Clinical evaluation of optical spectral transmission imaging for detection of disease activity in rheumatoid arthritis.

OBJECTIVE: To investigate the performance and factors of influence of optical spectral transmission (OST) imaging as a new technique for measuring joint inflammation in rheumatoid arthritis (RA). METHOD: OST was performed in 24 RA patients and 37 controls. Mann-Whitney U-test was used to assess differences in OST score between RA patients and controls. Receiver operating characteristics (ROC), linear regression and generalized estimating equations analysis were used to assess the discriminative capability of OST and the association of OST score with clinical disease parameters, ultrasound, radiographic features and cardiovascular risk parameters. RESULTS: Median OST score was higher in RA patients than in controls [16.9 (interquartile range 12.77-19.7) vs 12.11 (10.32-14.93)]. At patient level, OST score was moderately associated with ultrasound [beta 0.38 (95% CI 0.16-0.60), p = 0.001] and clinical disease activity [28-joint Disease Activity Score-C-reactive protein beta 0.30 (95% CI 0.04- 0.57), p = 0.024] in RA patients. In controls, male sex, high body mass index, and hypertension were associated with higher OST scores, while these associations were absent in RA. At joint level, the area under the ROC curve for OST score, with ultrasound or clinical swelling as reference, ranged from 0.63 to 0.70. Joint-space narrowing and malalignment were associated with higher OST joint scores, and subchondral sclerosis with lower scores. CONCLUSION: OST provides an objective measure of synovitis and correlates moderately with other examined disease activity assessment tools. Clinical patient characteristics must be considered when interpreting the results.

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

BACKGROUND: Patients 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. OBJECTIVES: To 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. METHODS: All 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. RESULTS: A 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. CONCLUSIONS: An 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.

Patient perspective on exercise intervention in rheumatoid arthritis with high risk of cardiovascular disease: a pilot qualitative study.

The objective of the study was to gain an insight into the perceptions and experiences of patients with rheumatoid arthritis and a high cardiovascular disease risk (CVD-RA) when undergoing an exercise intervention aimed at improving their cardiorespiratory fitness. This qualitative study was part of a pilot study, which investigated the effects of an exercise intervention on cardiorespiratory fitness in patients with CVD-RA. Six patients were invited to participate in face-to-face semi-structured interviews. We invited patients who completed the exercise intervention as well as patients who withdrew from the exercise intervention. The interviews were analyzed according to the method of thematic analysis. Six patients were interviewed, of whom four patients completed and two patients discontinued the exercise intervention. The mean (SD) age was 58 (9.7) years, the median disease duration was 10 years, and five patients were female. The analyses revealed seven themes that provided insight into perceptions and experiences: (1) ability to understand reasons for actions; (2) the need to be seen; (3) reaching their maximum effort; (4) experiencing their limits; (5) wanting personalized exercise therapy; (6) happy to be physically active; (7) benefits of exercise. Patients perceived that they were able to perform a cardiopulmonary exercise test with maximum effort and achieved the prescribed intensity of the exercise intervention. They also experienced an improvement in their physical activity by incorporating physical activity in their daily live. Overarching principles that re-occurred in the themes were: the need to be viewed as a person and the importance of feeling safe.

Do Disease-Modifying Anti-rheumatic Drugs and Exercise Therapy Have a Combined Effect on Disease Activity in Patients with RA? A Scoping Review.

PURPOSE OF REVIEW: In addition to disease-modifying anti-rheumatic drug (DMARD) treatment, exercise is increasingly promoted in patients with rheumatoid arthritis (RA). Although both are known to reduce disease activity, few studies have investigated the combined effects of these interventions on disease activity. The aim of this scoping review was to provide an overview of the reported evidence on whether a combined effect-i.e., a greater reduction in disease activity outcome measures-can be detected in studies where an exercise intervention was performed in addition to the DMARD treatment in patients with RA. This scoping review followed the PRISMA guidelines. A literature search was performed for exercise intervention studies in patients with RA treated with DMARDs. Studies without a non-exercise control group were excluded. Included studies reported on (components of) DAS28 and DMARD use and were assessed for methodological quality using version 1 of the Cochrane risk-of-bias tool for randomized trials. For each study, comparisons between groups (i.e., exercise + medication vs. medication only) were reported on disease activity outcome measures. Study data related to the exercise intervention, medication use, and other relevant factors were extracted to assess what may have influenced disease activity outcomes in the included studies. RECENT FINDINGS: A total of 11 studies were included of which 10 between-group studies on DAS28 components were made. The remaining one study focused on within-group comparisons only. Median duration of the exercise intervention studies was 5 months, and the median number of participants was 55. Six out of the 10 between-group studies reported no significant differences between groups in DAS28 components between exercise + medication vs. medication only. Four studies showed significant reductions in disease activity outcomes for the exercise + medication group compared with the medication-only group. Most studies were not adequately designed methodologically in order to investigate for comparisons of DAS28 components and had a high risk of multi-domain bias. Whether the simultaneous application of exercise therapy and DMARD medication in patients with RA has a combined effect on disease outcome remains unknown, due to weak methodological quality of existing studies. Future studies should focus on the combined effects by having disease activity as the primary outcome.

Efficacy of celecoxib add-on treatment for immuno-metabolic depression: Protocol of the INFLAMED double-blind placebo-controlled randomized controlled trial.

Introduction: As the role of (neuro)inflammation in depression pathophysiology is emerging, augmentation of antidepressant treatments with anti-inflammatory drugs have shown beneficial results, but not consistently across all studies. Inconsistencies may be due to depression biological and clinical heterogeneity. Immuno-Metabolic Depression (IMD) has been put forward as a form of depression characterized by the clustering of low-grade inflammation, metabolic dysregulations and atypical, energy-related symptoms (overeating, weight gain, hypersomnia, fatigue and leaden paralysis). IMD features are present in ∼30% of patients with Major Depressive Disorder (MDD). By selecting these specific patients, directly targeting inflammation may reduce depressive symptoms. Methods: and analysis INFLAMED is a double-blind randomized controlled trial. 140 MDD patients with IMD characteristics (MDD with Inventory of Depressive Symptomatology (IDS) ≥ 26, IDS atypical, energy related symptoms ≥6, C-Reactive Protein (CRP) > 1 mg/L) will receive either 400 mg celecoxib per day or matching placebo for a period of 12 weeks. Biological, physical and interview data will be collected after 2, 6 and 12 weeks of starting the intervention. Questionnaires will be sent out bi-weekly during the study period. The main study outcome is the IDS (30-item self-report) total score during 12-week follow-up. Secondary study outcomes include response, remission, adverse side effects, symptom profiles (atypical, energy-related symptoms), fatigue, food craving, sleep, anxiety symptoms, functioning, pain, and optionally, microbiome composition. Explorative analyses will be performed on the role of CRP, IL-6, TNF-α, cholesterol, triglycerides, glucose, BMI, waist and hip circumference. Ethics and dissemination: This protocol has been approved by the Medical Ethics Review Board of the Amsterdam UMC, location VUmc (2022.0015) on 2-6-2022, as well as by the competent authority in The Netherlands: CCMO, on 3-8-2022. Registration details: Trail registration numbers NCT05415397, EudraCT 2021-003850-21.

In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

Interval prolongation of etanercept in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis: a randomized controlled trial.

OBJECTIVE: The majority of patients with a rheumatic disease treated with etanercept may be overexposed. Data regarding etanercept tapering are scarce, particularly in psoriatic arthritis (PsA) and ankylosing spondylitis (AS). We compared extending the dose interval to continuation of the standard dose and studied the success rate of etanercept discontinuation. Etanercept concentrations were measured throughout the study. METHOD: 160 patients with rheumatoid arthritis (RA), PsA, or AS with sustained minimal disease activity (MDA) were enrolled in this 18-month, open-label, randomized controlled trial. The intervention group doubled the dosing interval at baseline and discontinued etanercept 6 months later. The control group continued the standard dose for 6 months and doubled the dosing-interval thereafter. The primary outcome was the proportion of patients maintaining MDA at 6 month follow-up. RESULTS: At 6 months, MDA status was maintained in 47 patients (63%) in the intervention group and 56 (74%) in the control group (p = 0.15), with comparable results in all rheumatic diseases. And median etanercept concentrations decreased from 1.50 µg/mL (interquartile range 1.06- 2.65) to 0.46 µg/mL (0.28-0.92). In total, 40% discontinued etanercept successfully with maintained MDA for at least 6 months. CONCLUSION: Etanercept tapering can be done without losing efficacy in RA, PsA, and AS patients in sustained MDA. A substantial proportion of patients could stop etanercept for at least 6 months. In many patients, low drug concentrations proved sufficient to control disease activity. However, the risk of minor and major flares is substantial, even in patients continuing standard dosing.

NT-proBNP and sRAGE levels in early rheumatoid arthritis.

OBJECTIVE: Several biomarkers of cardiovascular function are found to be increased in rheumatoid arthritis (RA), with some suggesting a relationship with disease activity and improvement with adequate anti-rheumatic treatment. Promising biomarkers include N-terminal pro-brain natriuretic peptide (NT-proBNP) and the soluble receptor form of advanced glycation end-products (sRAGE). The objective of this study was to investigate associations between NT-proBNP and sRAGE levels and markers of inflammation and disease activity in early RA patients and their changes during (effective) anti-rheumatic treatment. METHOD: Data from 342 consecutive early RA patients participating in the 'Parelsnoer' cohort were used. At baseline and after 6 months' disease activity, NT-proBNP and sRAGE levels were assessed. RESULTS: After 6 months, NT-proBNP decreased from 83 pmol/L (mean) at baseline to 69 pmol/L at follow-up (p < 0.001), while sRAGE increased from 997 pg/mL to 1125 pg/mL (p < 0.001). A larger decrease in erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was associated with larger changes in NT-proBNP and sRAGE. For every point decrease in ESR, there was a 1.7-point decrease in NT-proBNP and a 2.2-point increase in sRAGE. For CRP, these values were 1.7 and 2.7, respectively (p < 0.001). CONCLUSION: Suppressing inflammation, independently of achieving remission, increases sRAGE levels and decreases NT-proBNP levels significantly. Whether this translates into a decrease in incident cardiovascular disease remains to be elucidated.

Elevated Fab glycosylation of anti-hinge antibodies.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by systemic inflammation and the presence of anti-citrullinated protein antibodies (ACPAs), which contain remarkably high levels of Fab glycosylation. Anti-hinge antibodies (AHAs) recognize immunoglobulin G (IgG) hinge neoepitopes exposed following cleavage by inflammation-associated proteases, and are also frequently observed in RA, and at higher levels compared to healthy controls (HCs). Here, we investigated AHA specificity and levels of Fab glycosylation as potential immunological markers for RA. METHOD: AHA serum levels, specificity, and Fab glycosylation were determined for the IgG1/4-hinge cleaved by matrix metalloproteinase-3, cathepsin G, pepsin, or IdeS, using enzyme-linked immunosorbent assay and lectin affinity chromatography, in patients with early active RA (n = 69) and HCs (n = 97). RESULTS: AHA reactivity was detected for all hinge neoepitopes in both RA patients and HCs. Reactivity against CatG-IgG1-F(ab´)2s and pepsin-IgG4-F(ab´)2s was more prevalent in RA. Moreover, all AHA responses showed increased Fab glycosylation levels in both RA patients and HCs. CONCLUSIONS: AHA responses are characterized by elevated levels of Fab glycosylation and highly specific neoepitope recognition, not just in RA patients but also in HCs. These results suggest that extensive Fab glycosylation may develop in response to an inflammatory proteolytic microenvironment, but is not restricted to RA.

Does a short course of etanercept influence disease progression and radiographic changes in patients suspected of non-radiographic axial spondyloarthritis? Three -years follow- up of a placebo-controlled trial.

OBJECTIVE: To study the long-term effect of 16 weeks of etanercept treatment on disease activity and radiographic changes in patients with suspected non-radiographic axial spondyloarthritis (nr-axSpA). METHOD: Eighty patients with inflammatory back pain and suspected nr-axSpA, with a Bath Ankylosing Disease Activity Index (BASDAI) ≥ 4, received etanercept (n = 40) 25 mg twice weekly or placebo (n = 40) for 16 weeks. They were followed without treatment restrictions after 24 weeks, for up to 3 years. Comparisons were made between patients who received etanercept or placebo in the first period, and changes in BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), function, and radiographic changes in the spine [according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS)] and sacroiliac joints (Bath Ankylosing Spondylitis Radiology Index (BASRI). RESULTS: After 3 years of follow-up, 84% of the patients were diagnosed with SpA, predominantly axSpA. Biological treatment was started after 24 weeks in 30% of patients. Disease activity scores after 3 years did not reveal significant differences between the initial randomization groups in mean BASDAI scores (mean difference 0.9, 95% CI -1.1;0.7, p = 0.6) and ASDAS (mean ASDAS 0.3, 95% CI 0.6;3.1, p = 0.5). BASMI and function scores remained stable over 3 years. No differences in radiographic changes of the sacroiliac joints or spine were observed over 3 years between the two groups. CONCLUSION: A short course of etanercept in patients with suspected nr-axSpA did not affect disease activity, the chance of biological treatment, or radiographic progression after 3 years of follow-up.

Who stop telemonitoring disease activity and who adhere: a prospective cohort study of patients with inflammatory arthritis.

BACKGROUND: The use of frequent electronic patient reported outcome measures (ePRO's) enables monitoring disease activity at a distance (telemonitoring) in patients with inflammatory arthritis. However, telemonitoring studies report declining long-term adherence to reporting ePRO's, which may oppose the benefits of telemonitoring. Therefore, the objective was to investigate what factors are associated with (non-)adherence to telemonitoring with a weekly ePRO in patients with inflammatory arthritis (IA). METHODS: We performed a prospective cohort study in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) at Reade Amsterdam, The Netherlands. Patients telemonitored their disease activity weekly for 6 months with a modified Multidimensional Health Assessment Questionnaire completed in a smartphone application. The primary outcome was time to dropout, defined as ≥ 4 weeks of consecutively nonresponse. Based on literature and through expert meetings, a predefined set of 13 baseline factors were selected to assess the association with time to dropout through a multivariable Cox-regression analysis. RESULTS: A total of 220 consecutive patients were included (mean age 54, SD 12; 55% females; 99 RA, 81 PsA, and 40 AS). A total of 141 patients (64%) dropped out, with a median time to dropout of 17 weeks (IQR 9-26). Women had a significant higher chance to dropout over 6 months compared to men (HR 1.58, 95% CI 1.06-2.36). CONCLUSION: In the set of investigated factors, women stopped reporting the weekly ePRO sooner than men. Future focus group discussions will be performed to investigate the reasons for dropout, and in specific why women dropped out sooner. Trial registration This trials was prospectively registered at www.trialregister.nl (NL8414).

Exercise intervention on cardiorespiratory fitness in rheumatoid arthritis patients with high cardiovascular disease risk: a single-arm pilot study.

OBJECTIVE: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises. METHODS: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors. RESULTS: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg-1 min-1, p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors. CONCLUSION: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases. Key Points 1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention. 2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk. 3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg-1min-1 compared to the 20.9 ml.kg-1min-1 baseline mean of the RA patients without CVD risk).

The effect of anti-TNF on renal function in patients with ankylosing spondylitis: a prospective cohort study.

BACKGROUND: Biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases. Impaired renal function is a known predictor of CVD and elevated in ankylosing spondylitis (AS). OBJECTIVE: To assess the effect of anti-TNF on renal function in patients with AS and whether anti-TNF use is safe in AS patients with pre-existing risk factors for renal decline. METHOD: Biological-naïve consecutive AS patients treated with etanercept or adalimumab were prospectively followed from 2005 to 2014. Renal function was determined by calculation of the estimated glomerular filtration rate (eGFR), estimated with the abbreviated modification of diet in renal disease (MDRD) formula. The effect of anti-TNF on eGFR was analyzed using mixed model analysis. RESULTS: 211 AS patients were followed for a median of 156 (36-286) weeks. Overall mixed model analyses showed a significant decrease of eGFR over time (ß = - 0.040, p = 0.000), although this association did not remain significant after adjustment for responding to anti-TNF, alcohol use, disease duration, body mass index (BMI), C-reactive protein (CRP), and disease activity (ß = - 0.018, p = 0.094). However, patients with pre-existing risk factors for renal decline did have a significant change in eGFR over time (ß = - 0.029, p = 0.006). CONCLUSIONS: We found a significant change in eGFR over time, although this small decrease was not clinically relevant. This study further demonstrates that anti-TNF does not affect renal function in AS patients with and without existing risk factors for renal decline, which means that use of anti-TNF is safe concerning renal function in patients with AS. Key Points • Previous studies showed that biologicals, such as anti-tumor necrosis factor (anti-TNF), reduce cardiovascular disease (CVD) in patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS). • Impaired renal function is a known predictor of CVD, and also a known concern for many AS patients. • Use of anti-TNF is safe with regard to renal function in patients with AS. • The effect of anti-TNF on CVD in AS patients does not seem to be mediated by changes in renal function.

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

The RAPID3 questionnaire as a screening tool to reduce the number of outpatient clinic visits: a retrospective cohort study.

BACKGROUND: Treat-to-target strategies require frequent on-site evaluations of disease activity in patients with rheumatoid arthritis (RA), burdening patients and caregivers. However, this frequency may not be required in patients in a stable low disease activity state. The Routine Assessment of Patient Index Data 3 (RAPID3) is a reliable tool to detect such states in groups but has not been tested to reduce the frequency of on-site evaluations in individual patient care. In Reade, an outpatient rheumatology clinic, patients can complete the questionnaire online prior to consultation, and the results are directly fed into the electronic patient record. Focusing on low disease activity, we retrospectively studied the test characteristics of RAPID3 and its agreement with the DAS28 in our database of routine patient care. OBJECTIVE: To assess the test characteristics and agreement between de DAS28 and the RAPID3 in patients with RA, with a focus on the low disease activity categories. METHODS: We performed a retrospective database study with available clinical data collected as part of usual care from the electronic medical record at Reade Amsterdam. The dataset comprised RAPID3 assessments followed by a DAS28 within 2 weeks, obtained between June 2014 and March 2021. We dichotomized the disease activity categories for both the RAPID3 and DAS28 into low (remission and low disease activity) and high (moderate and high disease activity). With cutoff values of 2.0 for RAPID3 and 3.2 for DAS28, we calculated test characteristics and agreement (Cohen's kappa). RESULTS: A total of 5009 combined RAPID3 and DAS28 measurements were done at Reade in 1681 unique RA patients. The mean age was 60 years, and 76% of patients were female with a median disease duration of 4 years. Agreement was considered fair (kappa = 0.26). In total, 1426 (28%) of the RAPID3 measurements were classified as low and could be potentially targeted to skip their consultations. The sensitivity to detect low disease activity was 0.39, specificity was 0.93, and the positive predictive value was 0.92. CONCLUSION: We showed that when the RAPID3 classifies a patient into low disease activity state, the accuracy is 92%. Of all consultations, 28% could possibly be postponed following the screening with RAPID3.

Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study.

OBJECTIVE: To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. METHOD: Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. RESULTS: Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (ß = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). CONCLUSION: Female AS patients show a lower response to TNFi and a higher disease activity compared to men.

Aortic root diameter is associated with HLA-B27: identifying the patient with ankylosing spondylitis at risk for aortic valve regurgitation.

To assess the association between the aortic root diameter in HLA-B27 positive (+) and HLA-B27 negative (-) ankylosing spondylitis (AS) patients from the CARDAS cohort. The CARDAS study is a cross-sectional study in AS patients between 50 and 75 years who were recruited from a large rheumatology outpatient clinic. Patients underwent cardiovascular screening including echocardiography, with 2D, spectral, and color flow Doppler measurements. The aortic root was measured at sinuses of Valsalva during diastole. The aortic root diameter was adjusted for body surface area (BSA) (aortic root index, cm/m2). 193 Consecutive AS patients were included of whom 158 (82%) were HLA-B27 positive. The aortic root index was significantly higher in HLA-B27 + patients compared to HLA-B27- patients, respectively, 1.76 cm ± 0.21 vs. 1.64 cm ± 0.14, p < 0.001. No difference was seen in the prevalence of aortic valve regurgitation (AVR), p = 0.8. Regression analysis showed a significant association between HLA-B27 and aortic root index corrected for age, sex and cardiovascular risk factors (ß 0.091, 95% CI 0.015-0.168, p = 0.02). Especially, male HLA-B27 + patients had a significantly increased aortic root index compared to male HLA-B27- AS patients, respectively, 1.76 cm (1.63-1.88) and 1.59 cm (1.53-1.68), p < 0.001. We found an increased aortic root index in elderly HLA-B27 + AS patients compared to HLA-B27- AS patients, especially in male patients. No difference was seen in the prevalence of AVR. However, as AVR can be progressive, echocardiographic monitoring in elderly male HLA-B27 + AS might be considered.

Cardiorespiratory fitness and physical activity in people who have rheumatoid arthritis at an increased risk of cardiovascular disease: a cross-sectional study.

Lower cardiorespiratory fitness (CRF) and physical activity (PA) associate with higher cardiovascular disease (CVD) risk, but the relationship between CRF and PA in people who have rheumatoid arthritis (RA) at an increased CVD risk (CVD-RA) is not known. The objectives of this study were to determine the levels of CRF and PA in people who have CVD-RA and to investigate the association of CRF with PA in people who have CVD-RA. A total of 24 consecutive patients (19 women) with CVD-RA (> 4% for 10-year risk of fatal CVD development as calculated using the Systematic Coronary Risk Evaluation)-were included in the study. CRF was assessed with a graded maximal exercise test determining maximal oxygen uptake (VO2max). PA was assessed with an accelerometer to determine the amount of step count, sedentary, light and moderate-to-vigorous physical activity (MVPA) minutes per day. Mean age of patients was 65.3 ± 8.3 years. CRF mean values were 16.3 ± 1.2 ml·kg-1 min-1, mean step count per day was 6033 ± 2256, and the mean MVPA time was 16.7 min per day. Significant positive associations were found for CRF with step count (B = 0.001, P = 0.01) and MVPA time (B = 0.15, P = 0.02); a negative association was found for CRF with sedentary time (B = - 0.02, P = 0.03). CRF is low and is associated with step count, sedentary time and MVPA time in people who have RA at an increased CVD risk.

Accuracy of an algorithm to identify rheumatoid arthritis in the Longitudinal Ageing Study Amsterdam population: a validation study.

Objective: In view of global ageing and the scarcity of knowledge about disease determinants in older individuals with rheumatoid arthritis (RA), an algorithm with optimal diagnostic accuracy was developed to identify RA patients in the Longitudinal Ageing Study Amsterdam (LASA).Method: Four case ascertainment algorithms were constructed and assessed for validity in LASA, an ongoing cohort study (≥ 55 years) representing the general older population of the Netherlands. Data sources used to identify the diagnosis RA were: self-reported morbidity, specialist diagnosis, and medication. A validation subsample of LASA participants was taken to verify RA diagnosis by a standard procedure using a checklist.Results: Data from 272/300 (91%) participants were verified. Four algorithms were developed: 'treatment', 'diagnosis', 'treatment or diagnosis', and 'treatment and diagnosis'. The algorithm 'treatment and diagnosis' showed the best measurement properties: specificity 100%, positive predictive value 100%, and area under the receiver operating characteristics curve 0.72. Applying this algorithm in the LASA sample (mean age 71 years) revealed a prevalence of RA of 1.0% (19/1908 participants).Conclusion: An algorithm for RA identification in the LASA population was developed, with high diagnostic accuracy. It provides an accurate tool to identify older adults with RA in LASA and, after validation, may be applicable in other large population-based studies.

Coexistent subclinical hypothyroidism is associated with an increased risk of new cardiovascular events in rheumatoid arthritis: an explorative study.

Objective: Autoimmune thyroid disease often coexists with rheumatoid arthritis (RA) and is associated with elevated cardiovascular (CV) risk. However, studies in RA patients are scarce. Our aim was to investigate whether autoimmune thyroid disease increases the risk of new cardiovascular disease (CVD) in RA.Method: Thyroid-stimulating hormone (TSH) and serum free thyroxine (FT4) were assessed in 323 RA patients participating in an ongoing prospective cohort study designed to assess CV risk factors, morbidity, and mortality. Cox proportional hazard models were used to calculate hazard ratios (HRs) for new CVD and adjusted for age, gender, smoking, prevalent CVD, thyroxine replacement therapy, and RA duration.Results: Of the 323 participants, 65.3% were female, and mean ± sd age was 63 ± 7 years. At baseline, 8.1% were hypothyroid (n = 26, 16 clinical, 10 subclinical), 6.8% hyperthyroid (n = 22, 13 clinical, 9 subclinical), and 85.1% (n = 275) euthyroid. A new CV event developed in 94 patients (29.1%) during follow-up. Compared to euthyroid patients, the HR adjusted for age, gender, and prevalent CVD was 2.83 [95% confidence interval (CI) 1.13-7.09; p = 0.026] for subclinical hypothyroidism. Further adjustment for smoking, thyroxine replacement therapy, and RA duration resulted in an HR of 3.0 (95% CI 1.19-7.54; p = 0.02) for CV events in patients with subclinical hypothyroidism.Conclusion: There was no difference in CVD between RA patients with hypothyroidism and hyperthyroidism versus euthyroid patients. Coexistence of subclinical hypothyroidism with RA is associated with a higher occurrence of new CV events. Treatment trials are needed to determine whether thyroxine supplementation can further improve CV outcome in these patients.