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      Pretreatment multi-biomarker disease activity score and radiographic progression in early RA: results from the SWEFOT trial

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          Abstract

          Objectives

          Prediction of radiographic progression (RP) in early rheumatoid arthritis (eRA) would be very useful for optimal choice among available therapies. We evaluated a multi-biomarker disease activity (MBDA) score, based on 12 serum biomarkers as a baseline predictor for 1-year RP in eRA.

          Methods

          Baseline disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), disease activity score based on C-reactive protein (DAS28-CRP), CRP, MBDA scores and DAS28-ESR at 3 months were analysed for 235 patients with eRA from the Swedish Farmacotherapy (SWEFOT) clinical trial. RP was defined as an increase in the Van der Heijde-modified Sharp score by more than five points over 1 year. Associations between baseline disease activity measures, the MBDA score, and 1-year RP were evaluated using univariate and multivariate logistic regression, adjusted for potential confounders.

          Results

          Among 235 patients with eRA, 5 had low and 29 moderate MBDA scores at baseline. None of the former and only one of the latter group (3.4%) had RP during 1 year, while the proportion of patients with RP among those with high MBDA score was 20.9% (p=0.021). Among patients with low/moderate CRP, moderate DAS28-CRP or moderate DAS28-ESR at baseline, progression occurred in 14%, 15%, 14% and 15%, respectively. MBDA score was an independent predictor of RP as a continuous (OR=1.05, 95% CI 1.02 to 1.08) and dichotomised variable (high versus low/moderate, OR=3.86, 95% CI 1.04 to 14.26).

          Conclusions

          In patients with eRA, the MBDA score at baseline was a strong independent predictor of 1-year RP. These results suggest that when choosing initial treatment in eRA the MBDA test may be clinically useful to identify a subgroup of patients at low risk of RP.

          Trial registration number

          WHO database at the Karolinska Institute: CT20080004; and clinicaltrials.gov: NCT00764725.

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          Most cited references31

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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). EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity. EULAR response criteria had good construct, criterion, and discriminant validity, ACR and WHO/ILAR criteria showed only good criterion validity. EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA.
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            How to read radiographs according to the Sharp/van der Heijde method.

            This article is a short overview of the development of the Sharp/van der Heijde methods for scoring radiographs of hands and feet in rheumatoid arthritis, in addition to a detailed description on how to use the scoring method.
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              Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold values.

              To estimate the disease activity score (DAS)28-C-reactive protein (CRP) threshold values that correspond to DAS28-erythrocyte sedimentation rate (ESR) values for remission, low disease activity and high disease activity in patients with rheumatoid arthritis. DAS28 data were analysed using a large observational study (Institute of Rheumatology Rheumatoid Arthritis) database of 6729 patients with rheumatoid arthritis. Firstly, the relationship between the DAS28-ESR and the DAS28-CRP values was analysed. Secondly, the best DAS28-CRP trade-off values for each threshold were calculated using receiver operating characteristic (ROC) curves. The correlation coefficient of ESR versus CRP was 0.686, whereas that of DAS28-ESR versus DAS28-CRP was 0.946, showing the strong linear relationship between DAS28-ESR and DAS28-CRP values. DAS28-CRP threshold values corresponding to remission, low disease activity and high disease activity were 2.3, 2.7 and 4.1, respectively. The sensitivity and specificity from the ROC curves were gradually reduced as DAS28 values became lower. This study showed that DAS28-CRP and DAS28-ESR were well correlated, but the threshold values should be reconsidered. As the results were derived from only Japanese patients, it is essential to compare DAS28-CRP threshold values in people of other ethnic groups.
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                Author and article information

                Journal
                Ann Rheum Dis
                Ann. Rheum. Dis
                annrheumdis
                ard
                Annals of the Rheumatic Diseases
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                0003-4967
                1468-2060
                June 2015
                8 May 2014
                : 74
                : 6
                : 1102-1109
                Affiliations
                [1 ]Unit of Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institute , Stockholm, Sweden
                [2 ]Crescendo Bioscience Inc. , South San Francisco, California, USA
                [3 ]Rheumatology Unit, Department of Medicine, Karolinska University Hospital and Karolinska Institute , Stockholm, Sweden
                [4 ]Scott Cruickshank and Associates Inc. , Santa Barbara, California, USA
                [5 ]Section of Rheumatology, Institution of Clinical Sciences, University Hospital , Lund, Sweden
                [6 ]Section of Rheumatology, Department of Medicine,Helsingborg Hospital , Helsingborg, Sweden
                [7 ]Department of Orthopaedics, Institution of Clinical Sciences, Lund University , Lund, Sweden
                Author notes

                Handling editor Tore K Kvien

                [Correspondence to ] Karen Hambardzumyan, Department of Medicine, Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Karolinska Institute, D1:00 Karolinska University Hospital, Solna, Stockholm 17176, Sweden; karen.hambardzumyan@ 123456ki.se
                Article
                annrheumdis-2013-204986
                10.1136/annrheumdis-2013-204986
                4431327
                24812287
                3308515f-3271-40f0-953a-049b5aaad2f6
                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

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

                History
                : 27 November 2013
                : 4 April 2014
                : 13 April 2014
                Categories
                1506
                Clinical and Epidemiological Research
                Extended report
                Custom metadata
                unlocked

                Immunology
                rheumatoid arthritis,disease activity,anti-tnf,cytokines,patient perspective
                Immunology
                rheumatoid arthritis, disease activity, anti-tnf, cytokines, patient perspective

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