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      Predicting unfavorable long-term outcome in juvenile idiopathic arthritis: results from the Nordic cohort study

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          Abstract

          Background

          The aim was to develop prediction rules that may guide early treatment decisions based on baseline clinical predictors of long-term unfavorable outcome in juvenile idiopathic arthritis (JIA).

          Methods

          In the Nordic JIA cohort, we assessed baseline disease characteristics as predictors of the following outcomes 8 years after disease onset. Non-achievement of remission off medication according to the preliminary Wallace criteria, functional disability assessed by Childhood Health Assessment Questionnaire (CHAQ) and Physical Summary Score (PhS) of the Child Health Questionnaire, and articular damage assessed by the Juvenile Arthritis Damage Index-Articular (JADI-A). Multivariable models were constructed, and cross-validations were performed by repeated partitioning of the cohort into training sets for developing prediction models and validation sets to test predictive ability.

          Results

          The total cohort constituted 423 children. Remission status was available in 410 children: 244 (59.5%) of these did not achieve remission off medication at the final study visit. Functional disability was present in 111/340 (32.7%) children assessed by CHAQ and 40/199 (20.1%) by PhS, and joint damage was found in 29/216 (13.4%). Model performance was acceptable for making predictions of long-term outcome. In validation sets, the area under the curves (AUCs) in the receiver operating characteristic (ROC) curves were 0.78 (IQR 0.72–0.82) for non-achievement of remission off medication, 0.73 (IQR 0.67–0.76) for functional disability assessed by CHAQ, 0.74 (IQR 0.65–0.80) for functional disability assessed by PhS, and 0.73 (IQR 0.63–0.76) for joint damage using JADI-A.

          Conclusion

          The feasibility of making long-term predictions of JIA outcome based on early clinical assessment is demonstrated. The prediction models have acceptable precision and require only readily available baseline variables. Further testing in other cohorts is warranted.

          Electronic supplementary material

          The online version of this article (10.1186/s13075-018-1571-6) contains supplementary material, which is available to authorized users.

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          Most cited references23

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          2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features.

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            Preliminary criteria for clinical remission for select categories of juvenile idiopathic arthritis.

            To develop preliminary criteria for inactive disease and clinical remission for select categories of juvenile idiopathic arthritis (JIA), and to decide what such clinical states should predict in terms of probability of disease recurrence. A Delphi serial questionnaire consensus-formation approach was used initially to gather criteria in use by pediatric rheumatologists (PR) for defining clinical remission in oligoarticular (persistent and extended), rheumatoid factor (RF) positive and negative polyarticular, and systemic JIA. Results from sequential questionnaires provided an agenda for a nominal group technique (NGT) conference to reach consensus on unresolved questions. One hundred and thirty PR from 34 countries responded to the questionnaires and 20 PR from 9 countries attended the conference. Draft criteria for inactive disease include the following: no active arthritis; no fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA; no active uveitis; normal erythrocyte sedimentation rate or C-reactive protein; and a physician's global assessment of disease activity rated at the best score possible for the instrument used. According to consensus vote, 6 continuous months of inactive disease on medication defines clinical remission on medication, while 12 months of inactive disease off all anti-arthritis (and anti-uveitis) medications defines clinical remission off medication. The finalized criteria for remission off medication ideally should predict that a patient has
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              Seeking insights into the EPidemiology, treatment and Outcome of Childhood Arthritis through a multinational collaborative effort: Introduction of the EPOCA study

              The epidemiology of juvenile idiopathic arthritis (JIA) is variable worldwide. In particular, a wide disparity exists in the prevalence of the diverse disease subtypes across different geographic areas. The therapeutic approach to JIA is not standardized and no established and widely accepted guidelines are available. In the past decade, there have been important progresses in the management of the disease, but the availability of the novel and costly biologic medications is not uniform throughout the world. This issue may have significant impact on disease prognosis, with children living in poorer countries being at greater risk of accumulating disease- and treatment-related damage than children followed in Western pediatric rheumatology centers. The multinational study of the EPidemiology, treatment and Outcome of Childhood Arthritis (EPOCA study) is aimed to obtain information on the frequency of JIA subtypes in different geographic areas, the therapeutic approaches adopted by pediatric rheumatologists practicing in diverse countries or continents, and the disease and health status of children with JIA currently followed worldwide. Parent- and child-reported outcomes are meant to be recorded through the administration of a new multidimensional questionnaire, the Juvenile Arthritis Multidimensional Assessment Report (JAMAR). The first step of the study is based on the translation and cross-cultural adaptation of the questionnaire in the national language of each participating country. Each center is, then, asked to enroll a sample of consecutive JIA patients, who should undergo a retrospective assessment and a cross-sectional evaluation, including completion of the JAMAR, a standardized joint examination, and the assessment of articular and extra-articular damage. At the end of May 2012, 124 centers in 55 countries have agreed to participate in the study. The JAMAR has been or is currently being translated in 38 national languages. The target patient sample is more than 10,000 JIA children worldwide.
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                Author and article information

                Contributors
                +4792466162 , veronika.rypdal@unn.no
                ellen.d.arnstad@ntnu.no
                kristiina.alto@hus.fi
                lillemor.berntson@telia.com
                maria.ekelund@rjl.se
                anders.fasth@pediat.gu.se
                miagleru@rm.dk
                troeherl@rm.dk
                susan.nielsen@regionh.dk
                suvi.peltoniemi@hus.fi
                zak@dadlnet.dk
                marite.rygg@ntnu.no
                martin.rypdal@uit.no
                ellen.berit.nordal@unn.no
                Journal
                Arthritis Res Ther
                Arthritis Res. Ther
                Arthritis Research & Therapy
                BioMed Central (London )
                1478-6354
                1478-6362
                3 May 2018
                3 May 2018
                2018
                : 20
                : 91
                Affiliations
                [1 ]ISNI 0000 0004 4689 5540, GRID grid.412244.5, Department of Pediatrics, University Hospital of North Norway, ; Tromsø, Norway
                [2 ]ISNI 0000000122595234, GRID grid.10919.30, Department of Clinical Medicine, , UIT the Arctic University of Norway, ; Tromsø, Norway
                [3 ]ISNI 0000 0001 1516 2393, GRID grid.5947.f, Department of Clinical and Molecular Medicine, , NTNU - Norwegian University of Science and Technology, ; Trondheim, Norway
                [4 ]ISNI 0000 0004 0627 3093, GRID grid.414625.0, Department of Pediatrics, , Levanger Hospital, Nord-Trøndelag Hospital Trust, ; Levanger, Norway
                [5 ]ISNI 0000 0004 0410 2071, GRID grid.7737.4, Hospital for Children and Adolescents, , University of Helsinki, ; Helsinki, Finland
                [6 ]ISNI 0000 0004 1936 9457, GRID grid.8993.b, Department of Women’s and Children’s Health, , Uppsala University, ; Uppsala, Sweden
                [7 ]GRID grid.413253.2, Department of Pediatrics, , Ryhov County Hospital, ; Jonkoping, Sweden
                [8 ]ISNI 0000 0000 9919 9582, GRID grid.8761.8, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, , University of Gothenburg, ; Gothenburg, Sweden
                [9 ]ISNI 0000 0004 0512 597X, GRID grid.154185.c, Department of Pediatrics, , Aarhus University Hospital, ; Aarhus, Denmark
                [10 ]GRID grid.475435.4, Department of Pediatrics, , Rigshospitalet Copenhagen University Hospital, ; Copenhagen, Denmark
                [11 ]ISNI 0000 0004 0627 3560, GRID grid.52522.32, Department of Pediatrics, , St. Olavs Hospital, ; Trondheim, Norway
                [12 ]ISNI 0000000122595234, GRID grid.10919.30, Department of Mathematics and Statistics, , UIT the Arctic University of Norway, ; Tromsø, Norway
                Author information
                http://orcid.org/0000-0003-3476-305X
                Article
                1571
                10.1186/s13075-018-1571-6
                5934822
                29724248
                19034320-275d-4880-b067-7254aef018b7
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 25 January 2018
                : 16 March 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007137, Helse Nord RHF;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2018

                Orthopedics
                juvenile idiopathic arthritis,disease activity,prediction,outcome research
                Orthopedics
                juvenile idiopathic arthritis, disease activity, prediction, outcome research

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