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International audience; Aims: Biomarkers are not recommended until now to guide the management of patients with heart failure (HF). Soluble suppression of tumorigenicity 2 (sST2) appears as a promising biomarker. The current study considered pre-discharged sST2 values as a guide for medical management in patients admitted for acute HF decompensation, in an attempt to reduce hospital readmission.Methods and results: STADE-HF was a blinded prospective randomized controlled trial and included 123 patients admitted for acute HF. They were randomized into the usual treatment group (unknown sST2 level) or the interventional treatment group, for whom sST2 level was known and used on Day 4 of hospitalization to guide the treatment. The primary endpoint was the readmission rate for any cause at 1 month. It occurred in 10 patients (19%) in the usual group and 18 (32%) in the sST2 group without statistical difference (P = 0.11). Post hoc analysis in the whole group shows that the mean duration of hospitalization was lower in patients with low sST2 (

Objective: To explore the diagnostic contribution of the 18F-FDG-PET/CT in a population of patients with classical fever of unknown origin (FUO), to pinpoint its place in the diagnostic decision tree in a real-life setting, and to identify the factors associated with a diagnostic 18F-FDG-PET/CT. Method: All adult patients (aged ≥ 18 years) with a diagnosis of classical FUO who underwent an 18F-FDG-PET/CT in the University Hospital of Montpellier (France) between April 2012 and December 2017 were included. True positive 18F-FDG-PET/CT, which evidenced a specific disease causing FUO, were considered to be contributive. Results: Forty-four patients with FUO have been included (20 males, 24 females, mean age 57.5 ± 17.1 years). Diagnoses were obtained in 31 patients (70.5%), of whom 17 (38.6%) had non-infectious inflammatory diseases, 9 had infections (20.5%), and 3 had malignancies (6.8%). 18F-FDG-PET/CT was helpful for making a final diagnosis (true positive) in 43.6% of all patients. Sensitivity and specificity levels were 85% and 37%, respectively. A total of 135 investigations were performed before 18F-FDG-PET/CT, mostly CT scans (93.2%) and echocardiography (59.1%), and 108 after 18F-FDG-PET/CT, mostly biopsies (including the biopsy of a temporal artery) (25%) and MRIs (34%). In multivariate analysis, the hemoglobin level was significantly associated with a helpful 18F-FDG-PET/CT (p = 0.019, OR 0.41, 95% CI (0.20–0.87)), while the CRP level was not associated with a contributive 18F-FDG-PET/CT. Conclusion: 18F-FDG-PET/CT may be proposed as a routine initial non-invasive procedure in the diagnostic workup of FUO, especially in anemic patients who could be more likely to benefit from 18F-FDG-PET/CT.

We aimed to explore the relationship between comorbidities and the structural progression in symptomatic knee and/or hip osteoarthritis (OA) patients. We analyzed the 5-year outcome of non-obese participants (body mass index (BMI) &lt, 30 kg/m2) from the KHOALA cohort having symptomatic hip and/or knee OA (Kellgren and Lawrence (KL) ≥ 2). The primary endpoint was radiological progression, defined as ΔKL ≥ 1 of the target joint at 5 years. The secondary outcome was the incidence of total knee or hip replacement over 5 years. Dichotomous logistic regression models assessed the relationship of comorbidities with KL progression and joint replacement while controlling for gender, age and BMI. Data from 384 non-obese participants were analyzed, 151 with hip OA and 254 with knee OA. At 5 years, cardiovascular diseases (CVD) were significantly associated with the 5-year KL change in both knee (OR = 2.56 (1.14–5.78), p = 0.02) and hip OA (OR = 3.45 (1.06–11.17), p = 0.04). No significant relationship was found between any type of comorbidities and knee or hip arthroplasty. This 5-year association between CVD and radiological progression of knee and hip OA in non-obese participants argue for an integrated management of CVD in knee and hip OA non-obese patients.

Despite improvement in the prognosis of ANCA-associated vasculitides (AAVs), increased mortality, mainly from a cardiovascular origin, persists. We aimed to determine the role of cardiovascular risk factors (CVRFs) on the occurrence of major cardiovascular events (MACEs) in AAVs. Patients with AAVs were successively included in a prospective cohort study, which assessed CVRFs (defined by age &gt, 50 years in men and &gt, 60 years in women, personal history of cardiovascular disease, smoking status, obesity, diabetes, dyslipidemia, hypertension, and sedentary lifestyle), the use of glucocorticoids and immunosuppressive agents at baseline and during follow-up, and the occurrence of MACEs. One hundred and three patients were included, with a median follow-up time of 3.5 years. In the glucocorticoids and cyclophosphamide adjusted multivariate analysis, the occurrence of MACEs was associated with older age (p = 0.001, OR = 14.71, 95% CI (confidence interval) = 2.98–72.68), cardiovascular history (p = 0.007, OR (odds ratio) = 6.54, 95% CI = 1.66–25.71), sedentary lifestyle (p = 0.011, OR = 4.50, 95% CI = 1.42–14.29), hypertension (p = 0.017, OR = 5.04, 95% CI = 1.33–19.12), and dyslipidemia (p = 0.03, OR = 3.86, 95% CI = 1.14–13.09). The occurrence of MACEs was associated with the number of CVRFs (p &lt, 0.001), but not with the use of glucocorticoids or cyclophosphamide (p = 0.733 and p = 0.339, respectively). The implementation of a screening and management program for modifiable CVRFs, particularly hypertension, sedentary lifestyle, and dyslipidemia, may be beneficial for AAV patients in order to reduce their cardiovascular risk.

Background and objective Cardiovascular diseases (CVD) are the leading causes of death in chronic inflammatory rheumatic diseases and are not solely explained by the increased prevalence of cardiovascular (CV) risk factors in this population. Arterial stiffness, assessed primarily by pulse wave velocity (PWV) and more indirectly by augmentation index (AIx), is a surrogate marker of CVD that should be considered. The objective of this review was to investigate the relationship between arterial stiffness and chronic inflammatory and/or autoimmune diseases. Methods We performed a systemic literature review of articles published in Medline from January 2012 to April 2020 restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and rheumatoid arthritis, systemic lupus erythematosus, psoriasis, Sjogren's syndrome and ankylosing spondylitis. For each selected article, data on PWV and AIx were extracted and factors that may have an impact on arterial stiffness were identified. Results A total of 214 references were identified through database searching and 82 of them were retained for analysis. Arterial stiffness is increased in chronic inflammatory and autoimmune diseases. Traditional CV risk factors such as hypertension and dyslipidemia accentuate this relationship. Current data are insufficient to determine whether disease activity significantly influences arterial stiffness, whereas disease duration seems rather critical. TNF-alpha inhibitors and cardiorespiratory fitness tend to decrease arterial stiffness. Finally, increased arterial stiffness leads to diastolic dysfunction, which is the main mechanism of heart failure in chronic inflammatory rheumatic diseases. Conclusion CV risk assessment in chronic inflammatory and autoimmune diseases should also rely on PWV and AIx.

Primary Sjögren’s syndrome (pSS) is an autoimmune disease, associated with a high risk of lymphoma. Mounting evidence suggests that cardiovascular morbidity and mortality are higher in patients with pSS, although data are heterogeneous. The aim of this study was to assess whether pSS patients are at higher risk of hospitalisation for cardiovascular events (CVEs), venous thromboembolic events (VTEs), pulmonary hypertension (PH), and sleep apnoea syndrome (SAS). Through a nationwide population-based retrospective study using the French health insurance database, we selected new-onset pSS in-patients hospitalised between 2011 and 2018. We compared the incidence of CVEs (ischemic heart diseases (IHDs), strokes, and heart failure), SAS, VTEs, and PH with an age- and sex-matched (1:10) hospitalised control group. The calculations of adjusted hazard ratios (aHR) included available confounding factors. We studied 25,661 patients hospitalised for pSS compared with 252,543 matched patients. The incidence of hospitalisation for IHD, SAS, and PH was significantly higher in pSS patients (aHR: 1.20 (1.06–1.34), p = 0.003, aHR: 1.97 (1.70–2.28), p &lt, 0.001, and aHR: 3.32 (2.10–5.25), 0.001, respectively), whereas the incidence of stroke, heart failure, and VTE was the same between groups. Further prospective studies are needed to confirm these results and to explore the pathophysiological mechanisms involved.

Objectives To explore the 10-year tolerability profile of glucocorticoids (GC) use in patients with early RA. Methods Analysis of 10-year outcome from the early arthritis ESPOIR cohort. Patients were stratified in two groups, without or with GC treatment at least once during their follow-up. The primary outcome was a composite of deaths, cardiovascular diseases (CVD), severe infections and fractures. The weighted Cox time-dependent analysis model was used with inverse probability of treatment weighting (IPTW) propensity score method. Results Among the 608 patients [480 women, mean age of 47.5 (12.1) years], 397 (65%) received low-dose GC [median 1.9 mg/day (IQR 0.6–4.2), mean cumulative prednisone dose 8468 mg (8376), mean duration 44.6 months (40.1)]. In univariate analysis, over 95 total events (10 deaths, 18 CVDs, 32 fractures and 35 severe infections), patients taking GC experienced more events (n = 71) than those without GC (n = 24) (P =0.035). Highest cumulative exposure of GC (≥8.4 g) was associated with highest risk of occurrence of the primary outcome (24.3%, P =0.007), CVDs (7.9%, P =0.001) and severe infections (9.9%, P =0.024). The risk of events over time was significantly associated with GC, age, hypertension and ESR. The risk associated with GC treatment increased between the first follow-up visit [hazard ratio (HR) at 1 year = 0.46, 95% CI: 0.23, 0.90] and 10 years (HR = 6.83, 95% CI: 2.29, 20.35). Conclusion The 10-year analysis of this prospective early RA cohort supports a dose and time-dependent impact of low-dose GC treatment, with a long-term high risk of severe outcomes. Trial registration (ClinicalTrials.gov Identifier: NCT03666091).

International audience; We read with deep interest the report by Tepasse et al .1 concerning two cases of persisting viraemia in coronavirus disease 2019 (COVID‐19) with fatal outcome. Whilst severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) infection in the early stages of infection has been well described, less is known about the development of antibodies to SARS‐CoV‐2, clearance of RNA shedding and clinical outcome of COVID‐19. In addition, the impact of immunosuppressive treatments on disease severity is not yet established, but several reports suggest a more prolonged disease in patients under rituximab, a B‐cell depleting drug.2-4 Here we report a case of persisting COVID‐19, following combined treatment with rituximab and bendamustine for lymphoma, which immediately recovered after convalescent plasma transfusion. We think that this case raises promising perspectives for immunocompromised patients with persisting COVID‐19.

It has been well documented that patients with rheumatoid arthritis (RA) are at higher risk for many comorbidities1, even in early RA2. The concept of comorbidity refers to chronic conditions that coexist with the index disease, such as RA, with potential interactions between RA and comorbidities that may worsen patient global well-being. In fact, this concept does not seem so recent, because a global healthcare approach has always been the gold standard in the management of many chronic diseases. However, specifically regarding RA management, the innovative aspect lies in involving rheumatologists in addressing the field of comorbidities. Thanks to tight control of joint outcomes with targeted disease-modifying antirheumatic drugs (DMARD), the rheumatologists became involved in other dimensions of RA, such as quality of life or comorbidities. Evidenced-based and practical recommendations for screening and managing comorbidities in RA have been developed2,3,4,5,6. Such comorbidities in RA include various conditions such as cardiovascular diseases, hypertension (HTN), diabetes, pulmonary diseases, depression, osteoporosis, and malignancies. Comorbidities appear to be of utmost importance to consider, not only because of their high prevalence but also because of their potential involvement in RA outcome7. Comorbidities affect morbidity, increase mortality, impair quality of life, and affect response to treatment, while increasing the complexity of managing RA and its costs. This is also true in early RA. In the Canadian Early Arthritis cohort, comorbidities were associated with higher disease activity and worse functional status8. Indeed, comorbidities have been reported to be a negative predictor of achieving the treatment target, … Address correspondence to Dr. C. Roubille, Department of Internal Medicine, 371 Avenue du Doyen Gaston Giraud, CHU Montpellier, University of Montpellier, 34295 Montpellier, France. E-mail: c-roubille{at}chu-monpellier.fr

Background and objectives The optimization of immunosuppressive therapies has led to a marked improvement in the survival of ANCA-associated vasculitides (AAV). The main issue now appears to be the management of comorbidities and the improvement of quality of life. The objective of this review was to investigate the incidence and the impact of AAV-associated comorbidities, as well as the determinants of health-related quality of life (HRQoL). Methods We performed a systematic literature review of articles published in Medline from 2001 to 04/28/2020. We selected relevant articles about AAV-associated comorbidities as well as HRQoL and fatigue. For each selected article, data on the incidence of comorbidity were extracted, and factors associated with the Mental component score (MCS) and the Physical component score (PCS) were identified. Results Among the 10,993 references identified, 103 were retained for the final analysis. A significant increase in cardiovascular risk was evidenced, particularly for coronary artery disease and thromboembolic events, especially during the active phase of the disease. AAV was also associated with bronchiectasis, thyroid diseases and osteoporosis. A marked decrease in HRQoL and an increase in fatigue and anxiety were reported. Decrease in PCS and MCS was associated with fatigue, mood disorders, sleep disturbance, and/or unemployment. Conclusion The excess mortality of AAV is still a concern, partly in connection with cardiovascular and thromboembolic comorbidities. AAV patients also experiment a reduction in their HRQoL that requires integrated management. Patients with AAV need comorbidity management strategies to improve their quality of life and outcomes.

Background The long-term effect of comorbidities on progression of structural changes in osteoarthritis (OA) remains poorly understood. Patients with knee OA have been reported to be at increased risk of several comorbidities including cardiovascular diseases (CVD). Nevertheless, the impact of all comorbidities on structural progression and on arthroplasty, not only in knee but also in hip OA, should be further defined. Objectives The objective of our study was to explore the relationship between comorbidities and the progression of structural changes in symptomatic knee and/or hip OA patients over 5 years. Methods The KHOALA (Knee and Hip OsteoArthritis Long-term Assessment) cohort is a French prospective multicenter observational cohort that included 878 subjects, aged 40 to 75 years, with symptomatic hip and/or knee OA at baseline (Kellgren and Lawrence (KL) ≥2). The structural progression was defined by the increase of one point of KL (ΔKL ≥1) or incidence of total knee or hip replacement at 5 years. Various comorbidities were analyzed: cardiovascular diseases excluding hypertension (coronary artery disease, heart failure, stroke, lower limb arteriopathy), hypertension, diabetes, smoking, dyslipidemia, metabolic syndrome, osteoporosis, neurological (e.g. Parkinson’s disease, dementia), digestive (e.g. gastroesophageal reflux disease, ulcer), pulmonary (e.g. asthma, COPD), and psychiatric (depression, anxiety) diseases. Multivariate analysis was performed separately in hip and knee OA adjusted on age, sex and body mass index (BMI). Subjects with a BMI> 30 kg/m² were excluded from the analysis given the close relationship between obesity and the different comorbidities analyzed. Subjects with KL = 4 at the time of inclusion were also excluded from the analysis. Results Data from 631 non-obese subjects (BMI Conclusion This 5-year data analysis of the KHOALA cohort revealed a significant association between cardiovascular comorbidities and structural progression of knee OA in subjects without obesity (BMI Disclosure of Interests Camille Roubille Grant/research support from: expanscience, Joel Coste: None declared, Jeremie Sellam: None declared, Anne-Christine Rat: None declared, Francis Guillemin Grant/research support from: Expanscience, Christian Roux: None declared

International audience; Purpose of review: Hypertriglyceridemia occurs mainly because of metabolic disorders secondary to diabetes, alcohol intake, and/or overweight. Genetic factors have also been clearly identified in most severe cases. Triglycerides are generally considered as ‘bystanders’ for cardiovascular diseases. However, biological and basic research provides strong data suggesting that triglyceride-rich lipoproteins could be involved in the pathophysiology of cardiovascular diseases.Recent findings: The REDUCE-IT trial recently showed that icosapent ethyl reduces major cardiovascular events and related death.Summary: For many years, low-density lipoproteins (LDLs) have been considered the Holy Grail for atherosclerotic cardiovascular disease management. New data from basic research in biology, epidemiology, genetics, and preliminary clinical trials support the hypothesis that triglyceride-rich lipoproteins could be the causal factors for atherosclerotic cardiovascular disease; hence, triglyceride should be taken into consideration in the management of these patients. Omega-3-fatty acids used in the REDUCE-IT trial reduced the residual cardiovascular risk efficiently beyond statins. However, its effect has to be completely understood as it seems to be unrelated to LDLc or triglyceride reduction, but linked to pleiotropic effects involving inflammation, platelet adhesion, and plaque instability reduction, paving the way for trials that will target more specific potential pathophysiologic pathways.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been the cornerstone for the treatment of heart failure (HF) with reduced ejection fraction for decades. According to recent and promising studies, sacubitril/valsartan (SV) might be efficient in alternative indications in the area of HF with preserved left ventricular ejection fraction, chronic kidney disease, and so on. This review briefly summarizes these promising therapeutic options regarding SV and the potential limits and pitfalls for its use in routine practice (due to cognitive uncertainties).

Key points ASCVD reduction is based on LDL reduction, especially by statins. Highly elevated TG could be harmful, especially because of the risk of pancreatitis. Elevation of TG is mainly due to metabolic disorders and diabetes, alcohol intake and overweight. Genetic factors have been clearly identified in the most severe cases. TG have been generally considered as bystanders for cardiovascular diseases (CVD). Both biological and basic research provide strong data suggesting that TG-rich lipoproteins could be involved in the pathophysiology of CVD. Recent epidemiological and genetics studies strongly corroborate the causal role of TG in CVD. This paves the way for new approaches in the management of patients both for primary and secondary prevention.

International audience

Objective In the perspective of personalized management of osteoarthritis (OA), a clinically relevant concern is the impact of meniscal extrusion (Ext) on response to treatment. This study aimed at determining the effects of conventional OA pharmacological treatments and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes in the presence or absence of Ext, using data from the progression cohort of the Osteoarthritis Initiative. Methods In this longitudinal study, knee OA participants were stratified based on whether (+) or not (−) they received analgesics/NSAIDs (+ and −analgesics/NSAIDs) and/or Glu/CS (+ and −Glu/CS) for 24 consecutive months and on the presence (Ext+) or absence (Ext−) of medial meniscal extrusion at baseline. The main outcomes were knee structural changes including the loss of joint space width (JSW) and cartilage volume loss measured by quantitative MRI. Results In both − and +analgesics/NSAIDs groups ( n = 300 each), the Ext+ participants had more-advanced disease at baseline (T0) and more JSW loss and cartilage volume loss in the medial compartment ( p ≤ 0.003, univariate; p ≤ 0.049, multivariate analyses) at both 12 (T12) and 24 (T24) months compared to Ext− participants. In the −analgesics/NSAIDs group, Ext+ participants taking Glu/CS had significantly less cartilage volume loss in the medial plateau at T24 ( p ≤ 0.010, univariate and multivariate analyses). In the +analgesics/NSAIDs group at T24, Ext− participants taking Glu/CS had less cartilage volume loss in the global ( p ≤ 0.002, univariate and multivariate analyses) and medial and lateral plateaus ( p = 0.034 and p = 0.013, respectively, multivariate analysis). No significant difference in JSW loss was found between the groups. Conclusion This study is the first to demonstrate, using qMRI, that meniscal extrusion can modify the response to Glu/CS treatment in knee OA patients, depending on the severity of the disease.

Background: Smoking has been associated with psoriasis prevalence and severity. Objective: To evaluate prevalence of smoking in patients with psoriasis and to examine the relationship between smoking and psoriasis severity. Methods: MEDLINE, EMBASE, and Cochrane databases (1960-2012) and conference proceedings (2010-2012) were systematically searched using keywords relevant to psoriasis and smoking. Controlled studies addressing psoriasis and smoking status were included. A meta-analysis for the relative risk of smoking in psoriasis patients was performed. Results: Meta-analysis identified a significant association between smoking and psoriasis with a relative risk of 1.88 (95% CI, 1.66-2.13) for smoking in patients with psoriasis versus patients without psoriasis. Eight articles of 11 with data on smoking and psoriasis severity suggested that severity increases with smoking status. Conclusions: This literature review is in favor of a positive association between the prevalence of smoking and psoriasis as well as an association between smoking and severity of psoriasis.

Objective Studies have proposed vastus medialis (VM) muscle cross-sectional area change as a variable associated with cartilage volume loss in knee osteoarthritis (OA). However, the VM also includes fat (%Fat), which may influence knee function. This study analyzed the VM area and %Fat data, separately and in combination, to predict symptoms, cartilage volume loss, and bone marrow lesion (BML) change in knee OA. Methods This study included the according-to-protocol population (n = 143) of a 2-year knee OA randomized clinical trial having magnetic resonance imaging at baseline and 2 years. Correlations used multivariate analyses. Results Greater baseline value for VM area and %Fat were significantly associated with sex (male, area; female, %Fat), higher body mass index (BMI), and Western Ontario and McMaster Universities Osteoarthritis Index stiffness, function, and total scores (better, high area; worse, high %Fat). Moreover, a VM %Fat increase of 1% at 2 years was associated with worsening of cartilage volume loss in the global knee (P = 0.015) and some subregions (P ≤ 0.030), and with an increment of BML global score change (P < 0.001). A 1% decrease in VM area at 2 years was associated with worsening of knee pain score (P = 0.048). Importantly, the concurrent presence of low VM area, high VM %Fat, and high BMI identified a subgroup of patients with greater cartilage volume loss in the medial femur (P = 0.028) than the rest of the cohort. Conclusion These data demonstrated, for the first time, that VM fat content is a strong predictor of cartilage volume loss and the occurrence and progression of BML. Importantly, the combined data of VM area, VM %Fat, and BMI identified patients at higher risk for OA progression.

OBJECTIVE To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review. METHODS Electronic databases were systematically searched for randomized controlled trials. Studies were grouped based on disease, treatment, and site of BMD measurement. Change in BMD (ΔBMD) from baseline to end of study was recorded. Standardized mean difference (SMD) of ΔBMD between treatment and controls was standardized for meta-analyses and 95% confidence intervals (95% CIs) were calculated. RESULTS Treatment effects on BMD were not the primary outcomes of the trials. Thirteen studies were eligible (11 RA, 2 AS, 0 PsA, and 0 psoriasis). For RA, significantly less hand bone loss was seen with tumor necrosis factor inhibitors (TNFi; SMD ΔBMD 0.33 [95% CI 0.13, 0.53], P = 0.001, I(2) = 0%) and glucocorticoids (SMD ΔBMD 0.51 [95% CI 0.20, 0.81], P = 0.001, I(2) = 0%). TNFi had no significant effect on lumbar spine and hip BMD. Glucocorticoids were associated with a negative effect on lumbar spine (SMD ΔBMD -0.30 [95% CI -0.55, -0.04], P = 0.02, I(2) = 52%), but not hip BMD. For AS, a significant increase in BMD was seen with TNFi at the lumbar spine (SMD ΔBMD 0.96 [95% CI 0.64, 1.27], P

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p

ObjectiveTo explore the 7-year tolerability profile of glucocorticoids (GC) for early rheumatoid arthritis (RA).MethodsWe examined data for 602 patients with RA from the early arthritis Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort (ResultsAmong the 602 patients with RA (476 women (79%), mean age 48±12 years), 386 with GC (64.1%) received low-dose prednisone (mean 3.1±2.9 mg/day for the entire follow-up): 263 started GC during the first 6 months (68%), and the mean duration of total GC treatment was 1057±876 days. As compared with patients without GC (216 (35.9%)), those with GC showed greater use of non-steroidal anti-inflammatory drugs, synthetic and biological disease-modifying antirheumatic drugs and had more active disease disability, higher C reactive protein and anticitrullinated protein antibody levels. Among 65 events (7 deaths, 14 cardiovascular diseases, 19 severe infections and 25 fractures), 44 and 21 occurred in patients with and without GC (p=0.520). Infections were more frequent, although not significantly, in patients with than without GC (p=0.09). On weighted Cox proportional-hazards analysis, with use of propensity score and inverse-probability-of-treatment weighting, and including age, gender, history of hypertension and GC treatment, outcomes did not differ with and without GC (p=0.520; HR=0.889; 95% CI 0.620 to 1.273).ConclusionsThis 7-year analysis of the ESPOIR cohort supports the good safety profile of very low-dose GC for early active RA.

To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of conventional osteoarthritis (OA) pharmacological treatment and those of the combination of glucosamine and chondroitin sulfate (Glu/CS) on knee structural changes.Six hundred patients with knee OA were stratified based on whether or not they received for 24 consecutive months the OA conventional pharmacological treatment and/or Glu/CS. The main outcomes were knee structural changes, including the loss of joint space width (JSW) and of cartilage volume measured by quantitative MRI.Participants reported taking (+) (n=300) or not taking (-) (n=300) OA treatment (analgesic/NSAIDs). The +analgesic/NSAIDs participants had higher Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores (p0.001) and smaller JSW (p=0.01), reflecting more severe disease at baseline. In the -analgesic/NSAIDs group, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial central plateau (p=0.007). Further subdivision revealed that this effect of Glu/CS occurred in participants with a higher severity of the disease (JSW≤median). In the +analgesic/NSAIDs group, those taking Glu/CS had significantly reduced loss of cartilage volume in the global plateau at 12 months (p=0.05), and in the central plateau at 24 months (p=0.05). These effects occurred in participants with less disease severity (JSWmedian). By contrast, no significant reduction in JSW was found between all groups.In +analgesic/NSAIDs groups and -analgesic/NSAIDs groups, participants who took Glu/CS had reduced loss of cartilage volume over 24 months in subregions when assessed with qMRI, arguing for a disease-modifying effect of Glu/CS which could not be identified by X-rays.

Anti-inflammatory drugs consist of non-steroidal anti-inflammatory drugs (NSAIDs) including non-selective nsNSAIDs, aspirin, and cyclooxygenase-2 (COX-2)-selective inhibitors also referred to as coxibs, and glucocorticoids (GCs). They are worldwide prescribed drugs for many musculoskeletal conditions, such as osteoarthritis and inflammatory rheumatic diseases. Anti-inflammatory drugs can exert deleterious effects on the cardiovascular system, excluding aspirin. NSAIDs, especially coxibs, have been demonstrated to increase cardiovascular risk and have generated many concerns leading to the reassessment of their benefit/risk ratio. GCs may also induce cardiovascular events, but evidence seems to be less clear. Before prescribing these drugs, an assessment of cardiovascular risk may be judicious. In this review, anti-inflammatory drugs, coxibs, nsNSAIDs and GCs, and the risk of cardiovascular events will be discussed.

Purpose and medical hypothesis: Rest is usually recommended in acute pericarditis, as it could help to lower heart rate (HR) and contribute to limit ‘‘mechanical inflammation’’. Whether HR on admission could be correlated and perhaps participate to inflammation has not been reported. Methods: Between March 2007 and February 2010, we conducted a retrospective study on all patients admitted to our center for acute pericarditis. Diagnosis criteria included two of the following ones: typical chest pain, friction rub, pericardial effusion on cardiac echography, or typical electrocardiogram (ECG) findings. Primary endpoint was biology: CRP on admission, on days 1, 2, 3, and especially peak. Results: We included 73 patients. Median age was 38 years (interquartiles 28–51) and median hospitalization duration was 2.0 days (1.5–3.0). Median heart rate was 88.0 beats per minute (bpm) on admission (interquartiles 76.0–100.0) and 72.0 on discharge (65.0–80.0). Heart rate on admission was significantly correlated with CRP peak (p < 0.001), independently of temperature on admission, hospitalization duration and age. Recurrences occurred within 1 month in 32% of patients. Heart rate on hospital discharge was correlated with recurrence, independently of age. Conclusion: In acute pericarditis, heart rate on admission is independently correlated with CRP levels and heart rate on discharge seems to be independently correlated to recurrence. This could suggest a link between heart rate and pericardial inflammation.

Objective: To determine whether serum levels of a proliferation-inducing ligand (APRIL) are altered in patients with systemic lupus erythematosus (SLE), and correlate with disease parameters. Methods: Clinical and biological parameters were analysed for 43 patients that fulfilled American College of Rheumatology (ACR) criteria for SLE classification and were positive for anti-double-stranded DNA (dsDNA) antibodies at least once in their medical records. Tests included measurement of serum levels of the tumour necrosis factor (TNF) family members APRIL and B lymphocyte stimulator (BLyS; a cytokine shown to promote SLE disease). Results: Median APRIL levels were elevated in patients with SLE compared to patients with osteoarthritis and healthy controls, but did not correlate with the SLE Disease Activity Index (SLEDAI). APRIL serum levels showed an inverse correlation with BLyS serum levels (r = −0.339; p = 0.03). For patients with SLE with positive anti-dsDNA titres (>40 arbitrary units (AU)/ml) at inclusion (n = 25), circulating APRIL was inversely correlated with BLyS levels (r = −0.465; p = 0.022) and anti-dsDNA antibody titres (r = −0.411; p = 0.046). In a follow-up study at their second visit, 27 patients showed an inverse correlation of APRIL serum levels with BLyS (r = −0.398; p = 0.03) as well as with anti-dsDNA (r = −0.408; p = 0.03) titres and SLEDAI (r = −0.408; p = 0.01). Conclusion: The inverse correlation observed between APRIL and BLyS suggests that APRIL acts as a protective factor. APRIL and BLyS may thus have opposite roles in SLE, which must be considered when defining therapeutic applications of these cytokines.

Resume Introduction Les pericardites aigues representent une cause frequente d’hospitalisation en cardiologie. Cette enquete prospective avait plusieurs buts : une description de la population, et du bilan initial a visee etiologique, l’evaluation de l’interet de la prise en charge combinee entre internistes et cardiologues. Patients et methodes Entre mai 2005 et septembre 2007, tous les patients presentant une pericardite aigue, sont enregistres de facon prospective et tricentrique. Les donnees de l’interrogatoire et de l’examen clinique sont completees par un ECG, une echocardiographie, des examens biologiques standardises. Deux consultations sont prevues a un mois (cardiologue et interniste). Resultats Cent trois patients etaient enregistres, d’un âge moyen de 43 ans. La presentation etait classique dans la majorite des cas (cliniquement dans 60 % des cas et 59 % concernant l’ECG). Au plan biologique, la troponine etait elevee dans 30 % des cas, alors que la CRP etait normale au moment du diagnostic dans 27 % des cas, s’elevait de facon significative entre l’admission et le premier jour ( p = 0,002). Une cause probable etait retrouvee chez 44 patients. Pour 26 patients (soit 24,3 %), un diagnostic etiologique precis etait etabli : six cancers de voisinage, une hemopathie maligne, trois connectivites, une seroconversion EBV, une seroconversion parvovirus B19, deux patients VIH en rupture therapeutique, quatre maladies inflammatoires, trois atteintes endocriniennes, une œsophagite, un sepsis d’origine dentaire, une amylose, une pancreatite, un refus de dialyse. Dix-huit diagnostics (soit 16,5 % des patients) ont ete poses de novo, dont au moins 12 beneficiaient d’une prise en charge specifique. Conclusions La population des patients presentant une pericardite est tres heterogene. La prise en charge combinee entre cardiologues et internistes permet de systematiser la prise en charge et le bilan etiologique initial, afin d’augmenter le depistage precoce de pathologies pouvant beneficier d’un traitement specifique. Notre enquete se poursuit par le suivi des patients au long cours, avec pour objectif le diagnostic d’autres etiologies non revelees initialement et pour en connaitre l’evolution.

Objective.Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO.Methods.Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960–12/2012), together with abstracts from major rheumatology and dermatology congresses (2010–2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels.Results.A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%.Conclusion.These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.

We wish to address the comments by Felson1 regarding our recently published article . 2 This study used the osteoarthritis initiative (OAI) cohort database, which offers a unique opportunity to explore the onset and progression of knee osteoarthritis (OA) and the potential effects of treatments on the natural progression of the disease. Obviously, as does any observational study, such cohort has limitations. The rationale behind the referenced work was to build a study design that circumvented some of the limitations of the OAI cohort by selecting a subpopulation of the participants. We wanted to study, as reliably as possible, the potential disease-modifying osteoarthritis drug (DMOAD) effects of glucosamine (Glu) and chondroitin sulfate (CS) in a design that would mimic a randomised controlled trial (RCT) with all of the restrictions that such a study design could impose in the context of an observational study. From the first-line analysis it was obvious that the patient population was heterogeneous from a clinical standpoint, with one of the main factors being related to disease treatment (±analgesics/non-steroidal anti-inflammatory drugs (NSAIDs)) and the implicit severity of the disease based on symptoms and joint space width (JSW). This observation was interesting and, importantly, clinically relevant. As outlined in the study design section, we …

Atherosclerosis remains the predominant cause of cardiovascular diseases (CVDs) and heart failure, which are the leading causes of death worldwide. It is now well established that patients with rheumatoid arthritis (RA) experience an accelerated atherosclerosis increasing their risk of CVD and related mortality compared with the general population [Nicola et al. 2005; Roubille and Tardif, 2013; Solomon et al. 2003]: a recent meta-analysis highlighted an increased risk of all CVDs of 48% in RA, as well as of myocardial infarction of 68% and of strokes of 41% [Avina-Zubieta et al. 2012]. Over the past decade, inflammation appeared to be the cornerstone of both atherosclerosis and RA. Indeed, atherosclerosis is no longer considered a condition in which lipids are being deposited passively in the arterial wall but rather fully recognized as an inflammatory, dynamic and complex disease involving multiple cell types, including inflammatory cells as well as endothelial and smooth muscle cells [Newby, 2010; Roubille et al. 2013c; Shah, 2009]. RA has long been recognized as a systemic inflammatory syndrome with several extra-articular manifestations such as interstitial lung disease and vasculitis. However, these features do not occur in all RA patients. In contrast, vascular inflammation and accelerated atherosclerosis may affect a larger RA population, probably all RA patients, especially in the early stage of the disease, as pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 as well as B cells contribute to the pathogenesis of both atherosclerosis and RA [Hansson, 2005]. Moreover, traditional cardiovascular risk factors should not be overlooked. Hence, assessment and management of cardiovascular risk factors is recommended for RA patients [Haraoui et al. 2012; Peters et al. 2010]. The treatment goal should be to achieve remission or at least low disease activity as early as possible [Smolen et al. 2010], not only to lead to better structural and functional outcomes, but also to reduce the cardiovascular risk [Peters et al. 2010].

To the Editor: We thank Castaneda, et al 1 for their comments on our article2. We do support comorbidity management in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and psoriasis (PsO) in daily practice to ensure optimal care and outcomes, and completely agree with the recently published Spanish recommendations3. Given that patients with RA have increased risk of cardiovascular (CV) morbidity and mortality4, CV monitoring appears critical. In the CARMA (CARdiovascular in rheuMAtology) study, Castaneda, et al 5 reported that patients with RA, PsA, and PsO had higher prevalence of CV events while receiving biological therapy despite being in low disease activity for almost half of the patients. Notably, almost half of the patients also received nonsteroidal antiinflammatory drugs and/or glucocorticoids (patients with RA), which may have increased CV risk6. Regardless of the other confounding factors, these data reinforce the importance of CV monitoring and … Address correspondence to Dr. C. Roubille, University of Montreal Hospital Research Center (CRCHUM), Notre-Dame Hospital, Montreal, Quebec H2L 1S6, Canada. E-mail: camille.roubille{at}gmail.com

Although often considered as "begnin", acute infections in young healthy adults can lead to heart inflammation, including acute myocarditis. We report a rare case of myopericarditis in a young immunocompetent adult, in the context of recent toxoplasmosis infection. Clinical presentation was common acute pericarditis, but with risk biomarkers: high troponin I levels and multiple inflammation-compatible images on MR-scan. Diagnosis of myopericarditis was established. In spite of spontaneous favourable clinical evolution, troponin remained elevated. MR-scan is shown; acute myocarditis in the context of an acute toxoplasmosis infection is discussed. Cardiol Res. 2012;3(4):189-191 doi: https://doi.org/10.4021/cr200w

Osteoarthritis (OA) management is currently based on a wide spectrum of therapeutic options to relieve pain, but other OA drugs with disease-modifying properties (DMOADs) are being developed. There are presently agents that are symptomatic slow-acting drugs for OA (SYSADOA), which not only reduce joint pain but could also slow the structural disease progression in the joint. Targeting cartilage changes (catabolism and anabolism), subchondral bone remodeling, and synovial inflammation are the three main thrusts of research in DMOAD development. Promising emerging therapies include platelet-rich plasma (PRP), bone remodeling modulators, and inflammatory inhibitors. OA should be considered a dynamic process and may be a systemic disease with several tissues and pathways to target for DMOAD development. With the advent of DMOADs, physicians should aim at treating the “patient” rather than the “disease.” Combining therapeutics at both local and systemic levels to impact both symptoms and joint structural changes will likely be the future strategy instead of a sole drug, at least at the beginning of the treatment. Selectively targeting some phenotypes of OA patients evidenced by sensitive tools, such as magnetic resonance imaging (MRI), may allow the development of DMOADs based on personalized medicine.

Introduction Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP). Methods This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed. Results Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P

Introduction To evaluate the impact of meniscal extrusion (Ext) on knee osteoarthritis (OA) structural progression and on response to strontium ranelate (SrRan) treatment at 36 months in patients with (+) or without (-) Ext, in association (+) or not (-) with bone marrow lesions (BML) in the medial compartment using X-rays (JSW) and qMRI. Methods Patients from the qMRI substudy of the SEKOIA trial (SrRan 1 g/day, n = 113; SrRan 2 g/day, n = 105; placebo, n = 112) were stratified based on whether meniscal extrusion and/or BML were present or not in the medial compartment. Results In the placebo group, Ext+ patients (n = 26) had more JSW loss (p = 0.002) and cartilage volume loss in the global knee (p = 0.034) and plateau (p = 0.005), and medial compartment (p = 0.0005) than Ext- patients (n = 86). Ext-BML+ patients (n = 18) demonstrated more JSW loss (p = 0.003) and cartilage volume loss in the global (p = 0.020) and medial femur (p = 0.055) than Ext-BML- (n = 68). Compared to Ext+ BML- (n = 14), Ext+ BML+ patients (n = 12) had more cartilage volume loss in the global femur (p = 0.028), with no change in JSW. The JSW loss (p = 0.0004) and cartilage volume loss (global knee, p = 0.033, medial compartment, p = 0.0005) were greater when Ext and BML were simultaneously present in the medial compartment. SrRan 2 g/day treatment demonstrated a reduction in OA knee structural progression with qMRI, but not with JSW, in which less cartilage volume loss was found in the plateaus (p = 0.007) in Ext+ patients (n = 15), and in the medial plateau (p = 0.046) in patients in whom both Ext and BML were co-localized. Conclusion The findings of this study are novel and could have an impact on future strategies regarding clinical trials. Indeed, data first argue for a combined, cumulative effect of meniscal extrusion and bone marrow lesions on cartilage loss and, secondly, they showed that SrRan may have protective effects in OA patients with meniscal extrusion as well as when both meniscal extrusion and BML are co-localized.

Background Twenty to fifty percent of patients with psoriasis have depressive symptoms. Objective To describe the effects of biologics (tumour necrosis factor inhibitors [TNFi] or interleukin 12/23 inhibitors [IL-12/23i]) on depressive symptoms in patients with psoriasis. Methods Electronic databases were searched for randomized controlled trials (RCTs) examining the effects of biologics on depressive symptoms in adults with psoriasis. Results Of the 305 publications identified, three RCTs were included in a systematic review. In a trial evaluating ustekinumab, mean change in Hospital and Anxiety Depression Rating Scale at 24 weeks from baseline was 3.1 with ustekinumab (P

Comment in "A common progenitor cell in LCH and ECD. [Blood. 2014]"; International audience; Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy-proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotypes of these patients with those of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43 years. ECD followed (n = 12) or was diagnosed simultaneously with (n = 11) but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon alpha-2a treatment in only 50% of patients (8 of 16). We found the BRAF(V600E) mutation in 11 (69%) of 16 LCH lesions and in 9 (82%) of 11 ECD lesions. Eight patients had mutations in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.

Acute viral infections can lead to heart inflammation, including acute myocarditis. We report a rare case of myopericarditis in a young immunocompetent adult, in a context of recent Cytomegalovirus (CMV) infection. The clinical presentation was an influenzae-like syndrome, classical for a CMV infection, without any chest pain or dyspnea, but a systematic exploration showed multiple inflammation-compatible myopericardial images on MNR-scan. The diagnosis of asymptomatic myopericarditis was established. We present the MNR-scan findings and discuss the CMV cardiac effects and systematic cardiac MRI interest in viral infection.

Objective To explore, using MRI, the disease-modifying effect of strontium ranelate (SrRan) treatment on cartilage volume loss (CVL) and bone marrow lesions (BMLs) in a subset of patients from a Phase III clinical trial in knee osteoarthritis (OA) (SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA)). Material and methods Patients with primary symptomatic knee OA were randomised to receive either SrRan 1 g/day or 2 g/day or placebo (SEKOIA study). A subset of these patients had MRIs at baseline, 12, 24 and 36 months to assess the knee cartilage volume and BMLs. Missing values were imputed and the analyses were adjusted according to Bonferroni. Results In this MRI subset, the distribution of patients (modified intention-to-treat; n=330) was 113, 105 and 112 for SrRan 1 g/day, 2 g/day and placebo, respectively. The groups were fairly balanced at baseline regarding demographics, clinical symptoms or imaging characteristics. Treatment with SrRan 2 g/day significantly decreased CVL on the plateaus at 12 (p=0.002) and 36 (p=0.003) months compared with placebo. Of note, in the medial femur and plateau, SrRan 1 g/day, but not SrRan 2 g/day, had more CVL than placebo. In patients with BML in the medial compartment at baseline, the BML score at 36 months was decreased in both treatment groups compared with the placebo group (SrRan 1 g/day, p=0.002 and SrRan 2 g/day p=0.001, respectively), and CVL significantly decreased with SrRan 2 g/day (p=0.023) in the plateau compared with placebo. Conclusions In knee OA patients, treatment with SrRan 2 g/day was found to have beneficial effects on structural changes by significantly reducing CVL in the plateau and BML progression in the medial compartment.

Osteoarthritis (OA) is a dynamic process involving the main tissues of the joint for which a global approach should be considered. No disease-modifying OA drug (DMOAD) has yet been approved. New therapeutic strategies are needed that would be cost effective by reducing the need for pharmacological interventions and surgical management while targeting specific pathways leading to OA. The treatment landscape of OA is about to change based on new agents having shown some structural effects and emerging therapies with DMOAD effects.In this review based on a Medline (via PubMed) search, promising new and emerging therapies with a potential structural effect (DMOAD) will be discussed including growth factors, platelet-rich plasma, autologous stem cells, bone remodeling modulators, cytokine inhibition, gene therapy, and RNA interference.DMOAD development should focus on targeting some phenotypes of OA patients evidenced with sensitive techniques such as magnetic resonance imaging, as a single treatment will unlikely be appropriate for all OA patients. This will allow the development of DMOADs based on personalized medicine. An exciting new era in DMOAD development is within reach, provided future clinical trials are sufficiently powered, systematically designed, use the appropriate evaluation tools, and target the appropriate categories of OA patients.

Objective: To review published cases of induced or exacerbated interstitial lung disease (ILD) in rheumatoid arthritis (RA) associated with non-biologic disease-modifying antirheumatic drugs (nbDMARDs) and biologics and to discuss clinical implications in daily practice. Methods: We performed a systematic literature review from 1975 to July 2013 using Medline, Embase, Cochrane, and abstracts from the ACR 2010–2012 and EULAR 2010–2013 annual meetings. Case reports and series that suggest a causative role of nbDMARDs (methotrexate [MTX], leflunomide [LEF], gold, azathioprine [AZA], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) and biologic agents (TNF inhibitors [TNFi], rituximab [RTX], tocilizumab [TCZ], abatacept [ABA], and anakinra) in causing ILD or worsening a pre-existing ILD in RA patients were included. Results from observational and postmarketing studies as well as reviews on this topic were excluded from the qualitative analysis but still considered to discuss the implication of such drugs in generating or worsening ILD in RA patients. Comparisons were made between MTX-induced ILD in RA and the cases reported with other agents, in terms of clinical presentation, radiological features, and therapeutic management and outcomes. Results: The literature search identified 32 articles for MTX, 12 for LEF (resulting in 34 case reports), 3 for gold,1 for AZA, 4 for SSZ, 27 for TNFi (resulting in 31 case reports), 3 for RTX, 5 for TCZ (resulting in 8 case reports), and 1 for ABA. No case was found for HCQ or anakinra. Common points are noted between LEFand TNFi-related ILD in RA: ILD is a rare severe adverse event, mostly occurs within the first 20 weeks after initiation of therapy, causes dyspnea mostly in older patients, and can be fatal. Although no definitive causative relationship can be drawn from case reports and observational studies, these data argue for a pulmonary follow-up in RA patients with pre-existing ILD, while receiving biologic therapy or nbDMARDs. Conclusion: As previously described for MTX, growing evidence highlights that LEF, TNFi, RTX, and TCZ may induce pneumonitis or worsen RA-related pre-existing ILD. Nonetheless, identifying a causal relationship between RA therapy and ILD-induced toxicity clearly appears difficult, partly because it is a rare condition.

Rest is usually recommended in acute pericarditis and acute myocarditis. Given that myocarditis often leads to hospitalization, this task seems easy to carry out in hospital practice; however, it could be a real challenge at home in daily life. Heart rate-lowering treatments (mainly beta-blockers) are usually recommended in case of acute myocarditis, especially in case of heart failure or arrhythmias, but level of proof remains weak. Calcium channel inhibitors and digoxin are sometimes proposed, albeit in limited situations. It is possible that rest or even heart rate-lowering treatments could help to manage these patients by preventing heart failure as well as by limiting "mechanical inflammation" and controlling arrhythmias, especially life-threatening ones. Whether heart rate has an effect on inflammation remains unclear. Several questions remain unsolved, such as the duration of such treatments, especially in light of new heart rate-lowering treatments, such as ivabradine. In this review, we discuss rest and heart-rate lowering medications for the treatment of pericarditis and myocarditis. We also highlight some work in experimental models that indicates the beneficial effects of such treatments for these conditions. Finally, we suggest certain experimental avenues, through the use of animal models and clinical studies, which could lead to improved management of these patients.

Patients with chronic inflammatory diseases such as rheumatoid arthritis have a higher risk of cardiovascular diseases and related mortality compared to the general population. This risk is first due to classical cardiovascular risk factors but also due to systemic inflammation which is independently involved, causing accelerated atherosclerosis, myocardial infarction, cerebrovascular disease and heart failure (HF). Pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 could be major actors on this pathophysiology. Biologics are effective specific treatments in the management of inflammatory rheumatic and systemic diseases. In this review, beneficial and deleterious effects on the heart and vessels of the biologics used in the management of inflammatory arthritis and vasculitides will be discussed, focusing on TNF-alpha, IL-6 and IL-1 blockades, and anti-CD20. Noninflammatory cardiac conditions, such as heart failure, myocardial infarction, and cardiovascular conditions such as atherosclerosis, as well as inflammatory diseases including vasculitides will be discussed.

Background Some adipokines have been associated with osteoarthritis (OA) incidence and potentially its progression. Only a few studies have looked at their association with, and prediction of, structural progression of knee OA using quantitative MRI. Objectives This study contrasted serum levels of 5 adipokines to the changes in cartilage volume and examined if they could predict the occurrence of a total knee replacement (TKR). Methods This post hoc analysis was performed on the ATP population (n=138) of a knee OA randomized clinical trial 1,2. The serum levels of the obesity factors Adipsin/Complement Factor D (CFD), Leptin (LEP), Adiponectin (ADIPOQ), Resistin (RETN), and Serpin E1 (SERPINE1) as well as the cartilage volume were determined at baseline and at 24 month follow-up. TKR incidence of the study knee up to 4 years post trial completion was also evaluated. Univariate and multivariate analyses controlling for age, gender, BMI, and treatment allocation were performed. Results Higher baseline BMI was associated with greater baseline CFD and LEP levels (p≤0.006) and lower baseline ADIPOQ levels (p Conclusions These data demonstrate that both CFD and LEP predict greater cartilage volume loss over time in the lateral femur and medial compartment, respectively. Baseline “at risk” levels of LEP, CFD and ADIPOQ are associated with a greater occurrence of TKR. These findings add further insight to the role of adipokines in knee OA structural progression and outcome. References Raynauld JP et al. Ann Rheum Dis. 2009;68:938-47. Raynauld JP et al. Ann Rheum Dis. 2011;70:1382-8. Acknowledgements *Equal participation in the study Disclosure of Interest None declared

We thank Dr Boers for the interesting comments1 on our paper2. First, the decision to exclude studies reporting less than 400 patients was made after noticing that most of these studies had less than 1 year of follow-up or had large drop-outs with few remaining patients at or beyond 1 year. We also reviewed the abstract by Tarp et al .3 Among a total of 4831 subjects, 1944 were specifically analysed for …

Background Knee osteoarthritis (OA) structural changes are complex and comprise cartilage volume loss as well as meniscal lesions, which were shown to promote cartilage loss. Recently, strontium ranelate (SrRan) was demonstrated to have DMOAD properties (1,2) . Objectives We thus further evaluated the role of meniscal extrusion (mExt) on knee OA progression and its impact on response to SrRan treatment assessed by X-rays (change in joint space width [JSW]) and qMRI (cartilage volume loss [CVL] in the medial compartment) at 36 months (M36) in subjects with (mExt+) or without (mExt) meniscal extrusion, in association (+) or not (-) with bone marrow lesions (BML). Methods Patients from the qMRI substudy of the SrRan Efficacy in Knee OsteoarthrItis triAl (SEKOIA) (modified intention-to-treat, n=330) were stratified based on whether mExt (mExt+, n=60; mExt-, n=270) and BML were present or not (BML+, n=84; BML-, n=246) and on their association in the medial compartment at baseline. CVL was assessed by qMRI and JSW by X-rays at baseline and M36. Results In the placebo group, mExt+ patients demonstrated significantly more JSW loss (-0.76±0.67 mm; p=0.002) and CVL in the medial compartment (-10.40±4.23%; p=0.0005) than mExt- patients (-0.35±0.61 mm and -7.60±4.63%, respectively). mExt-/BML+ patients (n=18) had significantly more JSW loss (-0.77±0.68 mm; p=0.003) and a trend (-9.57±5.29%; p=0.090) toward more CVL compared to mExt-/BML- patients (n=68) (-0.23±0.55 mm and -7.08±4.33%, respectively). mExt+/BML+ patients (n=12) had a trend toward more CVL in the medial compartment (-11.22±1.90%; p=0.103) than mExt+/BML- (n=14) (-9.69±5.50%), while JSW change showed no difference. Importantly, the JSW loss and CVL in the medial compartment were greater when mExt and BML were both present simultaneously in this compartment. In mExt+ patients, while no difference was found in the JSW loss between groups, SrRan at 2 g/day reduced the CVL in the plateaus (-5.74±3.54%; p=0.007) and a trend toward a decrease in the medial plateaus (-4.90±5.19%; p=0.081) compared to the placebo (-10.01±5.79% and -9.07±8.74% respectively). In the mExt+/BML+ patients, SrRan 2 g/day significantly reduced the CVL in the medial plateaus (-1.13±2.24% vs -11.45±4.47% for the placebo; p=0.046), whereas there was no difference for the JSW loss. Conclusions The progression of knee OA assessed both by X-rays and qMRI was greater in mExt+ patients, and was further increased when co-localized with BML. Based on qMRI, SrRan 2 g/day showed beneficial DMOAD structural effects in mExt+ and mExt+/BML+ patients, targeting a subpopulation at higher risk of knee OA progression, while JSW loss was not sensitive enough to provide evidence of such effects. References Reginster JY. et al. Ann Rheum Dis 2013;72:179-86. Pelletier JP et al. Ann Rheum Dis. 2013 Dec 2. doi: 10.1136/annrheumdis-2013-203989. Disclosure of Interest C. Roubille: None declared, J. Martel-Pelletier Shareholder of: ArthroLab Inc., F. Abram Employee of: ArthroLab Inc., M. Dorais Consultant for: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J.-P. Pelletier Shareholder of: ArthroLab Inc. DOI 10.1136/annrheumdis-2014-eular.2539

Background The Osteoarthritis Initiative (OAI) is the largest knee osteoarthritis (OA) observational cohort. It provides the possibility to study the evolution of OA structural changes over time and the associated risk factors. It also allows the potential disease-modifying OA drug (DMOAD) effects to be explored in patients over time. Objectives To determine, using data from participants enrolled in the progression cohort of the OAI, the effects of existing meniscal extrusion on the extent of cartilage loss and structural changes over time, and response to pharmacological treatment including the combination of glucosamine and chondroitin sulfate (Glu/CS). Methods Knee OA patients were stratified based on the presence/absence of medial meniscal extrusion at baseline and on whether or not they received conventional OA pharmacological treatment (analgesics/non-steroidal anti-inflammatory drugs [NSAIDs]) and/or Glu/CS for 24 consecutive months. The main outcomes were knee structural changes including the cartilage volume measured by quantitative magnetic resonance imaging (MRI) and of loss of joint space width (JSW). Results Participants reported taking (+) (n=300) or not taking (−) (n=300) OA treatment (analgesics/NSAIDs). The participants with meniscal extrusion had more severe disease at baseline. In the −analgesics/NSAIDs group with meniscal extrusion, participants taking Glu/CS had significantly reduced loss of cartilage volume at 24 months in the medial tibiofemoral compartment (p=0.02) and lateral plateau (p=0.05). No effect of Glu/CS was observed in patients without extrusion. In the +analgesic/NSAIDs group without meniscal extrusion, those taking Glu/CS had significantly reduced loss of cartilage volume in the global knee (p=0.055), medial compartment (p=0.05), lateral plateau (p=0.007), and trochlea (p=0.04). No effect of Glu/CS treatment occurred in participants with extrusion. No significant reduction in JSW was found between those taking (+) and not taking (−) Glu/CS treatment. Conclusions This study confirms that combined administration of Glu/CS has significant protective effects on structure in knee OA. The presence of meniscal extrusion was found to be an important factor that can influence the drug effect on cartilage volume. X-rays were found to be much less sensitive than MRI at documenting the protective effect of treatment on structural changes. Disclosure of Interest : J.-P. Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica, C. Roubille: None declared, F. Abram Employee of: ArthroLab Inc., P. Delorme: None declared, J.-P. Raynauld Consultant for: ArthroLab Inc., J. Martel-Pelletier Shareholder of: ArthroLab Inc., Consultant for: Bioiberica DOI 10.1136/annrheumdis-2014-eular.2248

Background Cardiovascular events (CVE) are increased in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (PsO) patients. Objectives To determine the impact on CVE from methotrexate (MTX), TNF inhibitors (TNFi), corticosteroids (CS) and non-steroidal anti-inflammatory drugs (NSAIDs) (non-selective [ns-]NSAIDs and coxibs) in RA, PsA, and PsO. Methods Medline, Embase, Cochrane databases were systematically searched. Observational studies and randomized trials reporting CVE (myocardial infarction [MI], heart failure [HF], strokes, and major cardiovascular adverse effects [MACEs]) in RA and in PsA/PsO patients treated with MTX, TNFi, CS and NSAIDs were considered. Studies with mean age of 80 years were excluded. Random-effects meta-analyses were performed. Results Out of 2630 references, 34 studies were included, 28 for RA and 6 for PsA/PsO. In RA, both TNFi (RR 0.70, 95% CI, 0.54-0.90; p=0.005) and MTX (RR 0.72, 95% CI, 0.57-0.91; p=0.007) decreased all CVE. TNFi decrease MI, strokes and MACEs. MTX decreases MI. NSAIDs increased all CVE (RR 1.18, 95% CI 1.01-1.38; p=0.04) and strokes. Among NSAIDs only rofecoxib (RR 1.58, 95% CI 1.24-2.00; p Conclusions In RA, TNFi and MTX are associated with a decrease in all CVE while CS are associated with an increase of all CVE. The deleterious effect of NSAIDs on CVE is related to rofecoxib. While current evidence suggests deleterious cardiovascular effects of CS and rofecoxib in RA, targeting inflammation with MTX and TNFi may be cardioprotective. Disclosure of Interest C. Roubille Grant/research support: This study was supported by an unrestricted grant from AbbVie. Fellowship grants/bursary from the Foundation of the University of Montreal Hospital Center (CHUM)., V. Richer Grant/research support: This study was supported by an unrestricted grant from AbbVie., T. Starnino Grant/research support: This study was supported by an unrestricted grant from AbbVie., C. McCourt Grant/research support: This study was supported by an unrestricted grant from AbbVie. Salary for the fellowship in Vancouver was funded by a Fellowship from Janssen-Ortho Canada and the British Association of Dermatology., A. McFarlane Grant/research support: This study was supported by an unrestricted grant from AbbVie., P. Fleming Grant/research support: This study was supported by an unrestricted grant from AbbVie., S. Siu Grant/research support: This study was supported by an unrestricted grant from AbbVie., J. Kraft Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support from Abbvie, Amgen, Galderma, Janssen, Novartis., Consultant for: Abbvie, Amgen, Galderma, Janssen, Novartis, Leo Speakers bureau: Abbvie, Amgen, Galderma, Janssen, Leo., C. Lynde Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma., Consultant for: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma., Speakers bureau: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma, J. Pope Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support from AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium., Consultant for: AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium., S. Keeling Grant/research support: This study was supported by an unrestricted grant from AbbVie. Unrestricted educational funding received from the following:Pfizer, Janssen, Astrazeneca, Roche., Consultant for: Participated in advisory boards as consultant for:Janssen, AbbVie, Roche, Amgen., W. Gulliver Grant/research support: study was supported by an unrestricted grant from AbbVie. Research support from Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant., Consultant for: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant., Speakers bureau: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant, J. Dutz Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support Abbvie, Centocor, Janssen- Ortho, Novartis, ONO Pharmaceuticals, Roche., Consultant for: Janssen-Ortho, AbbVie Amgen, Leo, Roche Speakers bureau: Janssen-Ortho, AbbVie Amgen, Leo., L. Bessette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research support AbbVie, UCB, Janssen, and Amgen. Consultant for: AbbVie, UCB, Janssen, and Amgen., Speakers bureau: AbbVie, UCB, Janssen, and Amgen., R. Bissonnette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Research grants and honoraria AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute., Consultant for: AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute., B. Haraoui Grant/research support: This study was supported by an unrestricted grant from AbbVie. Grant support from Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB., Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB. DOI 10.1136/annrheumdis-2014-eular.5448

Background Inflammatory arthritis is a risk factor for osteoporosis and it may be that treating systemic inflammation can improve bone mineral density (BMD). Objectives The aim of this study was to examine if DMARDs, steroids, and biologic therapies for rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PSO), and ankylosing spondylitis (AS) affect BMD. The aim of this study was to examine if DMARDs, steroids, and biologics for rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis (PSO), and ankylosing spondylitis (AS) affect BMD. Methods Medline, Embase, and Cochrane were searched from 1960 to present using English randomised controlled trials in adults. Review articles were excluded. Studies were grouped based on disease, treatment type, and site of BMD measurement (wrist, lumbar spine (LS), hip). ΔBMD were reported as standardized mean difference. Results 393 studies were identified; 13 were eligible (11 RA, 0 PsA, 0 PSO, 2 AS). For RA, significantly less wrist bone loss was seen with biologics (ΔBMD =0.27SD, 95% CI 0.07-0.47, P=0.009, I 2 =0%) and corticosteroids (ΔBMD =0.54SD, 95% CI 0.23-0.85, P=0 2 =0%). Biologics had no significant effect on LS and hip BMD. Corticosteroids had more bone loss compared to placebo on LS (ΔBMD = -0.25SD, 95% CI -0.42 to -0.08, P=0.003, I 2 =52%) but no difference for hip. For AS, significant BMD increase was seen with biologics in both LS (ΔBMD = 0.98SD, 95% CI 0.73-1.23, P 2 =16%) and hip (ΔBMD = 0.38SD, 95% CI 0.14-0.63, P=0.002, I 2 =0%). PsA and PSO could not be analyzed due to no suitable RCTs. Conclusions Based on our RA analysis, biologics and steroids were associated with less wrist bone loss (where synovitis is often present) but had no effect on BMD at the hip. Corticosteroids were associated with more bone loss in LS whereas biologics had no effect on BMD at the LS. For AS, biologics were associated with increase in both LS and hip BMD. Disclosure of Interest S. Siu Grant/research support: This study was supported by an unrestricted grant from AbbVie. B. Haraoui Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other grant support from Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB. Consultant for: Abbvie, Amgen, BMS, Celgene, Janssen, Pfizer, Roche, UCB. C. Roubille Grant/research support: This study was supported by an unrestricted grant from AbbVie. Fellowship grants/bursary from the Foundation of the University of Montreal Hospital Center (CHUM). V. Richer Grant/research support: This study was supported by an unrestricted grant from AbbVie. T. Starnino Grant/research support: This study was supported by an unrestricted grant from AbbVie. C. McCourt Grant/research support: This study was supported by an unrestricted grant from AbbVie. Salary for the fellowship in Vancouver was funded by a Fellowship from Janssen-Ortho Canada and the British Association of Dermatology. A. McFarlane Grant/research support: This study was supported by an unrestricted grant from AbbVie. P. Fleming Grant/research support: This study was supported by an unrestricted grant from AbbVie. J. Kraft Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support from Abbvie, Amgen, Galderma, Janssen, Novartis. Consultant for: Abbvie, Amgen, Galderma, Janssen, Novartis, Leo. Speakers bureau: Abbvie, Amgen, Galderma, Janssen, Leo. C. Lynde Grant/research support: This study was supported by an unrestricted grant from AbbVie. Investigator support: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. Consultant for: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. Speakers bureau: Abbvie, Amgen, Celgene, Janssen-Ortho, Novartis, Eli Lilly, Merck, Leo Pharma. W. Gulliver Grant/research support: This study was supported by an unrestricted grant from AbbVie. Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. Consultant for: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. Speakers bureau: Abbott/AbbVie, Actelion, Amgen, Astellas, Bio-K, Celgene, Galderma, Janssen, LEO Pharma, Merck/Schering, Novartis, Pfizer, Roche and Valeant. S. Keeling Grant/research support: This study was supported by an unrestricted grant from AbbVie. Unrestricted educational funding received from the following:Pfizer, Janssen, Astrazeneca, Roche; Participated in advisory boards as consultant for:Janssen, AbbVie, Roche, Amgen. J. Dutz Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other research support Abbvie, Centocor, Janssen- Ortho, Novartis, ONO Pharmaceuticals, Roche. Consultant for: Janssen–Ortho, AbbVie Amgen, Leo, Roche. Speakers bureau: Janssen-Ortho, AbbVie Amgen, Leo. L. Bessette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Other research support AbbVie, UCB, Janssen, and Amgen. Consultant for: AbbVie, UCB, Janssen, and Amgen. Speakers bureau: AbbVie, UCB, Janssen, and Amgen. R. Bissonnette Grant/research support: This study was supported by an unrestricted grant from AbbVie. Resdearch grnats and honoraria AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute. Consultant for: AbbVie, Amgen, Celgene, Eli-Lilly Galderma, Incyte, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Tribute. J. Pope Grant/research support: This study was supported by an unrestricted grant from AbbVie. AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium, Consultant for: AbbVie, Actelion, Amgen, Astra Zeneca, Bayer, BMS, Celgene, Genentech, GSK, BMS, Jansen & Jansen, MedImmune, Mediquest, Novartis, Pfizer, Roche, United Chemicals Belgium DOI 10.1136/annrheumdis-2014-eular.2540