Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity.

BACKGROUND: To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA). METHODS: This study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995-2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. RESULTS: A first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17-1.80 and 1.51; 95% CI 1.18-1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99-1.74 and 1.35, 95% CI 0.99-1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10-6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD. CONCLUSION: COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.

Incident Gout: Risk of Death and Cause-Specific Mortality in Western Sweden: A Prospective, Controlled Inception Cohort Study.

Background: Excess mortality in gout has been attributed to cardiovascular diseases (CVD). Considering the decline in CVD mortality in the general population, we wanted to evaluate overall mortality in gout and cause-specific contributions to mortality beyond CVD and temporal trends. Methods: All incident cases of gout between 2006 and 2015 in western Sweden and 5 population controls per case matched for age, sex, and county were identified. Comorbidities were identified for 5 years preceding the index date. Follow-up ended at death, migration, or end of study on December 2017. Effect of gout on death risk was calculated using COX regression on the whole population and stratified by sex, adjusted for demographics, and comorbidities. Death incidence rates were compared between the two time periods, 2006-2010 and 2011-2015. Results: We identified 22,055 cases of incident gout and 98,946 controls, median age (Q1, Q3) 69-68 (57, 79/56, 78) years and 67.6-66.5% males. Except for dementia, all comorbidities were significantly more common at baseline among gout cases. Overall, the risk for death in incident gout was neither increased overall nor in men, but women had a 10% elevated risk. In adjusted models for cause-specific mortality, death from CVD, renal disease, and digestive system diseases were significantly increased in the total gout population while death from dementia, cancer, and lung diseases were significantly decreased. There were no significant differences in overall incident death rate ratios between cases and controls in the two time periods examined. Conclusions: An increased risk for CVD, renal disease, and diseases of the digestive system in patients with gout highlights the importance of addressing CVD risk factors in gout management. Gout was associated with reduced mortality from dementia, which may have implications on urate lowering therapy and possible effects on dementia risk.

Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration.

BACKGROUND: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. METHODS: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. RESULTS: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. CONCLUSION: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

The yield of a positive MRI of the spine as imaging criterion in the ASAS classification criteria for axial spondyloarthritis: results from the SPACE and DESIR cohorts.

OBJECTIVES: To assess the prevalence of spinal inflammation on MRI in patients with chronic back pain (CBP) of maximally 3 years duration and to evaluate the yield of adding a positive MRI-spine as imaging criterion to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). METHODS: Baseline imaging of the sacroiliac joints (X-SI), MRI of the sacroiliac joints (MRI-SI) and MRI-spine were scored by ≥2 experienced central readers per modality in the SPondyloArthritis Caught Early (SPACE) and DEvenir des Spondylarthropathies Indifférenciées Récentes (DESIR) cohorts. Inflammation suggestive of axSpA was assessed in the entire spine. A positive MRI-spine was defined by the presence of ≥5 inflammatory lesions. Alternative less strict definitions were also tested. RESULTS: In this study, 541 and 650 patients with CBP from the SPACE and DESIR cohorts were included. Sacroiliitis on X-SI and MRI-SI was found in 40/541 (7%) and 76/541 (14%) patients in SPACE, and in DESIR in 134/650 (21%) and 231/650 (36%) patients, respectively. In SPACE and DESIR, a positive MRI-spine was seen in 4/541 (1%) and 48/650 (7%) patients. Of the patients without sacroiliitis on imaging, 3/447 (1%) (SPACE) and 8/382 (2%) (DESIR) patients had a positive MRI-spine. Adding positive MRI-spine as imaging criterion led to new classification in only one patient in each cohort, as the other patients already fulfilled the clinical arm. Other definitions of a positive MRI-spine yielded similar results. CONCLUSION: In two cohorts of patients with CBP with a maximum symptom duration of 3 years, a positive MRI-spine was rare in patients without sacroiliitis on MRI-SI and X-SI. Addition of MRI-spine as imaging criterion to the ASAS axSpA criteria had a low yield of newly classified patients and is therefore not recommended.

Mortality in ankylosing spondylitis: results from a nationwide population-based study.

OBJECTIVES: Information on mortality in ankylosing spondylitis (AS) is scarce. Our study therefore aimed to assess: (1) mortality in AS versus the general population, and (2) predictors of death in the AS population. METHODS: Nationwide cohorts of patients with AS diagnosed at rheumatology or internal medicine outpatient clinics (n=8600) and age-matched, sex-matched and county-matched general population comparators (n=40 460) were identified from the National Patient Register and the census register, respectively. The follow-up period began on 1 January 2006 or at the first date of registered diagnosis thereafter and extended until death, emigration or 31 December 2012, whichever occurred first. Socioeconomic variables, AS-related clinical manifestations, joint surgery, comorbidities and medication were identified from other national registers. Cox regression models were used to determine mortality and predictors for death in the AS cohort. RESULTS: There were 496 deaths in the AS cohort and 1533 deaths in the control cohort resulting in an age-adjusted and sex-adjusted HR of 1.60 (95% CI 1.44 to 1.77), with increased mortality for men (age-adjusted HR=1.53, 95% CI 1.36 to 1.72) and women (age-adjusted HR=1.83, 95% CI 1.50 to 2.22). Within the AS cohort, statistically significant predictors for death were a lower level of education, general comorbidities (diabetes, infections, cardiovascular, pulmonary and malignant diseases) and previous hip replacement surgery. CONCLUSIONS: Mortality was increased for male and female patients with AS. Predictors of death within the AS cohort included socioeconomic status, general comorbidities and hip replacement surgery.

High serum cholesterol predicts rheumatoid arthritis in women, but not in men: a prospective study.

INTRODUCTION: Environmental exposures, including smoking, hormone-related factors, and metabolic factors, have been implicated in the etiology of rheumatoid arthritis (RA). A previous study has indicated that blood lipid levels may influence the development of RA. The objective of this study was to investigate the impact of serum total cholesterol and triglycerides on the risk of RA in a prospective study. METHODS: Among participants in a large population-based health survey (n = 33,346), individuals who subsequently developed RA were identified by linkage to four different registers and a structured review of the medical records. In a nested case-control study, with controls, matched for age, sex, and year of inclusion, from the health survey database, the relation between serum lipids (levels of total cholesterol and triglycerides) and future RA development was examined. RESULTS: In total, 290 individuals (151 men and 139 women) whose RA was diagnosed a median of 12 years (range of 1-28) after inclusion in the health survey were compared with 1160 controls. Women with a diagnosis of RA during the follow-up had higher total cholesterol levels at baseline compared with controls: odds ratio (OR) 1.54 per standard deviation; 95 % confidence interval (CI) 1.22-1.94. This association remained statistically significant in multivariate models adjusted for smoking and a history of early menopause and in analyses stratified by rheumatoid factor status and time to RA diagnosis. Total cholesterol had no significant impact on the risk of RA in men (OR 1.03; 95 % CI 0.83-1.26). Triglycerides did not predict RA in men or women. CONCLUSIONS: A high total cholesterol was a risk factor for RA in women but not in men. This suggests that sex-specific exposures modify the impact of lipids on the risk of RA. Hormone-related metabolic pathways may contribute to RA development.

How people with rheumatoid arthritis perceive leisure activities: a qualitative study.

OBJECTIVE: To explore how people with rheumatoid arthritis (RA) perceive leisure activities. METHOD: A phenomenographic approach using semi-structured interviews to explore the impact of RA on leisure pursuits was used. RESULTS: Three descriptive categories containing 11 conceptions emerged: (1) Experiencing constraints included four conceptions: seeing limitations, needing time, finding balance, being dependent. (2) Experiencing coherence included four conceptions: accepting feelings participating in a social context, being active, having insight. (3) Finding solutions included three conceptions: choosing, planning, and adapting. CONCLUSIONS: This study emphasizes the limited choices and problems people with RA had participating in leisure activities, as well as its impact on self-esteem.