Can rheumatologists unequivocally diagnose axial spondyloarthritis in patients with chronic back pain of less than 2 years duration? Primary outcome of the 2-year SPondyloArthritis Caught Early (SPACE) cohort.

OBJECTIVES: To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. METHODS: We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (≥3 months, ≤2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). MAIN OUTCOME: axSpA diagnosis with LoC≥7 (d-axSpA) at 2y. RESULTS: In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. CONCLUSION: A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients.

Patients with axial spondyloarthritis reported willingness to use remote care and showed high adherence to electronic patient-reported outcome measures: an 18-month observational study.

Remote monitoring using electronic patient reported outcomes (ePROs) in axial spondyloarthritis (axSpA) may improve self-management and reduce the need for consultations. However, knowledge regarding patients' willingness to use remote care and adherence to reporting ePROs is scarce. The objective of this study was to assess axSpA patients' willingness to use remote care and adherence to reporting of ePROs. The study was part of a three-armed randomized controlled trial testing digital follow-up strategies (The ReMonit study, NCT: 05031767). AxSpA patients in low disease activity were randomized to usual care, remote monitoring, or patient-initiated care. Demographics, clinical data, and patients' willingness to use remote care were collected at baseline. EPROs were reported either monthly or quarterly by the remote monitoring- and patient-initiated care group over 18 months, respectively. Adherence to reporting was calculated as number of ePROs completed divided by the total number requested. Mixed model logistic regression was utilized to assess factors associated with adherence to reporting of ePROs. In total 242 patients (median age 43 years, 75% males) were included. The majority (96%) reported high willingness to use remote care. Adherence to reporting ePROs remained high over 18 months by remote monitoring and patient-initiated care groups [median (IQR): 88% (77-100) vs. 83% (66-100)]. No patient characteristics were significantly associated with adherence to reporting of ePROs. The high degree of willingness and adherence to reporting ePROs over time indicates that the majority of axSpA patients with low disease activity are motivated to use remote care.

Cardiovascular organ damage in relation to hypertension status in patients with ankylosing spondylitis.

PURPOSE: Hypertension is a major cardiovascular (CV) risk factor in ankylosing spondylitis (AS) patients. Less is known about the prevalence of CV organ damage in relation to hypertension status in AS patients. MATERIALS AND METHODS: CV organ damage was assessed by echocardiography, carotid ultrasound and pulse wave velocity (PWV) by applanation tonometry in 126 AS patients (mean age 49 ± 12 years, 39% women) and 71 normotensive controls (mean age 47 ± 11 years, 52% women). CV organ damage was defined as presence of abnormal left ventricular (LV) geometry, LV diastolic dysfunction, left atrial (LA) dilatation, carotid plaque or high pulse wave velocity (PWV). RESULTS: Thirty-four percent of AS patients had hypertension. AS patients with hypertension were older and had higher C-reactive protein (CRP) levels compared to AS patients without hypertension and controls (p < 0.05). The prevalence of CV organ damage was 84% in AS patients with hypertension, 29% in AS patients without hypertension and 30% in controls (p < 0.001). In multivariable logistic regression analyses, having hypertension was associated with a fourfold increased risk of CV organ damage independent of age, presence of AS, gender, body mass index, CRP, and cholesterol (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.53 to 13.61, p = 0.006). In AS patients, presence of hypertension was the only covariable significantly associated with presence of CV organ damage (OR 4.40, 95% CI 1.40 to 13.84, p = 0.011). CONCLUSIONS: CV organ damage in AS was strongly associated with hypertension, pointing to the importance of guideline-based hypertension management in AS patients.

What is the context? Ankylosing spondylitis (AS) is an inflammatory disease primarily affecting the spine. Patients with AS have increased risk for cardiovascular disease. High blood pressure (hypertension) is both very common in AS patients, and a major risk factor for developing cardiovascular disease. Hypertension leads to structural and functional changes in the heart and arteries, referred to as cardiovascular organ damage. However, little is known about the prevalence of cardiovascular organ damage in AS patients with hypertension.What is new? Using ultrasound and tonometry, we assessed organ damage in the heart and arteries in AS patients with hypertension and compared them to AS patients with normal blood pressure as well as a group of healthy controls. We found that 84% of the AS patients with hypertension had cardiovascular organ damage, compared to 29% of AS patients with normal blood pressure and 30% of controls. Independent of other risk factors, hypertension was associated with a fourfold increased risk of cardiovascular organ damage in AS patients.What is the impact? These findings are important because cardiovascular organ damage is potentially reversible with treatment. Our results underline the significance of guideline-directed hypertension management in AS patients to reduce cardiovascular disease.

Willingness, perceived facilitators and barriers to use remote care among healthcare professionals - a cross-sectional study.

BACKGROUND: Remote care has the potential of improving access to timely care for people with inflammatory joint diseases (IJD), but there is limited knowledge on how this approach is regarded by healthcare professionals (HCP). This study aimed to examine willingness, perceived facilitators, and barriers to use remote care among HCP. METHODS: Employees at 20 rheumatology departments in Norway received a digital survey containing 16 statements regarding willingness, perceived facilitators and barriers to use remote care. Statements were scored using numeric rating scales (NRS, 0-10, 10 = strongly agree), and analysed in linear regression models. Open-ended responses with participant-defined facilitators and barriers were analysed using qualitative manifest analysis. RESULTS: A total of 130 participants from 17 departments completed the survey. The majority of participants were 45 years or older (n = 84, 54%), 54 (42%) were medical doctors, 48 (37%) nurses, and 27 (21%) were allied healthcare professionals, clinical leaders, or secretaries. A high willingness to use remote care was observed (median NRS: 9, IQR 8-10). The facilitator statement with the highest score was that patients save time and costs by using remote care, whereas the barrier statement with the highest score was the lack of physical examination. Willingness to use remote care was positively associated with the belief that patients wish to use it (ß: 0.18, 95% CI: 0.00, 0.34), that patients in remission need less hospital visits (ß: 0.30, 95% CI: 0.16, 0.43), and if remote care is widely adopted by co-workers (ß: 0.27, 95% CI: 0.15, 0.39). Willingness was negatively associated with mistrust in the technical aspects of remote care (ß: -0.26, 95% CI:-0.40, -0.11), and lack of physical examination (ß: -0.24, 95% CI: -0.43, -0.06). The open-ended responses showed that technological equipment, eligible patients, user-friendly software, adequate training and work flow could be facilitators, but also that lack of these factors were considered barriers to use remote care. CONCLUSION: This study showed that HCP have a high willingness to use remote care, and provides important new knowledge on perceived facilitators and barriers among HCP relevant for implementation of remote care for eligible patients with IJD.

High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients.

BACKGROUND: Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown. OBJECTIVE: To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA). METHOD: Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0-10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study. RESULTS: 97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: -0.6 [-0.8 to -0.3], p<0.001 and BASDAI: -1.2 [-1.8 to -0.7], p<0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health. CONCLUSION: High intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients' function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA. TRIAL REGISTRATION NUMBER: NCT02356874.

CRP and ASDAS are associated with future elevated arterial stiffness, a risk marker of cardiovascular disease, in patients with ankylosing spondylitis: results after 5-year follow-up.

OBJECTIVE: To identify factors associated with elevated arterial stiffness in a 5-year follow-up of patients with ankylosing spondylitis (AS). METHODS: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath AS disease activity index (BASDAI) and AS disease activity score (ASDAS) were recorded in 2003, and arterial stiffness (Augmentation Index (AIx) and pulse wave velocity (PWV)) in 2008/2009. Patients were grouped into quartiles according to baseline CRP, ESR and BASDAI and four ASDAS groups. Trend analyses were performed using ANCOVA (AIx/PWV as dependent variable) with separate models for CRP, ESR, BASDAI and ASDAS (age and gender adjusted). Independent predictors of future AIx and PWV levels were identified in multivariate linear regression models. RESULTS: In total, 85 patients participated. Increasing baseline values of CRP, ESR and ASDAS were associated with elevated AIx on follow-up (p(trend) 0.01, 0.05 and 0.04, respectively). Similar non-significant patterns were seen for PWV. In the multivariate analyses, baseline CRP and ASDAS were independently associated with future elevated AIx (p=0.03 and0.02, respectively). In the multivariate PWV model, results for CRP and ASDAS were non-significant. CONCLUSIONS: Baseline CRP and ASDAS were associated with future elevated arterial stiffness measured as AIx, supporting that disease activity is related to future risk of cardiovascular disease in patients with AS.

Follow-Up of Patients With Axial Spondyloarthritis in Specialist Health Care With Remote Monitoring and Self-Monitoring Compared With Regular Face-to-Face Follow-Up Visits (the ReMonit Study): Protocol for a Randomized, Controlled Open-Label Noninferiority Trial.

BACKGROUND: Patients with chronic inflammatory joint diseases such as axial spondyloarthritis have traditionally received regular follow-up in specialist health care to maintain low disease activity. The follow-up has been organized as prescheduled face-to-face visits, which are time-consuming for both patients and health care professionals. Technology has enabled the remote monitoring of disease activity, allowing patients to self-monitor their disease and contact health care professionals when needed. Remote monitoring or self-monitoring may provide a more personalized follow-up, but there is limited research on how these follow-up strategies perform in maintaining low disease activity, patient satisfaction, safety, and cost-effectiveness. OBJECTIVE: The Remote Monitoring in Axial Spondyloarthritis (ReMonit) study aimed to assess the effectiveness of digital remote monitoring and self-monitoring in maintaining low disease activity in patients with axial spondyloarthritis. METHODS: The ReMonit study is a 3-armed, single-site, randomized, controlled, open-label noninferiority trial including patients with axial spondyloarthritis with low disease activity (Ankylosing Spondylitis Disease Activity Score <2.1) and on stable treatment with a tumor necrosis factor inhibitor. Participants were randomized 1:1:1 to arm A (usual care, face-to-face visits every sixth month), arm B (remote monitoring, monthly digital registration of patient-reported outcomes), or arm C (patient-initiated care, self-monitoring, no planned visits during the study period). The primary end point was disease activity measured with the Ankylosing Spondylitis Disease Activity Score, evaluated at 6, 12, and 18 months. We aimed to include 240 patients, 80 in each arm. Secondary end points included other measures of disease activity, patient satisfaction, safety, and cost-effectiveness. RESULTS: The project is funded by the South-Eastern Norway Regional Health Authority and Centre for the treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Norway. Enrollment started in September 2021 and was completed with 242 patients by June 2022. The data collection will be completed in December 2023. CONCLUSIONS: To our knowledge, this trial will be among the first to evaluate the effectiveness, safety, and cost-effectiveness of remote digital monitoring and self-monitoring of patients with axial spondyloarthritis compared with usual care. Hence, the ReMonit study will contribute important knowledge to personalized follow-up strategies for patients with axial spondyloarthritis. These results may also be relevant for other patient groups with inflammatory joint diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05031767; hpps://www.clinicaltrials.gov/study/NCT05031767. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52872.

High-Intensity Exercise Improves Fatigue, Sleep, and Mood in Patients With Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Although exercise is recommended in the treatment of axial spondyloarthritis (axSpa), the focus has been on flexibility, and the effect of high-intensity exercises is unknown. The purpose of this study was to investigate the effect of high-intensity exercises on fatigue, sleep, and mood in patients with axSpA. METHODS: In this secondary analysis of a randomized controlled trial, participants were recruited from outpatient clinics at 4 hospitals in Scandinavia. A total of 100 patients with axSpA were randomized to either an exercise group (n = 50) or a control group (n = 50). High-intensity exercise was provided 3 times per week for 3 months and supervised by a physical therapist. The controls received no intervention. Measurements were self-reported at baseline, 3 months, and 12 months: fatigue, using the Fatigue Severity Scale (range = 0-7, 7 = worst, ≥5 = severe); vitality, using the RAND 36-item short-form health survey (SF-36, range = 0-100, 100 = best); sleep, using the Pittsburgh Sleep Quality Index (range = 0-21, 21 = worst, >5 = poor quality); mood, using the General Health Questionnaire 12 (range = 0-36, 36 = worst); and general health, using the EUROQoL (range = 0-100, 100 = best). RESULTS: A total of 38 participants (76%) in the exercise group followed ≥80% of the exercise protocol. At 3 months, there was a significant beneficial effect on fatigue (mean group differences = -0.4, 95% CI = -0.7 to -0.1), vitality (5.0, 95% CI = 1.1 to 10.5), mood (-2, 95% CI = -3.7 to -0.04), and general health (9.0, 95% CI = 3.3 to 14.7) but no effect on sleep (-1.1, 95% CI = -2.1 to 0.2). Compared with the control group, the exercise group had a reduced rate of severe fatigue and poor sleep. No differences were seen between the groups at 12 months. CONCLUSIONS: A 3-month exercise program had a beneficial effect on fatigue, sleep, mood, and general health in patients with axSpA at the end of the intervention; however, no long-term effects were seen. IMPACT: High-intensity cardiorespiratory and strength exercises should be considered as important in exercise programs for patients with axSpA.

Ankylosing Spondylitis Is Associated with Increased Prevalence of Left Ventricular Hypertrophy.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with increased risk for cardiovascular disease (CVD). Left ventricular (LV) hypertrophy is a strong precursor for clinical CVD. The aim of our study was to assess whether having AS was associated with increased prevalence of LV hypertrophy. METHODS: Clinical and echocardiographic data from 139 AS patients and 126 age- and sex-matched controls was used. LV mass was calculated according to guidelines and indexed to height2.7. LV hypertrophy was considered present if LV mass index was > 49.2 g/m2.7 in men and > 46.7 g/m2.7 in women. RESULTS: Patients with AS were on average 49 ± 12 years old, and 60% were men. The prevalence of hypertension (HTN; 35% vs 41%) and diabetes (5% vs 2%) was similar among patients and controls, while patients with AS had higher serum C-reactive protein level (CRP; p < 0.001). The prevalence of LV hypertrophy was higher in patients with AS compared to controls (15% vs 6%, p = 0.01). In multivariable logistic regression analysis, having AS was associated with OR 6.3 (95% CI 2.1-19.3, p = 0.001) of having LV hypertrophy independent of the presence of HTN, diabetes, and obesity. In multivariable linear regression analyses, having AS was also associated with higher LV mass (ß 0.15, p = 0.007) after adjusting for CVD risk factors including sex, body mass index, systolic blood pressure, diabetes, and serum CRP (multiple R2 = 0.41, p < 0.001). CONCLUSION: Having AS was associated with increased prevalence of LV hypertrophy independent of CVD risk factors. This finding strengthens the indication for thorough CVD risk assessment in patients with AS.

Associations Between Cardiorespiratory Fitness and Arterial Stiffness in Ankylosing Spondylitis: A Cross-sectional Study.

OBJECTIVE: To assess associations between cardiorespiratory fitness (CRF), measured as peak oxygen uptake (VO2peak), and cardiovascular disease (CVD) risk, measured by arterial stiffness, in patients with ankylosing spondylitis (AS). METHODS: VO2peak was assessed by a maximal walking test on a treadmill. Arterial stiffness was measured noninvasively (Sphygmocor apparatus). Cross-sectional associations between VO2peak and arterial stiffness were analyzed using backward multivariable linear regression. RESULTS: Among 118 participating patients, there were significant inverse associations between VO2peak and arterial stiffness, independent of traditional CVD risk factors and measures of disease activity. CONCLUSION: Reduced CRF may be related to increased risk of CVD in AS.

Frequency of Impaired Spinal Mobility in Patients with Chronic Back Pain Compared to Patients with Early Axial Spondyloarthritis.

OBJECTIVE: To examine the frequency of impaired spinal mobility in patients with chronic back pain of short duration and to compare it with the frequency of impaired spinal mobility in patients with axial spondyloarthritis (axSpA), possible SpA, and no SpA. METHODS: The SpondyloArthritis Caught Early (SPACE) cohort includes patients with chronic back pain (≥ 3 mos, ≤ 2 yrs, onset < 45 yrs). Spinal mobility was assessed with lateral spinal flexion, chest expansion, cervical rotation, occiput-to-wall distance, and lumbar flexion. Hip mobility was assessed with intermalleolar distance. Mobility measures were defined as impaired if below the 5th percentile reference curve from general population, adjusted for age and height when appropriate. Proportions of patients categorized with impaired mobility were examined with chi square. RESULTS: In total, 393 patients with chronic back pain were included: 142 axSpA, 140 possible SpA, and 111 no SpA. Impairment in ≥ 1 mobility measure was present in 66% of all patients. The most frequently impaired mobility measure was lateral spinal flexion (40%), followed by chest expansion (22%), cervical rotation (18%), intermalleolar distance (17%), lumbar flexion (15%), and occiput-to-wall distance (11%). No statistically significant differences in proportion of patients with impaired spinal mobility were found between patients with axSpA and the other subgroups in any of the tests. CONCLUSION: Two out of 3 patients with chronic back pain of short duration had impaired spinal mobility compared to the general population. Impaired spinal mobility occurs as often in patients with early axSpA as in other forms of chronic back pain.

Magnetic Resonance Imaging of the Sacroiliac Joints Indicating Sacroiliitis According to the Assessment of SpondyloArthritis international Society Definition in Healthy Individuals, Runners, and Women With Postpartum Back Pain.

OBJECTIVE: To compare magnetic resonance images (MRIs) of the sacroiliac (SI) joints of healthy subjects and individuals with known mechanical strain acting upon the SI joints to those of patients with axial spondyloarthritis (SpA) and patients with chronic back pain. METHODS: Three readers who had received standardized training and were blinded with regard to study group randomly scored MRIs of the SI joints of 172 subjects, including 47 healthy individuals without current or past back pain, 47 axial SpA patients from the Spondyloarthritis Caught Early (SPACE) cohort (with a previous MRI confirmed positive for sacroiliitis), 47 controls with chronic back pain (irrespective of MRI results) from the SPACE cohort, 7 women with postpartum back pain, and 24 frequent runners. MRIs were scored according to the Assessment of SpondyloArthritis international Society (ASAS) definition and Spondyloarthritis Research Consortium of Canada (SPARCC) index. RESULTS: Of the 47 healthy volunteers, 11 (23.4%) had an MRI positive for sacroiliitis, compared to 43 (91.5%) of 47 axial SpA patients and 3 (6.4%) of 47 patients with chronic back pain. Three (12.5%) of the 24 runners and 4 (57.1%) of the 7 women with postpartum back pain had a positive MRI. Using a SPARCC cutoff of ≥2 for positivity, 12 (25.5%) of 47 healthy volunteers, 46 (97.9%) of 47 positive axial SpA patients, 5 (10.6%) of 47 controls with chronic back pain, 4 (16.7%) of 24 runners, and 4 (57.1%) of 7 women with postpartum back pain had positive MRIs. Deep bone marrow edema (BME) lesions were not found in healthy volunteers, patients with chronic back pain, or runners, but were found in 42 (89.4%) of 47 positive axial SpA patients and in 1 (14.3%) of 7 women with postpartum back pain. CONCLUSION: A substantial proportion of healthy individuals without current or past back pain has an MRI positive for sacroiliitis according to the ASAS definition. Deep (extensive) BME lesions are almost exclusively found in axial SpA patients.

Is the current ASAS expert definition of a positive family history useful in identifying axial spondyloarthritis? Results from the SPACE and DESIR cohorts.

BACKGROUND: The Assessment of SpondyloArthritis international Society (ASAS) definition of a positive family history (PFH) of spondyloarthritis (SpA) includes the following diseases in first- or second-degree relatives: ankylosing spondylitis (AS), acute anterior uveitis (AAU), reactive arthritis (ReA), inflammatory bowel disease (IBD), and psoriasis. However, it is not known if a PFH for each of these diseases contributes to making a diagnosis of axSpA, sacroiliitis on imaging, or fulfilling the ASAS criteria in patients presenting with chronic back pain (CBP). Therefore, the aim of this study was to assess which SpA diseases in family members are associated with human leukocyte antigen B27 (HLA-B27) and axial spondyloarthritis (axSpA) in CBP patients. METHODS: CBP patients suspected of axSpA from the SPACE (n = 438) and the DESIR (n = 647) cohort were asked about the presence of SpA diseases in first- or second-degree relatives (AS, AAU, ReA, IBD, and psoriasis). The associations between a PFH and HLA-B27, sacroiliitis on imaging (magnetic resonance imaging (MRI) or radiographs), axSpA diagnosis, and ASAS classification in CBP patients were assessed. RESULTS: In the SPACE and the DESIR cohort, a PFH of AS (odds ratio (OR) 5.9 (95% confidence interval (CI) 3.5-9.9), and OR 3.3 (95% CI 2.1-5.2)) and a PFH of AAU (OR 9.8 (95% CI 3.3-28.9) and OR 21.6 (95% CI 2.9-160.1)) were significantly associated with presence of HLA-B27. Furthermore, in both cohorts a PFH of AS and a PFH of AAU were positively associated with fulfilment of the ASAS criteria, but not with sacroiliitis on imaging. In SPACE but not in DESIR a PFH of AAU was positively associated with axSpA diagnosis. In both cohorts a PFH of ReA, IBD, or psoriasis was not positively associated with HLA-B27 positivity, sacroiliitis on imaging, axSpA diagnosis, or meeting the ASAS criteria for axSpA. CONCLUSIONS: In our cohorts, a PFH of AS or AAU is useful for case-finding of axSpA as this is correlated with HLA-B27 carriership. However, as a PFH of ReA, IBD, or psoriasis does not contribute to identifying axSpA in CBP patients, these data suggest that the widely used ASAS definition of a PFH of SpA should be updated. TRIAL REGISTRATION: Trial registration number, NCT01648907 . Registered on 20 July 2012.

Predictive Value of Arterial Stiffness and Subclinical Carotid Atherosclerosis for Cardiovascular Disease in Patients with Rheumatoid Arthritis.

OBJECTIVE: We evaluated the predictive value of these vascular biomarkers for cardiovascular disease (CVD) events in patients with rheumatoid arthritis (RA): aortic pulse wave velocity (aPWV), augmentation index (AIx), carotid intima-media thickness (cIMT), and carotid plaques (CP). They are often used as risk markers for CVD. METHODS: In 2007, 138 patients with RA underwent clinical examination, laboratory tests, blood pressure testing, and vascular biomarker measurements. Occurrence of CVD events was recorded in 2013. Predictive values were assessed in Kaplan-Meier plots, log-rank, and crude and adjusted Cox proportional hazard (PH) regression analyses. RESULTS: Baseline median age and disease duration was 59.0 years and 17.0 years, respectively, and 76.1% were women. CVD events occurred in 10 patients (7.2%) during a mean followup of 5.4 years. Compared with patients with low aPWV, AIx, cIMT, and without CP, patients with high aPWV (p < 0.001), high AIx (p = 0.04), high cIMT (p = 0.01), and CP (p < 0.005) at baseline experienced more CVD events. In crude Cox PH regression analyses, aPWV (p < 0.001), cIMT (p < 0.001), age (p = 0.01), statin (p = 0.01), and corticosteroid use (p = 0.01) were predictive of CVD events, while AIx was nonsignificant (p = 0.19). The Cox PH regression estimates for vascular biomarkers were not significantly altered when adjusting individually for demographic variables, traditional CVD risk factors, RA disease-related variables, or medication. All patients who developed CVD had CP at baseline. CONCLUSION: CP, aPWV, and cIMT were predictive of CVD events in this cohort of patients with RA. Future studies are warranted to examine the additive value of arterial stiffness and carotid atherosclerosis markers in CVD risk algorithms. Regional Ethical Committee approval numbers 2009/1582 and 2009/1583.

The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Risk Factors: A 12-Month Longitudinal Study in Rheumatoid Arthritis Patients Treated with Rituximab, Abatacept and Tociliziumab.

OBJECTIVES: To assess whether treatment with one of three novel biological DMARDs; rituximab, abatacept or tocilizumab reduce cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: This is an open, observational and prospective study with visits at baseline, 3, 6, and 12 months. Patients were assigned to receive rituximab, abatacept or tocilizumab according to clinical indications assessed by an independent rheumatologist. Disease activity was quantified by the disease activity score (DAS28) and extensive ultrasonography. CVD risk was assessed by total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), blood pressure and arterial stiffness measurements [pulse wave velocity (PWV) and augmentation index (AIx)]. Within group change in disease activity and CVD risk over 3 months was explored using paired samples bivariate tests. Predictors of change in CVD risk at 3 months were identified in linear regression models. Changes in CVD risk markers over the 12- month follow-up in patients receiving rituximab were assessed by mixed models repeated analyses. RESULTS: 24 patients on rituximab, 5 on abatacept and 7 on tocilizumab were included. At 3 months PWV was significantly reduced in the tocilizumab group only, but at 12 months rituximab patients showed a significant reduction in PWV. Reduced inflammation at 3 months was associated with increased TC and HDL-c in the entire cohort. CONCLUSION: Treatment with tocilizumab and rituximab reduces PWV, a marker of CVD risk, in patients with RA.

Disease activity in ankylosing spondylitis and associations to markers of vascular pathology and traditional cardiovascular disease risk factors: a cross-sectional study.

OBJECTIVE: To compare the risk of cardiovascular disease (CVD) in ankylosing spondylitis (AS) and population controls, and to examine the associations between disease activity and CVD risk. METHODS: A cross-sectional study was done of patients with AS grouped according to Ankylosing Spondylitis Disease Activity Score (ASDAS) into ASDAS-high and ASDAS-low. Markers of vascular pathology, impaired endothelial function [asymmetric dimethylarginine (ADMA)], and arterial stiffness [augmentation index (AIx) and pulse wave velocity (PWV)], and traditional CVD risk factors [blood pressure, lipids, body mass index (BMI), CVD risk scores] were compared between AS and controls as well as across ASDAS-high versus ASDAS-low versus controls using ANCOVA analyses. RESULTS: Altogether, 151 patients with AS and 134 controls participated. Patients had elevated ADMA (µmol/l) and AIx (%) compared to controls: mean difference (95% CI): 0.05 (0.03, 0.07), p < 0.001 and 2.6 (0.8, 4.3), p = 0.01, respectively. AIx increased with higher ASDAS level, p(trend) < 0.04. There were no significant group differences of PWV. BMI was higher in ASDAS-high compared to ASDAS-low (p = 0.02). Total cholesterol was lower in AS compared to controls, and lower with higher ASDAS, p(trend) = 0.02. CVD risk scores were similar across groups except for Reynolds Risk Score, where the ASDAS-high group had a significantly higher score, compared to both ASDAS-low and controls. CONCLUSION: Elevated ADMA and AIx in AS support a higher CVD risk in AS. Elevated AIx and BMI in AS with high ASDAS indicate an association between disease activity and CVD risk. Lower total cholesterol in AS may contribute to underestimation of CVD risk.

Uveitis is associated with hypertension and atherosclerosis in patients with ankylosing spondylitis: a cross-sectional study.

OBJECTIVES: Uveitis is the most common extra-articular manifestation in patients with ankylosing spondylitis (AS), but the literature describing AS patients with a history of uveitis is limited. The objective was to examine if a history of uveitis in patients with AS is associated with increased disease activity and functional impairment and to investigate whether uveitis is associated with an increased frequency of cardiovascular comorbidities, defined here as hypertension and atherosclerosis. METHODS: Data were recorded cross-sectionally through patient interviews, blood samples, clinical examination, and questionnaires. Carotid plaques were identified by ultrasonography. AS disease activity and function were compared across categories of uveitis using ANCOVA analyses. Associations between uveitis and hypertension and atherosclerosis [atherosclerotic cardiovascular disease (CVD) and/or carotid plaque] were analyzed in multivariate logistic regression models. RESULTS: Of 159 patients with AS (61.6% male, mean age 50.5 years), 84 (52.8%) had experienced one or more episodes of uveitis. AS disease activity was higher in patients with a history of uveitis, statistically significant for functional impairment [Bath AS Functional Index (BASFI)] [mean difference (95% CI)] lnBASFI = 0.2 (0.0-0.3), p = 0.05. Patients with uveitis had an increased odds ratio [OR (95% CI)] for hypertension [3.29 (1.29-8.41), p = 0.01] and atherosclerosis [2.57 (1.15-5.72), p = 0.02]. CONCLUSIONS: AS patients with a history of uveitis had non-significantly higher disease activity and significantly higher functional impairment. A history of uveitis was associated with hypertension as well as atherosclerosis. These results may be important in identifying AS patients with elevated risk of CVD but should be confirmed in longitudinal cohorts.

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

BACKGROUND: Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. METHODS: In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals. RESULTS: Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred. CONCLUSION: High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01436942.