery intima media thickness (CIMT) as a surrogate marker for subclinical atherosclerosis in RA patients without pre-existing cardiovascular disease. This study also analyzed the correlation between CIMT, disease duration, Simplified Disease Activity Index (SDAI) and acute phase reactants. Methods: A cross-sectional study was conducted on 90 patients divided into two groups of 45 patients of RA and another 45 control subjects. Subjects with RA and age and sex matched healthy controls were included in the study without pre-existing CV risk factors. Complete clinical evaluation, hematological and biochemical profile done. ESR, CRP and platelet count were used as markers of acute phase reactants. All the RA patients included in the study were evaluated for their disease activity using Simplified Disease Activity Index (SDAI). All the subjects including the controls evaluated for carotid intima media thickness by using carotid ultrasonography. CIMT measured in common carotid artery bilaterally by examining throughout common carotid artery up to 2 cm proximal to bifurcation. CIMT measurement taken at the site of greatest thickness. All measurements taken in diastole, measured in phase when lumen diameter is at its smallest and IMT at its largest. Mean value of 6 readings (3 from each side) taken as final CIMT for evaluation. B mode (linear probe) USG was used to determine carotid IMT. Results: 45 cases and similar control subjects included in the study with mean age (SD) as 45.07 (14.81) years. We found female preponderance with 37 females out of 45 cases. Mean (SD) disease duration in male subjects was 5.38(2.40) years while in females was 5.09 (2.78) years. CRP was found to be significantly increased in cases group with mean (SD) of 5.75(8.85) mg/dl. ESR significantly raised to 35.22(13.55) mm/hour in cases group compared to control group where it was 16.16(5.71) mm/hr. Mean (SD) platelets (x10³/mm³) were 229.24(69.80) in cases while controls had 290.33(83.85), so platelets correlation with disease could not be established. CIMT was significantly raised in cases group. Mean (SD) CIMT in cases was 0.95(1.06) mm whereas in control group it was 0.60(0.16) mm with p value of 0.002. Moderate positive correlation was found between CIMT (mm) and SDAI and this correlation was statistically significant with p=0.001. For every 1 unit increase in CIMT, the SDAI increases by 2.92 units. A strong positive correlation between CIMT (mm) and Disease Duration (Years), and this correlation was statistically significant (rho = 0.9, p = <0.001). For every 1 unit increase in CIMT (mm), the Disease Duration (Years) increases by 1.26 units. Conversely, for every 1 unit increase in Disease Duration (Years), the CIMT (mm) increases by 0.19 units. Conclusion: A strong correlation was observed between CIMT and disease duration in rheumatoid arthritis. Hence, CIMT can be a useful surrogate marker for detecting atherosclerosis in patients with RA. In view of the relation to duration of disease, established RA patients should regularly be screened to identify the evidence of atherosclerosis and manage it earlier. Prevention of cardiovascular disease in RA requires an integrated approach encompassing cardiovascular risk factors screening and management, effective and sustained control of RA disease activity, high index of suspicion and prompt investigation of suspected cardiac disease.

P052 Rheumatoid arthritis associated risk of venous thromboembolism is not dependent on disease duration: United Kingdom-based population study

Abstract Background/Aims Risk of venous thromboembolism (VTE) is higher in patients with rheumatoid arthritis (RA) compared to the general population; however, whether this risk changes with RA disease duration remains poorly understood. Acknowledging potential heterogeneity in risk by RA duration could support more tailored screening and effective preventive approaches. In a large population-based study, we aimed to characterise the RA-attributable VTE risk in patients with varying disease durations. Methods Adults registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) primary care database. RA patients (diagnosed prior to and during the study period), VTE outcome (as a composite of pulmonary embolism [PE] or deep vein thrombosis [DVT]) and individual PE and DVT outcomes were determined using previously validated algorithms. RA-unaffected controls (UCs) were matched 4:1 with RA patients by current age, sex, calendar time, and years since practice registration using nearest neighbour matching with replacement. Absolute VTE, PE and DVT rates over 20 years were compared in RA patients versus matched UC across four subgroups defined by disease duration (0-2, 2-5, 5-10 and ≥10 years since diagnosis). Across the same subgroups, relative risks over the same period were estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (body-mass index [BMI], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results 117,050 individuals were included, of whom 93,640 were UCs and 23,410 were RA patients. Among those with RA, 63.9% were included at or within two years of diagnosis, 7.8% within two to five years of diagnosis, 9.8% within five to ten years of diagnosis, and 18.5% more than 10 years after diagnosis. Average study follow-up for the primary outcome (VTE) was 8.2 years (standard deviation [SD]=6.6 years). RA patients (mean age 59.0, SD 15.5; 28.9% male [n = 6776]; mean BMI 27.1, SD 5.6) were similar to matched UCs in clinical characteristics. Unadjusted VTE events rates were consistently higher in RA patients compared to UCs across all subgroups. Relative risk of VTE was similarly increased in RA patients compared to the general population regardless of the time elapsed since RA diagnosis (adjusted hazard ratios [aHR] range: 1.49-1.63, all p < 0.001). The results obtained when PE (aHR range 1.46-2.02, all p < 0.001) and DVT (aHR range 1.43-1.89, all p < 0.001) were analysed separately were similar to those observed in the composite outcome. Conclusion Healthcare professionals should recognize that individuals with RA face a consistently elevated VTE risk compared to the general population, irrespective of disease duration. This highlights the need for vigilant monitoring and assessment of VTE risk factors even in early-stage cases. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. S. Rana: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; M.H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

Polyautoimmunity in Patients With Anticyclic Citrullinated Peptide Antibody-Positive and -Negative Rheumatoid Arthritis: a Nationwide Cohort Study From Denmark.

This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative patients with rheumatoid arthritis (RA). In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP-positive vs anti-CCP-negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. The study included 5839 anti-CCP-positive and 3799 anti-CCP-negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP-positive and anti-CCP-negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP-negative patients developed autoimmune disease.

Associations Between Rheumatoid Arthritis Clinical Factors and Synovial Cell Types and States.

Recent studies have uncovered diverse cell types and states in the rheumatoid arthritis (RA) synovium; however, limited data exist correlating these findings with patient-level clinical information. Using the largest cohort to date with clinical and multicell data, we determined associations between RA clinical factors with cell types and states in the RA synovium. The Accelerated Medicines Partnership Rheumatoid Arthritis study recruited patients with active RA who were not receiving disease-modifying antirheumatic drugs (DMARDs) or who had an inadequate response to methotrexate (MTX) or tumor necrosis factor inhibitors. RA clinical factors were systematically collected. Biopsies were performed on an inflamed joint, and tissue were disaggregated and processed with a cellular indexing of transcriptomes and epitopes sequencing pipeline from which the following cell type percentages and cell type abundance phenotypes (CTAPs) were derived: endothelial, fibroblast, and myeloid (EFM); fibroblasts; myeloid; T and B cells; T cells and fibroblasts (TF); and T and myeloid cells. Correlations were measured between RA clinical factors, cell type percentage, and CTAPs. We studied 72 patients (mean age 57 years, 75% women, 83% seropositive, mean RA duration 6.6 years, mean Disease Activity Score-28 C-reactive Protein 3 [DAS28-CRP3] score 4.8). Higher DAS28-CRP3 correlated with a higher T cell percentage (P < 0.01). Those receiving MTX and not a biologic DMARD (bDMARD) had a higher percentage of B cells versus those receiving no DMARDs (P < 0.01). Most of those receiving bDMARDs were categorized as EFM (57%), whereas none were TF. No significant difference was observed across CTAPs for age, sex, RA disease duration, or DAS28-CRP3. In this comprehensive screen of clinical factors, we observed differential associations between DMARDs and cell phenotypes, suggesting that RA therapies, more than other clinical factors, may impact cell type/state in the synovium and ultimately influence response to subsequent therapies.

Cross-sectional association between social and demographic factors and disease activity in rheumatoid arthritis

BackgroundThis study aimed to assess the association between social factors, demographic parameters, and disease activity among rheumatoid arthritis (RA) patients.MethodsThe University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry was used for this study and included patients meeting 1987 ACR criteria for RA enrolled between 2010–2015. The registry collected clinical and laboratory data at each visit, permitting the calculation of disease activity measures that included Disease Activity 28-C Reactive Protein (DAS28-CRP). The current study was conducted as a cross-sectional study in which baseline data were used to construct multiple logistic regression models assessing the relationship between disease activity measures (DAS28-CRP), functional capacity (health assessment questionnaire (HAQ)), selected demographic and social factors (occupation, education, income, marital status, race, gender, age, and BMI), and clinical/laboratory variables.ResultsThe analyses included 729 patients with baseline DAS28-CRP and social/demographic data. The mean age at enrollment was 59.5 (Standard Deviation (SD) = 12.7) years, 78% were female, and the median RA disease duration was 9.8 (Interquartile Range (IQR): 3.7, 19.1) years. We dichotomized the DAS28-CRP score and defined scores above or below 3.1 as high versus low RA disease activity. Most patients with high RA disease activity (N = 326, 45%) had less than a college degree (70%), were not working/retired/disabled (71%), and had an annual income under $50 K (55%). We found that higher body mass index (BMI) (Odds Ratio (OR) = 1.04, 95% CI: 1.01—1.08), longer disease duration (> 2 and < 10 years versus ≤ 2 years of disease) (OR = 0.45, 95% CI: 0.25—0.78), and being retired (OR = 1.74, 95% CI: 1.02—2.98) were associated with RA disease activity.ConclusionIncreased RA activity may be associated with various social factors, potentially leading to more severe and debilitating disease outcomes. These findings provide evidence to support efforts to monitor disparities and achieve health equity in RA.

Periodontal health status, Porphyromonas gingivalis and anti-cyclic citrullinated peptide antibodies among rheumatoid arthritis patients

Porphyromonas gingivalis (P. gingivalis) is the primary periodontal pathogen involved in protein citrullination, which triggers the production of anti-cyclic citrullinated peptide (anti-CCP) antibodies, exacerbating rheumatoid arthritis (RA). This study aims to evaluate the amount of P. gingivalis and its association with anti-CCP antibodies in RA patients with periodontitis. This cross-sectional study involves 100 RA patients with a mean age of 52.36 (SD 13.90) years. Smokers and patients with other uncontrolled systemic diseases were excluded. Disease Activity Score-28 (DAS-28) was used to determine RA disease severity. Periodontal parameters were examined to determine periodontal status. Subsequently, plaque samples were collected from the subgingival periodontal pocket for assessment of P. gingivalis bacterial load using the loop-mediated isothermal amplification method. Blood samples (5 ml) were obtained from all participants to analyse anti-CCP antibody levels. Data was analysed by using SPSS version 24.0. Most participants were female (85.0%) and had low RA disease severity (62%). The mean RA disease duration was 7.77 (SD 6.3) years, with a mean DAS-28 of 3.17 (SD 1.0). Forty-seven per cent of participants had periodontitis, but all periodontal parameters were not associated with RA disease activity (P = 0.38). P. gingivalis bacterial load ranged from 10 to 109 copies/μl. Fifty-five per cent of the collected samples showed positive anti-CCP antibody levels, but no significant association was observed with the P. gingivalis bacterial load (P = 0.58). Considering the study's limitations, although periodontitis is prevalent among RA patients, there is a lack of association between P. gingivalis bacterial load and anti-CCP antibody levels, which should be investigated further.

Carpal Tunnel Syndrome in Rheumatoid Arthritis Patients

Abstract Background Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). Aim and objectives to assess the presence and severity of Carpal tunnel syndrome in rheumatoid arthritis patients and its relation to disease activity. Patients and Methods This is observational cross sectional study, was carried out 30 rheumatoid arthritis patients recruited from Ain Shams University Hospital)inpatient internal medicine department and rheumotology outpatient clinic) in the period from November (2018) till November (2020). Result Only ultrasound assesment of CTS by measuring Of CSA&amp;gt;10 at wrist showed significant positive correlation with RA Patients ages, RA disease duration, CTS symptoms duration, CRP, RF and anti ccp positivity and negative correlation with HB% indicating association with disease compare to others activity. Conclusion CTS frequency in RA is found higher than normal population, especially in patients with additional risk factors of CTS. There was no relationship between CTS and disease activity, and CTS group had long disease duration and worse functional status. CTS could be a result of the chronic course in RA.

Sex Differences in Pain and Quantitative Sensory Testing in Patients With Rheumatoid Arthritis.

Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference, and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count, and C-reactive protein. Mean ± SD pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83 [95% confidence interval (95% CI) 0.14, 1.53]). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22 [95% CI -1.73, -0.72]), wrist (adjusted difference -0.57 [95% CI -1.07, -0.06]), and knee (adjusted difference -1.10 [95% CI -2.00, -0.21]). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

High‐resolution peripheral quantitative computed tomography for the evaluation of bone erosions of metatarsophalangeal joints in patients with rheumatoid arthritis

AbstractObjectivesTo compare if the 4th and 5th metatarsophalangeal (MTP) joints evaluated by high‐resolution peripheral quantitative computed tomography (HR‐pQCT) could classify more patients with erosive rheumatoid arthritis (RA) compared with conventional radiography (CR) of the hands, wrists, and feet. Furthermore, we characterize and quantify bone erosions in the two MTP joints by HR‐pQCT.MethodsThis single‐center cross‐sectional study included patients with established RA (disease duration ≥5 years). Blinded to patient data, the number and volume of erosions in the 4th and 5th MTP joints were measured by HR‐pQCT, whereas the erosive scores by CR of 44 joints in the hands, wrists, and feet were assessed according to the Sharp/van der Heijde method.ResultsAmong 42 participants, 30 patients were classified with erosive RA and 12 with non‐erosive RA by CR. HR‐pQCT of two MTP joints could classify more patients with erosive RA compared with CR of 44 joints (p = .03). The optimal cut‐off value for the number and volume of erosions per patient in the 4th and 5th MTP joints by HR‐pQCT was 7.5 erosions and 11.7 mm3, respectively, for detecting erosive disease by CR. Erosions in the two MTP joints by HR‐pQCT were found most frequently and were largest at the lateral quadrant of the 5th metatarsal head.ConclusionThe superiority of HR‐pQCT of the 4th and 5th MTP joints compared with CR of 44 joints for classifying erosive RA provides a basis for larger studies evaluating if HR‐pQCT could be used for diagnosing erosive RA in the future.

Male rheumatoid arthritis patients at substantially higher risk for cardiovascular mortality in comparison to women

BackgroundPatients with rheumatoid arthritis (RA) are at an increased risk for developing cardiovascular diseases. While advice regarding cardiovascular risk screening and management in RA patients has been incorporated in several guidelines in recent years, its implementation and adherence is still poor. ObjectivesTo assess the cardiovascular disease risk in new diagnosed RA patients and evaluate whether advice to initiate preventive medical treatment of high risk patients was followed. MethodsAll patients with a recent diagnosis of RA, aged 40–70 years, were screened between May 2019 and December 2022 for cardiovascular diseases and risk factors within the first year after diagnosis at the outpatient rheumatology clinic, as part of standard care. Screening included a physical examination with blood pressure measurement, and laboratory tests with lipid profile tests. All patients and their general practitioner (GP) received an overview with their cardiovascular risk profile and a calculated 10-year cardiovascular mortality risk. Cardiovascular risk was defined as low (<1%), intermediate (1–5%), high (5–10%) and very high (>10%). The national pharmacy network was consulted to check whether or not patients started preventive medication after screening. ResultsA total of 125 RA patients was included in this study. The mean age was 56 years and 78% was female. Median RA disease duration at screening was 6 months. Six patients (5%) indicated to have been screened before, and used antihypertensive medication. During screening, hypertension was found in 57% of male patients and 43% of female patients and dyslipidemia was found in 36% in male and 32% in female patients. 46% of male patients and 21% of female patients currently smoked. A high or very high 10-year cardiovascular mortality risk was found in 50% of male patients, but in only 4% of female patients. Only 26% of (very) high risk patients started antihypertensive or statin medication after screening. ConclusionsAn increased cardiovascular disease risk is often present in newly diagnosed RA patients, especially male patients, with a large proportion having undiagnosed and untreated hypertension and hypercholesterolemia. Even with structural screening and informing of the patients and GPs, treatment of cardiovascular risk factors in high risk patients remains insufficient. CV risk screening needs to be part of standard care for RA patients, with clear agreement on the responsibilities between primary and secondary care. Awareness of the importance of CVD risk screening needs to improve among both RA patients themselves and the GPs to ultimately reduce the cardiovascular burden of our patients. Obviously, a better collaboration between GPs and rheumatologists is urgently needed to lower the cardiovascular burden of our patients.

P145 Association between musculoskeletal ultrasound and the Rheumatoid Arthritis Foot Disease Activity Index in managing the rheumatoid foot

Abstract Background/Aims In rheumatoid arthritis (RA), foot synovitis is frequently evident in patients in DAS-28 remission, placing them at risk of radiographic joint damage. This has been attributed to the omission of foot and ankle joint counts from the DAS-28. The Rheumatoid Arthritis Foot Disease Activity Index (RADAI-F5) is a valid, reliable, and feasible tool and can be used as an adjunct to the DAS-28 to quantify foot disease activity. Recent qualitative research suggests that rheumatologists perceive validation of the RADAI-F5 against musculoskeletal ultrasonography (MSUS) as essential prior to clinical implementation. Accordingly, this study aimed to evaluate the construct validity of the RADAI-F5 relative to MSUS and clinical examinations of foot disease activity. Methods People with RA were recruited from 3 NHS Rheumatology Outpatient services in Scotland. Participants attended a single research visit and completed the RADAI-F5. An MSUS-trained podiatrist performed multi-planar grayscale (GS) and power Doppler (PD) MSUS assessments on 17 regions of each foot, including joints and soft tissues and evaluated foot disease activity using summated scores based on semi-quantitative grading systems for synovial hypertrophy, PD synovitis, tenosynovitis (0-39) and presence/absence of erosions (0-7). An independent examiner clinically assessed the same 17 regions for swelling and tenderness and scored using a summated score for presence/absence (0-17). The construct validity of the RADAI-F5 was assessed using Spearman’s correlation coefficients with 95% confident intervals (95% CI) to test a priori-specified hypotheses for strength of associations. Results Of 60 participants, 48 were female, with a mean [standard deviation, ± SD] age of 62.6 ± 9.96 and median RA disease duration of 10 (interquartile range 6-20.5) years. For DAS28-ESR disease categories, 10% were in remission, 35% had low disease activity, 18.3% had moderate disease activity, and 36.7% had high disease activity. Forty-three participants were receiving DMARD therapy, and 17 were receiving biologics. Theoretically consistent associations confirming construct validity [95% CI] were observed between the RADAI-F5 and MSUS GS-detected synovial hypertrophy (0.72 [0.57-0.82]; strong) and MSUS PD-detected synovitis (0.50 [0.28-0.67]; moderate), MSUS-detected erosions (0.42 [0.19-0.61]; moderate) and clinical tenderness (0.52 [0.31-0.68]; moderate), and swelling (0.35 [0.11-0.55]; weak). Conclusion Moderate-strong associations between RADAI-F5 and MSUS provide additional evidence of the excellent measurement properties of this tool. The RADAI-F5 scores, as anticipated, were more strongly associated with MSUS-detected synovial hypertrophy compared to clinical examinations of swelling and tenderness. With increased confidence in the RADAI-F5's validity, clinical implementation of the RADAI-F5 could help with the early identification of people with RA who are at risk of poor functional and radiographic outcomes. The RADAI-F5 has the potential for use in a broad range of clinical applications within podiatry and rheumatology, including triage, enhanced multidisciplinary team and patient-clinician communication, and remote consultations. Disclosure A. Hoque: None. M. Steultjens: None. D. Dickson: None. G.J. Hendry: None.

Characteristics of atherosclerotic plaque and the thickness of the carotid artery intima-media complex in patients with rheumatoid arthritis

Background/Aim. Rheumatoid arthritis (RA) represents an independent risk factor for the development of cardiovascular (CV) disease (CVD). Early detection of atherosclerotic changes is of tremendous importance in the prevention of CV events. An increase in the carotid artery intima-media thickness (cIMT) is considered a sensitive marker of early subclinical atherosclerosis. The aim of our investigation was to assess the cIMT, the number and type of carotid plaques (CPs), and the severity of carotid artery stenosis in RA patients. Furthermore, we investigated the correlation between all the above-mentioned parameters and disease duration and activity. Methods. The research included 92 participants, of which 58 were patients with RA, and the remaining 34 participants were healthy individuals (control group). In patients with RA, clinical examination and laboratory findings were used for assessing disease activity. All participants underwent a color Doppler ultrasound examination of the carotid arteries with a linear probe in order to assess cIMT, the number and type of CPs, as well as the se-verity of stenotic lesions. Results. The mean cIMT in RA patients was statistically significantly higher compared to the control group (0.8 ? 0 .2 mm vs. 0.7 ? 0.2 m m; p &lt; 0.01). CPs were found in 34 out of 58 RA patients (58.6%) and 4 out of 34 (11.8%) participants in the control group (p &lt; 0.001). The number of CPs per patient was significantly higher in the RA group compared to the control group (1.4 ? 0.9 vs. 0.2 ? 0.4; p &lt; 0.001). The cIMT, the presence and number of CPs, and the severity of carotid artery stenosis were not statistically significantly related to disease activity. There was a statistically significant direct correlation between the duration of RA and the percent-age of carotid arterial stenosis (r = 0.320, p = 0.034). Conclusion. The cIMT and the presence and number of CPs per patient were significantly higher in RA patients. More-over, there was a positive correlation between RA disease duration and the severity of carotid artery stenosis. This study showed that RA represents an independent risk factor for an increase in cIMT and the development of sub-clinical atherosclerosis.

Impact of disease duration on proteomic bioprofile and prognosis in rheumatoid arthritis patients.

Cardiovascular disease worsens the prognosis of rheumatoid arthritis (RA) and vice-versa. Inflammation may be a common pathway for both conditions. It is expected that a longer RA duration leads to a greater inflammatory cumulative exposure burden; however, studies on the association between RA disease duration and outcomes are scarce. Our aim is to compare the characteristics, biomarker expression and outcomes according to the duration of RA. Prospective cohort study including 399 RA patients, with detailed clinical, echocardiographic, and proteomic phenotyping that were compared across tertiles of RA disease duration. Cox proportional models were used to study the association of disease duration with cardiovascular outcomes. RA duration tertiles were: tertile 1 with median of 3.2; tertile 2 with median of 8.8; and tertile 3 with median of 21.8 years. Compared to tertile 1, patients in tertile 3 were older, had more erosive disease, more frequent echocardiographic alterations, lower haemoglobin and walked a shorter distance on the 6MWT. Natriuretic peptides, cathepsin L1, galectin 9, matrix metalloproteinase-12, adrenomedullin and tumour necrosis factor receptor 11A were higher in patients with longer disease duration. Compared to patients in tertile 1, those in tertile 3 had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death (HR 2.71, 95%CI 1.06-6.92, p=0.04). RA patients with longer disease duration had more organ damage and worse outcomes than those with shorter disease duration. Biomarker expression suggested that patients with longer RA duration had activation of pathways related to inflammation, extracellular matrix organisation, fibrosis and congestion.

Muscle mass loss is associated with physical dysfunction in patients with early rheumatoid arthritis.

Muscle mass loss is common in long-standing rheumatoid arthritis (RA). The aim was to explore the prevalence and effects of RA disease characteristics in patients with early RA. This cross-sectional study was carried out based on a Chinese RA cohort and control subjects. The body composition (BC) was assessed using bioelectric impedance analysis. Myopenia was defined by an appendicular skeletal muscle mass index of ≤ 7.0 kg/m2 in men and ≤ 5.7 kg/m2 in women. Physical dysfunction was defined as a health assessment questionnaire disability index > 1. Propensity score matching was performed to balance age and gender differences among patients with early RA (disease duration ≤ 12 months) and established RA, and controls (with 1:3:3 matching). In total, 2017 controls and 1,008 patients with RA were recruited for this study. Among the patients with RA, there were 190 (18.8%) patients with early RA, with a median disease duration of 7 (4, 11) months. The matched patients with early RA (n = 160) showed a higher prevalence of myopenia than the matched controls (41.3 vs. 15.8%, P < 0.0167), but no difference was found in the matched patients with established RA (41.3 vs. 50.4%, P > 0.0167). Compared with the patients with established RA, the patients with early RA exhibited higher disease activity scores [disease activity score in 28 joints with four variables including C-reactive protein (DAS28-CRP): median 4.76 vs. 3.93, P < 0.001] and a higher prevalence of physical dysfunction (26.3 vs. 19.4%, P = 0.035). In the patients with early RA, patients with myopenia showed a higher prevalence of physical dysfunction than those without myopenia (41.3 vs. 15.5%, P < 0.001), among which walking and common daily activities were the most involved subdimensions. Multivariate logistic regression analysis showed that DAS28-CRP was positively associated with myopenia [adjusted odds ratio (AOR) 1.558, 95% CI (1.138-2.132)], and myopenia [AOR 2.983, 95% CI (1.192-7.465)] was independently associated with physical dysfunction in the patients with early RA. Our data indicate the importance of early detection of muscle involvement in the early stage of RA and imply the significance of early aggressive control of disease activity for the prevention of myopenia and physical dysfunction in patients with early RA. Our study provides a new perspective on RA management.

Chinese registry of rheumatoid arthritis (CREDIT) V: sex impacts rheumatoid arthritis in Chinese patients.

The impact of sex on the clinical manifestations of rheumatoid arthritis (RA) were diversely reported in the literature. The Chinese Registry of rhEumatoiD arthrITis provides a platform for the investigation of this issue in Chinese patients. Demographic and clinical parameters were collected from all enrolled patients with RA and from patients with early RA (disease duration ≤6 months). The differences in data regarding disease activity, comorbidities, and medications for RA were compared between men and women. The proportions of patients who achieved remission and low disease activity were compared at enrollment and during 3-, 6-, and 12-month follow-up visits. A total of 11,564 patients were enrolled, 83.6% of whom were female. In all the enrolled patients and patients with early RA, C-reactive protein (CRP, 12.0 vs . 6.7 mg/L), pain visual analogue scale (4.8 vs . 4.5), patient's and physician's global assessment (4.9 vs . 4.5 and 4.9 vs . 4.5), 28-joint disease activity score using DAS28-CRP (4.3 vs . 4.0) simplified disease activity index (21.9 vs . 19.9), and clinical disease activity index (19.3 vs . 18.0) were significantly higher in men than in women. Additionally, the swollen joint count/tender joint count and DAS28 using erythrocyte sedimentation rate were higher in male patients than in female patients with early RA. More female patients with early RA reached the treatment target at baseline than male patients (23.4% vs . 18.2%, assessed by CDAI). At 3 months, 6 months, and 12 months, the proportion of remission and treatment target achievement was similar in both sexes. Coronary artery disease (CAD) and stroke were more frequent in men than in women. In Chinese patients with RA, men were found to have more active disease, as well as more cases of CAD and stroke. Therefore, sex should be carefully considered during the personalization of RA treatment.

AB1346 ULTRASOUND ASSESSMENT OF SUB-CLINICAL HAND JOINT INFLAMMATION: A COMPARATIVE STUDY BETWEEN EARLY RHEUMATOID AND PSORIATIC ARTHRITIS

BackgroundUltrasound (US) detected subclinical inflammation can be present in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA), and also in patients fulfilling clinical remission criteria[1-2]. Numerous evidences support that the persistence of subclinical synovitis detected by US is associated with a high risk of disease progression [2-3].ObjectivesTo evaluate sub-clinical inflammation of PsA and RA at the level of small joints of the hand and wrist by B-mode and Power Doppler US.Methods30 patients of early PsA and 35 patients of early RA (no clinical evidence of hand joint involvement, PsA disease duration &lt;2 years, and RA disease duration &lt;1 year) were recruited. US [grey scale (GS) and power Doppler (PD)] was performed to assess synovitis, tenosynovitis, joint effusion, and bone erosion of bilateral wrists, metacarpophalangeal joints, proximal and distal interphalangeal joints, as well as the flexor tendons and extensor compartments.ResultsA total of 35 patients were included in the RA group, including 10 males and 25 females. A total of 30 patients were included in the PsA group, including 12 males and 18 females. There were no significant differences in gender composition, age, and duration of disease between the two groups (P&gt;0.05) (Table 1). 19 (63.33%) PsA patients and 16 (45.71%) RA patients had sub-clinical hand joint synovitis. At the joint level, wrist joints were most commonly involved (23.08%), followed by MCP3 (15.38%) and DIP3 (13.46%) in PsA group. In RA group, wrist joints were most commonly involved (55.17%), followed by MCP3 (12.41%), and MCP2 (11.03%). Eight (26.67%) PsA patients and 16 (45.71%) RA patients were detected tenosynovitis. Tenosynovitis was most frequently presented at the extensor tendons in RA and at the flexor tendons in PsA patients (p&lt;0.05). The two most commonly affected were the 4th and 1st extensor compartments in RA patients, and the flexor pollicis longus and flexor digitorum profundus in PsA patients. 81 (6.80%) joint recesses in the RA and 75 (7.35%) joint recesses in PsA were detected effusion. Joint effusion was most frequently detected at radiocarpal and midcarpal joints in RA (30.86%, 25.92%, respectively). Effusion in PsA was most commonly presented at the 3rd PIP joints (26.67%), followed by radiocarpal joints (24.00%). Bone erosions were uncommon, totally 2 (6.67%) PsA patients and 3 (8.57%) RA patients were detected bone erosions.Table 1.Demographic characteristics of RA and PsA patientsRA (n=35)PsA (n=30)PFemale, n(%)25 (71.43%)18 (60.00%)0.33Age, years, mean±SD53.20±14.5054.23±13.650.77Disease duration, years, mean±SD0.72±0.370.91±0.530.07ConclusionThere are significant differences in the US findings of sub-clinical inflammation at the hand and wrist joints, such as the joint effusion and tenosynovitis, which may assist the identification between early RA and PsA. Simultaneously, it should be pointed out that there are some similarities in the joint involvement of sub-clinical synovitis between RA and PsA, physicians should take this into account in clinical work.Figure 1.Gray scale ultrasound sagittal view shows synovitis at the wrist joint in an RA patient (A) and at MCP3 in a PsA patient.

OP0135 RISK OF CARDIOVASCULAR EVENTS UNDER JANUS KINASE INHIBITORS IN PATIENTS WITH RHEUMATOID ARTHRITIS: OBSERVATIONAL DATA FROM THE GERMAN RABBIT REGISTER

BackgroundIn 2021, the European and US-American regulatory agencies EMA and FDA issued warnings about the cardiovascular (CV) safety of the Janus kinase inhibitor (JAKi) tofacitinib and required changes in labelling. These actions were based on results of the post-authorisation safety trial Oral Surveillance(1).ObjectivesTo analyse major cardiovascular events (MACE) under treatment with JAKi, tumor necrosis factor inhibitors (TNFi) or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs - bionaive) in patients with rheumatoid arthritis (RA) observed in daily rheumatological care.MethodsData from patients enrolled in the biologics register RABBIT with treatment episodes from 01/2017 - 04/2021 were included. Incidence rates (IR) of MACE per 100 patient-years (PY) with 95% confidence intervals (CI) and adjusted risk ratios (RR) were calculated for all and for high-risk patients (age ≥ 50 years and ≥ 1 CV risk factor). Poisson regression analysis was adjusted for age, sex, smoking, disease activity, prior therapies, glucocorticoids and comorbidities.ResultsStarting from 2017, 2030 JAKi, 2338 TNFi and 871 csDMARD initiations were documented. Patients with a JAKi start were slightly older, more often women and had a longer RA disease duration (Table 1). The proportion with positive autoantibodies was higher than in the TNFi and csDMARD group, the physical function was lower, and they had received more previous biologic treatments. Characteristics of high-risk patients are also given in the Table 1.Table 1.Patient characteristics at the start of a JAKi, TNFi or csDMARD.ALL PATIENTSHIGH RISK PATIENTS*JAKiTNFicsDMARDJAKiTNFicsDMARD# treatment starts2030233887112151254508Age59.9 ± 11.657.6 ± 13.059.5 ± 12.764.3 ± 8.963.5 ± 8.964.4 ± 9.2Women1573 (77.5)1707 (73.0)627 (72.0)907 (74.7)864 (68.9)355 (69.9)Disease duration12.6 ± 9.68.9 ± 8.55.7 ± 6.613.3 ± 9.99.7 ± 9.16.0 ± 7.0Rheumatoid factor/ ACPA positive1531 (79.2)1672 (74.2)548 (66.3)917 (79.7)890 (73.7)321 (66.5)# previous bDMARDs2.0 ± 1.80.7 ± 1.202.0 ± 1.80.7 ± 1.20DAS28-ESR4.2 ± 1.44.5 ± 1.44.2 ± 1.34.4 ± 1.54.7 ± 1.34.3 ± 1.3Percentage of full physical function63.3 ± 24.168.6 ± 22.472.3 ± 21.960.3 ± 24.264.4 ± 23.369.6 ± 22.7Glucocorticoids ≥10 mg/d170 (17.5)239 (21.5)49 (12.4)112 (18.6)142 (22.3)23 (10.0)BMI &gt;30 kg/m2565 (28.2)631 (27.4)271 (31.7)383 (31.8)413 (33.3)180 (36.0)Sum of comorbidities2.9 ± 2.52.6 ± 2.42.2 ± 2.23.7 ± 2.63.5 ± 2.53.1 ± 2.3Current smokers461 (26.3)617 (28.5)274 (33.5)355 (33.5)466 (39.5)202 (42.3)Previous smokers551 (31.4)692 (31.9)230 (28.1)300 (28.3)338 (28.6)114 (23.9)Values are given as mean ± standard deviation or number (percentage). *Age ≥50 years and ≥ 1 CV risk factor (hypertension, coronary heart disease, diabetes, hyperlipoproteinaemia, current smoking)In total, 28 incident MACE were reported. Patients under treatment with JAKi, TNFi and csDMARD showed comparable IR for MACE between 0.26 and 0.41 events per 100 PY (Figure 1). High-risk patients showed higher IRs. The median time under treatment was 10 months on JAKi and TNFi, and 12 months on csDMARDs. The majority of events were reported in the first year after treatment start. In the adjusted analyses, JAKi (RR 0.94 [95% CI 0.39; 2.28]) and csDMARDs (RR 0.85 [0.25; 2.88]) did not show a significantly increased risk for MACE compared with TNFi in unselected patients, and also not in high-risk patients (JAKi: RR 0.90 [0.37; 2.17]; csDMARDs: RR 0.61 [0.16; 2.28]).Figure 1.Incidence rates of MACE per 100 patient years by treatment group.ConclusionIR of MACE in patients receiving JAKi in a real-world setting was lower than the IR reported for tofacitinib in the Oral Surveillance study. We found no evidence of an increased risk of MACE with JAKi compared to TNFi, although patients in the JAKi group were older and had longer disease duration.

OP0306 IMPACT OF INFLAMMATION ON INTERSTITIAL LUNG DISEASE IN PATIENTS WITH RHEUMATOID ARTHRITIS - AN ANALYSIS OF THE GERMAN BIOLOGICS REGISTER RABBIT

BackgroundTen percent of patients with prevalent rheumatoid arthritis (RA) develop an interstitial lung disease (ILD), which is associated with higher mortality (1). A previous study identified high/moderate disease activity, but not CRP, as a risk factor for RA-ILD (2).ObjectivesTo analyse whether systemic inflammation (CRP and ESR) and/or disease activity measured with a composite score (DAS28-ESR) are associated with the occurrence of ILD in patients with RA.MethodsData from RA patients observed in the biologics register RABBIT until 10/2020 were included. Patients with incident ILD were selected as cases and matched 1:5 to controls using a modified risk-set sampling (controls had no ILD during the entire observation time). Matching criteria were age, sex, RA duration, date of enrolment and observation time. Odds ratios (OR) and 95% confidence intervals (CI) were computed by conditional logistic regression and adjusted for factors identified by a directed acyclic graph (DAG), namely smoking, rheumatoid factor (RF), chronic obstructive pulmonary disease, number of biologics until index date (date of ILD-diagnosis in cases, date after the respective observation time in controls) and mean glucocorticoid dosage (12 months prior index date). For the regression, CRP and ESR were log-transformed due to their skewed distribution, and missing values were addressed by multiple imputations (n=10).ResultsOut of 19,148 RA patients enrolled since 2001, 133 patients with incident ILD were identified. Half of the ILDs were diagnosed by computed tomography (n=67), 8% by x-ray (n=10) and in 42% the method was unknown (n=56).At baseline, cases and controls had a mean age of 61 years, 68% were female, and mean RA disease duration was 9 years. Differences were observed in smoking status (59% ever smokers in cases vs. 48% in controls), RF positivity (84% vs. 72%) and the sum of comorbidities (means 3.1 vs. 2.3).During the 12 months prior to the index date, mean values of CRP and especially of ESR were significantly higher in cases compared to controls. This difference was not observed for DAS28 (Figure 1, upper figures). Furthermore, more cases than controls were in a high inflammatory status, but not in at least moderate disease activity (Figure 1, lower figures). The adjusted regression analyses confirmed these results: CRP and ESR were significantly associated with incident ILD both at the time of diagnosis and in the 12 previous months, and results were even more pronounced with elevated CRP and ESR, which was not the case for DAS28 (Table 1).Table 1.Results of the conditional logistic regression for the risk of ILD.Crude OR (95% CI)Adjusted OR (95% CI)At index dateLog CRP1.55 (1.25 – 1.92)1.55 (1.24 – 1.94)CRP≥5 vs. CRP&lt;52.43 (1.55 – 3.81)2.41 (1.49 – 3.88)Log ESR1.56 (1.22 – 2.00)1.56 (1.21 – 2.01)ESR &gt;21 vs. ESR ≤212.12 (1.40 – 3.19)2.12 (1.37 – 3.29)DAS281.17 (1.01 – 1.35)1.16 (0.99 – 1.35)DAS28 &gt;3.2 vs. DAS28 ≤3.21.31 (0.86 – 1.99)1.32 (0.85 – 2.06)Within 12 months prior to index dateLog CRP1.41 (1.14 – 1.75)1.38 (1.09 – 1.74)CRP≥5 vs. CRP&lt;52.60 (1.59 – 4.27)2.60 (1.54 – 4.41)Log ESR1.65 (1.26 – 2.16)1.60 (1.21 – 2.12)ESR &gt;21 vs. ESR ≤212.43 (1.53 – 3.86)2.35 (1.45 – 3.81)DAS281.16 (0.99 – 1.36)1.13 (0.95 – 1.34)DAS28 &gt;3.2 vs. DAS28 ≤3.21.37 (0.82 – 2.30)1.37 (0.79 – 2.35)Figure 1. Upper Figures. Unimputed and untransformed CRP, ESR and DAS28 12 months prior to the index date as means with 95% CI, computed by mixed models with matching strata as random effects. The left y-axis refers to CRP and ESR, the right to DAS28. Lower Figures. Percentages of patients with CRP≥5, ESR&gt;21 and DAS28&gt;3.2 12 months prior to the index date.ConclusionIn contrast to other data, our analyses found that markers of systemic inflammation, but not the DAS28 composite score, are associated with the occurrence of incident ILD in patients with RA and can be predictors for the development of RA-ILD. Therefore, in a treat-to-target approach, rheumatologists should pay particular attention to controlling systemic inflammation.