OBJECTIVE: To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist. METHODS: The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability. RESULTS: The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years. CONCLUSION: The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.

5 A Nasonova Research Institute of Rheumatology Moscow Russia

Charles University Prague and General University Hospital Prague Czech Republic

Children's Hospital Affiliate of Vilnius University Hospital Santaros Clinic and Clinic of Children's Diseases Vilnius University Vilnius Lithuania

Istituto Giannina Gaslini IRCCS and Clinica Pediatrica e Reumatologia Genoa Italy

Meir Medical Centre and Kfar Saba and Sackler School of Medicine Tel Aviv University Tel Aviv Israel

National Institute of Geriatrics Rheumatology and Rehabilitation Warsaw Poland

New Children's Hospital and Helsinki University Hospital Helsinki Finland

Pavol Jozef Šafárik University in Košice Kosice Slovakia

Ramathibodi Hospital and Mahidol University Bangkok Thailand

Seattle Children's Hospital Seattle Washington

Tartu University Hospital Children's Clinic and University of Tartu Institute of Clinical Medicine Tartu Estonia

Università degli Studi di Genova Genoa Italy

Università degli Studi di Genova Istituto Giannina Gaslini IRCCS and Clinica Pediatrica e Reumatologia Genoa Italy

Università degli Studi di Genova Istituto Giannina Gaslini IRCCS and Clinica Pediatrica e Reumatologia Genoa Italy and Sechenov 1st Moscow State Medical University Moscow Russia

Université Paris Descartes Institut IMAGINE Centre de Référence National pour les Rhumatismes Inflammatoires et les Maladies Auto Immunes Systémiques Rares de l'Enfant Hôpital Necker Enfants Malades AP HP Paris France

University Children's Hospital and University Medical Centre Ljubljana Ljubljana Slovenia

Wilhelmina Children's Hospital Utrecht The Netherlands

Wilhelmina Children's Hospital Utrecht The Netherlands and Istituto Giannina Gaslini IRCCS and Clinica Pediatrica e Reumatologia Genoa Italy

See more in PubMed

Ravelli A, Martini A. Juvenile idiopathic arthritis [review]. Lancet 2007;369:767–78. PubMed

Viola S, Felici E, Magni‐Manzoni S, Pistorio A, Buoncompagni A, Ruperto N, et al. Development and validation of a clinical index for assessment of long‐term damage in juvenile idiopathic arthritis. Arthritis Rheum 2005;52:2092–102. PubMed

Brunner HI, Higgins GC, Wiers K, Lapidus SK, Olson JC, Onel K, et al. Health‐related quality of life and its relationship to patient disease course in childhood‐onset systemic lupus erythematosus. J Rheumatol 2009;36:1536–45. PubMed

Duffy CM. Measurement of health status, functional status, and quality of life in children with juvenile idiopathic arthritis: clinical science for the pediatrician. Pediatr Clin North Am 2005;52:359–72. PubMed

Bartoli M, Taro M, Magni‐Manzoni S, Pistorio A, Traverso F, Viola S, et al. The magnitude of early response to methotrexate therapy predicts long‐term outcome of patients with juvenile idiopathic arthritis. Ann Rheum Dis 2008;67:370–4. PubMed

Albers HM, Brinkman DM, Kamphuis SS, Van Suijlekom‐Smit LW, Van Rossum MA, Hoppenreijs EP, et al. Clinical course and prognostic value of disease activity in the first two years in different subtypes of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2010;62:204–12. PubMed

Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni‐Manzoni S, Filocamo G, et al. Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum 2009;61:658–66. PubMed

Nordal EB, Zak M, Aalto K, Berntson L, Fasth A, Herlin T, et al. Validity and predictive ability of the juvenile arthritis disease activity score based on CRP versus ESR in a Nordic population‐based setting. Ann Rheum Dis 2012;71:1122–7. PubMed

McErlane F, Beresford MW, Baildam EM, Chieng SE, Davidson JE, Foster HE, et al. Validity of a three‐variable Juvenile Arthritis Disease Activity Score in children with new‐onset juvenile idiopathic arthritis. Ann Rheum Dis 2013;72:1983–8. PubMed PMC

Aletaha D, Ward MM, Machold KP, Nell VP, Stamm T, Smolen JS. Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 2005;52:2625–36. PubMed

Consolaro A, Bracciolini G, Ruperto N, Pistorio A, Magni‐Manzoni S, Malattia C, et al. Remission, minimal disease activity, and acceptable symptom state in juvenile idiopathic arthritis: defining criteria based on the juvenile arthritis disease activity score. Arthritis Rheum 2012;64:2366–74. PubMed

Consolaro A, Ruperto N, Bracciolini G, Frisina A, Gallo MC, Pistorio A, et al. Defining criteria for high disease activity in juvenile idiopathic arthritis based on the juvenile arthritis disease activity score. Ann Rheum Dis 2014;73:1380–3. PubMed

Consolaro A, Negro G, Gallo MC, Bracciolini G, Ferrari C, Schiappapietra B, et al. Defining criteria for disease activity states in nonsystemic juvenile idiopathic arthritis based on a three‐variable juvenile arthritis disease activity score. Arthritis Care Res (Hoboken) 2014;66:1703–9. PubMed

Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, for the Childhood Arthritis Rheumatology Research Alliance (CARRA), the Pediatric Rheumatology Collaborative Study Group (PRCSG), and the Paediatric Rheumatology International Trials Organisation (PRINTO) . American College of Rheumatology provisional criteria for defining clinical inactive disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2011;63:929–36. PubMed

Magni‐Manzoni S, Ruperto N, Pistorio A, Sala E, Solari N, Palmisani E, et al. Development and validation of a preliminary definition of minimal disease activity in patients with juvenile idiopathic arthritis. Arthritis Rheum 2008;59:1120–7. PubMed

Consolaro A, Giancane G, Alongi A, van Dijkhuizen EH, Aggarwal A, Al‐Mayouf SM, et al. Phenotypic variability and disparities in treatment and outcomes of childhood arthritis throughout the world: an observational cohort study. Lancet Child Adolesc Health 2019;3: 255–63. PubMed

Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 2004;31:390–2. PubMed

Ravelli A, Davi S, Bracciolini G, Pistorio A, Consolaro A, van Dijkhuizen EH, et al. Intra‐articular corticosteroids versus intra‐articular corticosteroids plus methotrexate in oligoarticular juvenile idiopathic arthritis: a multicentre, prospective, randomised, open‐label trial. Lancet 2017;389:909–16. PubMed

Ruperto N, Lovell DJ, Quartier P, Paz E, Rubio‐Perez N, Silva CA, et al. Abatacept in children with juvenile idiopathic arthritis: a randomised, double‐blind, placebo‐controlled withdrawal trial. Lancet 2008;372:383–91. PubMed

Swart J, Giancane G, Horneff G, Magnusson B, Hofer M, Alexeeva E, et al. Pharmacovigilance in juvenile idiopathic arthritis patients treated with biologic or synthetic drugs: combined data of more than 15,000 patients from Pharmachild and national registries. Arthritis Res Ther 2018;20:285. PubMed PMC

López‐Ratón M, Rodríguez‐Álvarez M, Cadarso‐Suárez C, Gude‐Sampedro F. OptimalCutpoints: an R package for selecting optimal cutpoints in diagnostic tests. J Stat Softw 2014;61:v06i08.

Youden WJ. Index for rating diagnostic tests. Cancer 1950;3:32–5. PubMed

Ruopp MD, Perkins NJ, Whitcomb BW, Schisterman EF. Youden Index and optimal cut‐point estimated from observations affected by a lower limit of detection. Biom J 2008;50:419–30. PubMed PMC

Perkins NJ, Schisterman EF. The inconsistency of "optimal" cutpoints obtained using two criteria based on the receiver operating characteristic curve. Am J Epidemiol 2006;163:670–5. PubMed PMC

Machado P, Landewe R, Lie E, Kvien TK, Braun J, Baker D, et al. Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut‐off values for disease activity states and improvement scores. Ann Rheum Dis 2011;70:47–53. PubMed

Filocamo G, Sztajnbok F, Cespedes‐Cruz A, Magni‐Manzoni S, Pistorio A, Viola S, et al. Development and validation of a new short and simple measure of physical function for juvenile idiopathic arthritis. Arthritis Rheum 2007;57:913–20. PubMed

Giannini EH, Ruperto N, Ravelli A, Lovell DJ, Felson DT, Martini A. Preliminary definition of improvement in juvenile arthritis. Arthritis Rheum 1997;40:1202–9. PubMed

Swart JF, van Dijkhuizen EH, Wulffraat NM, de Roock S. Clinical Juvenile Arthritis Disease Activity Score proves to be a useful tool in treat‐to‐target therapy in juvenile idiopathic arthritis. Ann Rheum Dis 2018;77:336–42. PubMed PMC

Tibaldi J, Pistorio A, Aldera E, Puzone L, El Miedany Y, Pal P, et al. Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 2020;59:3505–14. PubMed

Clinical insights into heterogeneity of rheumatoid factor negative polyarticular juvenile idiopathic arthritis across the world

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