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      Criteria Associated with Treatment Decisions in Juvenile Idiopathic Arthritis with a Focus on Ultrasonography: Results from the JIRECHO Cohort

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          Abstract

          Background

          The treatment of children with juvenile idiopathic arthritis (JIA) to prevent disability is a major challenge in paediatric rheumatology. The presence of synovitis, which is difficult to detect in children, is associated with structural damage. Musculoskeletal ultrasonography (MSUS) can be used in patients with JIA to reveal subclinical synovitis.

          Objective

          The primary aim was to determine whether the use of MSUS was associated with therapeutic modification in patients with JIA. The secondary aim was to identify other factors associated with therapeutic decisions.

          Methods

          We conducted an observational study based on the JIRECHO multi-centre cohort, which was developed to provide a systematic MSUS follow-up for patients with JIA. Follow-up occurred every 6 months and included clinical and MSUS examinations. We included children who underwent MSUS of the elbows, wrists, second metacarpophalangeal joints, knees and ankles, which was performed by expert sonographers. Clinical and biological data, disease activity scores and information on therapeutics were collected.

          Results

          A total of 185 visits concerning 112 patients were recorded. Three groups were defined according to the therapeutic decision: escalation (22%, n = 40), de-escalation (14%, n = 26) or stable (64%, n = 119). In the “therapeutic escalation” group: the presence of ultrasonographic synovitis in B-mode and the presence of grade 2 or 3 synovitis in B-mode were not significantly more frequent than in the “stable therapeutic or de-escalation” group (80% versus 65%, p = 0.06; 33% versus 19%, p = 0.06), and the patient’s and physician’s visual analogue scale (VAS) scores, the clinical JADAS and the C-reactive protein level were significantly higher, but only physician’s VAS score remained in the model of logistic regression. In the “therapeutic de-escalation” group: there was no difference in the presence of US synovitis compared with the “stable therapeutic or escalation” group (62% versus 69%, p = 0.48).

          Conclusion

          Even though US synovitis tended to be more frequent in patients with therapeutic escalation, the study did not show that the presence of synovitis in MSUS was statistically associated with therapeutic modifications in patients with JIA. Treatment remained stable despite the presence of US synovitis.

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          Most cited references28

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          International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001.

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            Juvenile idiopathic arthritis.

            Juvenile idiopathic arthritis is a heterogeneous group of diseases characterised by arthritis of unknown origin with onset before age of 16 years. Pivotal studies in the past 5 years have led to substantial progress in various areas, ranging from disease classification to new treatments. Gene expression profiling studies have identified different immune mechanisms in distinct subtypes of the disease, and can help to redefine disease classification criteria. Moreover, immunological studies have shown that systemic juvenile idiopathic arthritis is an acquired autoinflammatory disease, and have led to successful studies of both interleukin-1 and interleukin-6 blockade. In other forms of the disease, synovial inflammation is the consequence of a disturbed balance between proinflammatory effector cells (such as T-helper-17 cells), and anti-inflammatory regulatory cells (such as FOXP3-positive regulatory T cells). Moreover, specific soluble biomarkers (S100 proteins) can guide individual treatment. Altogether these new developments in genetics, immunology, and imaging are instrumental to better define, classify, and treat patients with juvenile idiopathic arthritis. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Development and validation of a composite disease activity score for juvenile idiopathic arthritis.

              To develop and validate a composite disease activity score for juvenile idiopathic arthritis (JIA), the Juvenile Arthritis Disease Activity Score (JADAS). The JADAS includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. These variables are part of the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, and Pedi 70 criteria for improvement. Validation analyses were conducted on >4,500 patients and included assessment of construct validity, discriminant validity, and responsiveness to change. Three versions of the JADAS were tested based on 71-joint (range 0-101), 27-joint (range 0-57), or 10-joint (range 0-40) counts. Statistical performances of the JADAS were compared with those of 2 rheumatoid arthritis composite scores, the Disease Activity Score in 28 joints (DAS28) and the Clinical Disease Activity Index (CDAI). The JADAS demonstrated good construct validity, yielding strong correlations with JIA activity measures not included in the score and moderate correlations with the Childhood Health Assessment Questionnaire. Correlations obtained for the 3 JADAS versions were comparable, but superior to those yielded by the DAS28 and CDAI. The area under the curve of the JADAS predicted long-term disease outcome, measured as radiographic progression over 3 years. In 2 clinical trials, the JADAS discriminated well between ACR Pedi 30, Pedi 50, and Pedi 70 response and revealed strong responsiveness to clinical change. The JADAS was found to be a valid instrument for assessment of disease activity in JIA and is potentially applicable in standard clinical care, observational studies, and clinical trials.
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                Author and article information

                Contributors
                alain.saraux@chu-brest.fr
                Journal
                Rheumatol Ther
                Rheumatol Ther
                Rheumatology and Therapy
                Springer Healthcare (Cheshire )
                2198-6576
                2198-6584
                23 November 2022
                23 November 2022
                : 1-14
                Affiliations
                [1 ]Department of Rheumatology, CHU Brest, Brest University, Inserm, LBAI, UMR1227, Brest, France
                [2 ]GRID grid.413784.d, ISNI 0000 0001 2181 7253, Department of Pediatric Rheumatology, National Reference Centre for Auto-Inflammatory Diseases and Amyloidosis of Inflammatory Origin (CEREMAIA), , Bicêtre Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), ; Le Kremlin Bicêtre, France
                [3 ]GRID grid.150338.c, ISNI 0000 0001 0721 9812, Pediatric Immuno-Rheumatology of Western Switzerland, Department Women-Mother-Child, , Lausanne University Hospital, Lausanne, and University Hospital, ; Geneva, Switzerland
                [4 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Service d’immunologie, Hématologie, Rhumatologie Pédiatriques, , Hôpital Necker-Enfants-Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), ; Paris, France
                [5 ]GRID grid.412134.1, ISNI 0000 0004 0593 9113, Service de Radiologie Pédiatrique, , Hôpital Necker-Enfants-Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), ; Paris, France
                [6 ]GRID grid.414085.c, ISNI 0000 0000 9480 048X, Service de Rhumatologie, , CH de Mulhouse, ; Mulhouse, France
                [7 ]GRID grid.413745.0, ISNI 0000 0001 0507 738X, Servcice de Pédiatrie Générale, Infectieux et Immunologie Clinique, , Hôpital Arnaud de Villeneuve, ; Montpellier, France
                [8 ]GRID grid.157868.5, ISNI 0000 0000 9961 060X, Rheumatology Department, , CHU Montpellier, Montpellier University, ; Montpellier, France
                [9 ]GRID grid.411766.3, ISNI 0000 0004 0472 3249, Rheumatology Unit, Hôpital de la Cavale Blanche, ; BP 824, 29609 Brest Cedex, France
                Author information
                http://orcid.org/0000-0002-8454-7067
                Article
                512
                10.1007/s40744-022-00512-2
                9702887
                36427176
                d5ed686e-a366-4112-96b3-2f12eebab54d
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 26 September 2022
                : 7 November 2022
                Categories
                Original Research

                juvenile idiopathic arthritis,ultrasonography,synovitis,therapeutic decision,treatment

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