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      Is Anti–Citrullinated Protein Antibody–Positive Rheumatoid Arthritis Still a More Severe Disease Than Anti–Citrullinated Protein Antibody–Negative Rheumatoid Arthritis? A Longitudinal Cohort Study in Rheumatoid Arthritis Patients Diagnosed From 2000 Onward

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          Abstract

          Objective

          Because of its association with joint destruction, anti–citrullinated protein antibody (ACPA)–positive rheumatoid arthritis (RA) is considered to be more severe than ACPA‐negative RA. Clinically relevant joint destruction is now infrequent thanks to adequate disease suppression. According to patients, important outcomes are pain, fatigue, and independence. We evaluated whether ACPA‐positive RA patients diagnosed during or after 2000 have more severe self‐reported limitations and impairments, including restrictions at work, than ACPA‐negative RA patients.

          Methods

          A total of 492 ACPA‐positive and 450 ACPA‐negative RA patients who fulfilled the 2010 criteria and were included in the Leiden Early Arthritis Clinic cohort during or after 2000 were compared for self‐reported pain, fatigue, disease activity, general well‐being (measured by numerical rating scales), physical function (measured by the Health Assessment Questionnaire), and work restrictions, including absenteeism at baseline and during the 4‐year followup. Linear mixed models were used.

          Results

          At disease presentation, ACPA‐negative patients had more severe pain, fatigue, self‐reported disease activity scores, and functional disability ( P < 0.05), although absolute differences were small. During followup, ACPA‐negative patients remained somewhat more fatigued ( P = 0.002), whereas other patient‐reported impairments and limitations were similar. Thirty‐eight percent of ACPA‐negative and 48% of ACPA‐positive patients reported absenteeism ( P = 0.30), with median 4 days missed in both groups in the last 3 months. Also, restrictions at work among employed patients and restrictions with household work were not statistically different at baseline and during followup.

          Conclusion

          In current rheumatology practice, ACPA‐positive RA is not more severe than ACPA‐negative RA in terms of patients’ relevant outcomes, including physical functioning and restrictions at work. This implies that efforts to further improve the disease course should be proportional to both disease subsets.

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          Most cited references40

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          The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.

          The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a "classification tree" schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91-94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
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            EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

            To formulate EULAR recommendations for the management of early arthritis. In accordance with EULAR's "standardised operating procedures", the task force pursued an evidence based approach and an approach based on expert opinion. A steering group comprised of 14 rheumatologists representing 10 European countries. The group defined the focus of the process, the target population, and formulated an operational definition of "management". Each participant was invited to propose issues of interest regarding the management of early arthritis or early rheumatoid arthritis. Fifteen issues for further research were selected by use of a modified Delphi technique. A systematic literature search was carried out. Evidence was categorised according to usual guidelines. A set of draft recommendations was proposed on the basis of the research questions and the results of the literature search.. The strength of the recommendations was based on the category of evidence and expert opinion. 15 research questions, covering the entire spectrum of "management of early arthritis", were formulated for further research; and 284 studies were identified and evaluated. Twelve recommendations for the management of early arthritis were selected and presented with short sentences. The selected statements included recognition of arthritis, referral, diagnosis, prognosis, classification, and treatment of early arthritis (information, education, non-pharmacological interventions, pharmacological treatments, and monitoring of the disease process). On the basis of expert opinion, 11 items were identified as being important for future research. 12 key recommendations for the management of early arthritis or early rheumatoid arthritis were developed, based on evidence in the literature and expert consensus.
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              Genetics and epigenetics of rheumatoid arthritis.

              Investigators have made key advances in rheumatoid arthritis (RA) genetics in the past 10 years. Although genetic studies have had limited influence on clinical practice and drug discovery, they are currently generating testable hypotheses to explain disease pathogenesis. Firstly, we review here the major advances in identifying RA genetic susceptibility markers both within and outside of the MHC. Understanding how genetic variants translate into pathogenic mechanisms and ultimately into phenotypes remains a mystery for most of the polymorphisms that confer susceptibility to RA, but functional data are emerging. Interplay between environmental and genetic factors is poorly understood and in need of further investigation. Secondly, we review current knowledge of the role of epigenetics in RA susceptibility. Differences in the epigenome could represent one of the ways in which environmental exposures translate into phenotypic outcomes. The best understood epigenetic phenomena include post-translational histone modifications and DNA methylation events, both of which have critical roles in gene regulation. Epigenetic studies in RA represent a new area of research with the potential to answer unsolved questions.
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                Author and article information

                Contributors
                a.c.boer@lumc.nl
                Journal
                Arthritis Care Res (Hoboken)
                Arthritis Care Res (Hoboken)
                10.1002/(ISSN)2151-4658
                ACR
                Arthritis Care & Research
                John Wiley and Sons Inc. (Hoboken )
                2151-464X
                2151-4658
                28 May 2018
                July 2018
                : 70
                : 7 ( doiID: 10.1002/acr.v70.7 )
                : 987-996
                Affiliations
                [ 1 ] Leiden University Medical Center Leiden The Netherlands
                [ 2 ] Care and Public Health Research Institute, and Maastricht University Medical Center Maastricht The Netherlands
                [ 3 ] Leiden University Medical Center, Leiden, and Erasmus Medical Center Rotterdam The Netherlands
                Author notes
                [*] [* ]Address correspondence to Aleid C. Boer, MD, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. E‐mail: a.c.boer@ 123456lumc.nl .
                Article
                ACR23497
                10.1002/acr.23497
                6033104
                29266813
                a69a57c5-6440-44df-b38a-e0deb1ebeec8
                © 2017 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 04 September 2017
                : 12 December 2017
                Page count
                Figures: 4, Tables: 2, Pages: 10, Words: 8166
                Funding
                Funded by: Netherlands Organization for Health Research and Development
                Funded by: European Research Council
                Funded by: European Union's Horizon 2020 Research and Innovation Programme
                Award ID: 714312
                Funded by: Dutch Arthritis Foundation
                Categories
                Original Article
                Rheumatoid Arthritis
                Custom metadata
                2.0
                acr23497
                July 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.3 mode:remove_FC converted:05.07.2018

                Rheumatology
                Rheumatology

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