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      Comorbidities in Spondyloarthritis

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          Abstract

          Comorbidities in spondyloarthritis (SpA) add to the burden of disease by contributing to disease activity, functional and work disability, and mortality. Thus, awareness of comorbidities in SpA is crucial to improve their screening and management and to ultimately improve outcomes in those affected. Osteoporosis has been reported to be the most prevalent comorbidity in SpA, and its risk is increased in these patients, compared with the general population; the risk of vertebral fractures requires further evaluation. Cardiovascular risk is also increased in this population, both due to an increase of the traditional cardiovascular risk factors in these patients, but also due to the presence of inflammation. The role of non-steroidal anti-inflammatory drugs in this increased risk needs further elucidation, but there is consensus on the need to encourage smoking cessation and to perform periodic evaluation of cardiovascular risk in these patients, particularly in the case of change in treatment course. Concerning the risk of cancer, no increased risk inherent to SpA seems to exist. However, an increased neoplastic risk can occur due to SpA treatments, e.g., P-UVA. Data are sparse on the risk of infections compared with rheumatoid arthritis, but there appears to be no risk in the absence of TNF-inhibitor exposure. Regardless of which comorbidity, a gap exists between recommendations for their management and actual implementation in clinical practice, suggesting that there is still a need for improvement in this area. Systematic screening for these comorbidities should improve both short- and long-term outcomes in SpA patients.

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          The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

          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<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.
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            Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn's disease

            Background As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited. Objective To analyse the long-term safety of adalimumab treatment. Methods This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data. Results The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population. Conclusions Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.
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              Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease.

              Glucocorticoids have adverse systemic effects, including obesity, hypertension, and hyperglycemia, that may predispose to cardiovascular disease. The effect of glucocorticoid use on cardiovascular disease has not been quantified. To test the hypothesis that users of exogenous glucocorticoids have an increased risk for cardiovascular disease. A cohort study using a record linkage database. Tayside, Scotland, United Kingdom. 68,781 glucocorticoid users and 82,202 nonusers without previous hospitalization for cardiovascular disease who were studied between 1993 and 1996. The average daily dose of glucocorticoid exposure during follow-up was categorized as low (inhaled, nasal, and topical only), medium (oral, rectal, or parenteral or =7.5 mg of prednisolone equivalent). Poisson regression model, sensitivity analysis, and propensity score methods were used to investigate the association between glucocorticoid exposure and cardiovascular outcome. 4383 cardiovascular events occurred in 257,487 person-years of follow-up for a rate of 17.0 (95% CI, 16.5 to 17.5) per 1000 person-years in the comparator group, and 5068 events occurred in 212,287 person-years for a rate of 23.9 (CI, 23.2 to 24.5) per 1000 person-years in the group exposed to glucocorticoids (22.1, 27.2, and 76.5 in low, medium, and high groups, respectively). The absolute risk difference was 6.9 (CI, 6.0 to 7.7) per 1000 person-years (5.1, 10.1, and 59.4, respectively). After adjustment for known covariates, the relative risk for a cardiovascular event in patients receiving high-dose glucocorticoids was 2.56 (CI, 2.18 to 2.99). Because the data were observational, residual confounding cannot be excluded. Treatment with high-dose glucocorticoids seemed to be associated with increased risk for cardiovascular disease.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                12 March 2018
                2018
                : 5
                : 62
                Affiliations
                [1] 1Rheumatology B Department, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris , Paris, France
                [2] 2INSERM (U1153) PRES Sorbonne Paris-Cité , Paris, France
                [3] 3Academic Rheumatology Department, King’s College London , London, United Kingdom
                [4] 4Department of Rheumatology, Whittington Hospital , London, United Kingdom
                Author notes

                Edited by: Ying Ying Leung, National University of Singapore, Singapore

                Reviewed by: Praveena Chiowchanwisawakit, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand; Fawad Aslam, Mayo Clinic Arizona, United States

                *Correspondence: Anna Moltó, anna.molto@ 123456cch.aphp.fr

                Specialty section: This article was submitted to Rheumatology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2018.00062
                5857562
                29594122
                057935c8-37b0-43a3-8d14-1a4e2ef089ff
                Copyright © 2018 Moltó and Nikiphorou.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 December 2017
                : 20 February 2018
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 123, Pages: 10, Words: 9837
                Categories
                Medicine
                Review

                spondyloarthritis,comorbidity,cardiovascular,osteoporosis,infection,cancer

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