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      The association between increased body mass index and response to conventional synthetic disease-modifying anti-rheumatic drug treatment in rheumatoid arthritis: results from the METEOR database

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          Abstract

          Background

          Few data exist on the association between increased BMI and response to conventional synthetic DMARDs (csDMARDs) in RA. We aimed to explore the association between increased (overweight or obese) BMI on csDMARD prescribing, MTX dose and disease activity over 12 months.

          Methods

          Participants in an international RA database were stratified into early (<1 year post-diagnosis) and established RA. EULAR response, 28-joint DAS (DAS28) remission and treatments were recorded at baseline, 6 months and 12 months. Increased BMI was explored in early and established RA as predictors of good EULAR response, DAS28 remission, number of csDMARDs and MTX dose, using logistic and linear regression.

          Results

          Data from 1313 patients, 44.3% with early RA, were examined. In early RA, increased BMI was not significantly associated with remission. In established RA, obese patients on monotherapy were significantly less likely to achieve good EULAR response or DAS28 remission at 6 months and more likely to be treated with combination csDMARDs compared with normal BMI. In patients taking MTX, overweight and obese patients with early and established RA were exposed to higher MTX doses (mono- and combination therapy), with a mean dose of 20 mg/week, compared with 15 mg/week in those of normal BMI.

          Conclusion

          We observed that compared with patients with normal BMI, overweight and obese individuals experienced more intensive csDMARD exposures. Similar response rates were observed in early RA but increased BMI was associated with reduced response in established RA. Optimization of targeted RA treatment remains important, particularly in those with increased BMI where response in established disease may be attenuated.

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          Most cited references38

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          Obesity in autoimmune diseases: not a passive bystander.

          In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases.
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            Development and validation of the european league against rheumatism response criteria for rheumatoid arthritis: Comparison with the preliminary american college of rheumatology and the world health organization/international league against rheumatism criteria

            To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WHO)/International League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA).
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              Overweight decreases the chance of achieving good response and low disease activity in early rheumatoid arthritis.

              To investigate whether overweight/obesity at diagnosis affects the chances of decrease in disease activity and pain in early rheumatoid arthritis (RA). We investigated incident RA cases from the population-based Epidemiological Investigation of risk factors for Rheumatoid Arthritis (EIRA) study (2006-2009, N=495) with clinical follow-up in the Swedish Rheumatology Quality Register. At diagnosis, 93% received disease-modifying antirheumatic drugs (DMARDs) (86% methotrexate). The odds of achieving a good response according to the DAS28-based European League Against Rheumatism (EULAR) criteria, low disease activity (DAS28<3.2), remission (DAS28<2.6) or pain remission (visual analogue scale ≤20 mm) at 3-months and 6-months follow-up, were calculated using logistic regression, adjusting for potential confounders. Significant dose-response relationships were found between Body Mass Index (BMI) and change of disease activity as well as pain at both time points. Patients with BMI ≥25 had 51% lower odds of achieving low disease activity (odds ratio (OR=0.49 (95% CI 0.31 to 0.78)) and 42% lower odds of remission (OR=0.58 (95% CI 0.37 to 0.92)) at the 6-months visit, compared to normal-weight patients. This effect was also present at 3 months, where we also found a 43% decreased odds of pain remission (OR=0.57 (95% CI 0.37 to 0.88)). No effect modification was found for anti-citrullinated protein antibody (CCP)-status, sex, prednisolone treatment or DAS28 at diagnosis. Overweight at diagnosis significantly decreases the chance of achieving good disease control during the early phase of RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Rheumatology
                Oxford University Press (OUP)
                1462-0324
                1462-0332
                February 01 2022
                February 02 2022
                April 30 2021
                February 01 2022
                February 02 2022
                April 30 2021
                : 61
                : 2
                : 713-722
                Affiliations
                [1 ]Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool
                [2 ]Department of Rheumatology, Aintree University Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool
                [3 ]Faculty of Health, Social Care and Medicine, Edge Hill University, Ormskirk, UK
                [4 ]Department of Rheumatology, Leiden University Medical Center, Leiden
                [5 ]Amsterdam Rheumatology Center, Academic Medical Center, Amsterdam
                [6 ]Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
                Article
                10.1093/rheumatology/keab389
                33930113
                19955c6a-7333-4d07-ad23-8b50940d33cb
                © 2021

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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