Comorbidity in Juvenile Idiopathic Arthritis (JIA)


Comorbidity can be defined as the presence of two disorders or more occurring at the same time in a single patient. Children with chronic diseases such as JIA can develop complications of the disease itself, a new disease or drug related side effects that have a significant impact on the quality of life. In this project we want to study all significant events occurring before or after the onset of arthritis.

Facts and Figures

Project Lead
N Wulffraat
UMC Utrecht
FOREUM research grant: € 300.000

Meet the Team

Project Lead

N Wulffraat
UMC Utrecht
J Swart
UMC Utrecht
K Hyrich
University of Manchester
M Lunt
University of Manchester
L Kearsley-Fleet
University of Manchester
N Ruperto
Istituto Giannina Gaslini
G Giancane
IRCCS Istituto G. Gaslini
K Minden
Charité Berlin
J Klotsche
Charité Berlin
G Horneff
Charité Berlin
W Costello
European Network for Children with Arthritis ENCA
C Schoemaker
Dutch JIA parent organisation

Final Results

  • Demographics of JIA patients. Metrics to measure success: compare with 2015 demographics, % recruited at onset of JIA, % recruited at start of therapy ( MTX, or Biologic).
  • Description of comorbidities, frequency of follow up, degree of missing data, analysis of correlation with multipara meters such as medication, disease duration, subtype.
  • Prepare an evaluation plan for further analysis of the severity of these comorbidities and their impact on the quality of life
  • Establish durable collaboration between the registries

Lay Summary

Firstly the group investigated the comorbidities in eight-thousand children and young people with JIA across three large registers. This analysis is the first and largest to investigate the occurrence of four important comorbidities and the role of anti-rheumatic drugs. Combined, these three registries represent one of the largest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies. Rates of comorbidities were similar, although varicella vaccination in populations impacted comparability of varicella infections. With this article the group showed how JIA registers can collaborate.
The most common comorbid condition in JIA patients is an eye inflammation also called uveitis (JIA-U). While screening for JIA-U is of utmost importance, there is no international consensus on screening frequency and criteria, leaving clinicians with a large gap open for their own interpretation. Individual risk estimates for developing JIA-U were still unavailable to date. An individualized prediction model for JIA-U for clinical application WAS developed. With this it is possible to provide a guidance tool for clinicians and patients and parents to individually estimate the probability of uveitis occurring in newly diagnosed JIA patients. This article is free available online A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis - PubMed ( . Subsequently a model that predicts the risk for uveitis for an individual JIA patient after 2, 4 and 7 years of disease duration was developed. The robustness of this model was confirmed by using the data of our 3 separate cohorts in FOREUM. Risk estimates following our prediction model could be used to inform patients/parents and provide guidance in choice of uveitis screening frequency and arthritis drug therapy with the possible extra aim of preventing the onset of uveitis.
Furthermore it was looked into the role of immunosuppressive drugs in the development of inflammatory bowel disease (IBD) in children with JIA. Although it is rare, it occurs more often than in the general pediatric population and has a significant negative impact on quality of life. The group analysed the largest group of IBD development in JIA patients with 48 included cases. It was found that the 48 IBD cases in JIA are associated with enthesitis-related arthritis, a positive family history of autoimmune disease(s) and etanercept therapy (regardless if combined with methotrexate).
Given the results of this study, it might be recommended to use adalimumab instead of etanercept as the biologic of first choice in ERA patients with a positive family history of autoimmune disease(s).
A durable collaboration between the registries was established and it is expect more studies to be performed together.


  • Van Straalen JW, Kearsley-Fleet L, Klotsche J, De Roock S, Minden K, Heiligenhaus A, Hyrich KL, De Boer JH, Lamot L, Olivieri AN, Gallizzi R, Smolewska E, Faugier E, Pastore S, Hashkes PJ, Herrera CN, Emminger W, Consolini R, Wulffraat NM, Ruperto N, Swart JF. Development and external validation of a prognostic prediction model for chronic uveitis in juvenile idiopathic arthritis. Arthritis & Rheumatology (IF=15.483 in 2021). 23 August 2022
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  • Van Straalen JW, de RoockS, Giancane G, Alexeeva E, Koskova E, Mesa-del-Castillo P, Zulian F, Civino A, Montin D, Wulffraat NM, Ruperto N, Swart JF. Prevalence of familial autoimmunity in juvenile idiopathic arthritis: results from the international Pharmachild registry. Pediatr Rheumatol. (IF=3.413 in 2021) Nov 2022 20:103.
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  • van Straalen JW, Krol RM, Giancane G, Panaviene V, Ailioaie C, Dolezalova P, Cattalini M, Susic G, Sztajnbok F, Maritsi D, Constantin T, Sawhney S, Rygg M, Oliveira SK, Nordal EB, Magalhaes CS, Rubio-Perez N, Jelusic M, de Roock S, Wulffraat NM, Ruperto N, Swart JF. Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use. Rheumatology (Oxford) (IF=7.046) 2021. Sep 11:keab678. doi: 10.1093/rheumatology/keab678.
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  • Kearsley-Fleet L, Klotsche J, van Straalen JW, Costello W, D’Angelo G, Giancane G, Horneff G, Klein A, Láday M, Lunt M, de Roock S, Ruperto N, Schoemaker C, Vijatov-Djuric G, Vojinovic J, Vougiouka O, Wulffraat NM, Hyrich KL, Minden K, Swart JF. Burden of comorbid conditions in children and young people with juvenile idiopathic arthritis: a collaborative analysis of 3 JIA registries Rheumatology (Oxford). (IF=7.046) 2021 Oct 6;keab641. doi: 10.1093/rheumatology/keab641.
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  • van Straalen JW, Giancane G, Amazrhar Y, Tzaribachev N, Lazar C, Uziel Y, Telcharova-Mihaylovska A, Len CA, Miniaci A, Boteanu AL, Filocamo G, Mastri MV, Arkachaisri T, Magnolia MG, Hoppenreijs E, de Roock S, Wulffraat NM, Ruperto N, Swart JF. A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford). (IF=7.046) 2021 Jun 18;60(6):2896-2905. doi: 10.1093/rheumatology/keaa733.
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EULAR Abstracts


  • OP0058: Development of inflammatory bowel disease during treatment with Etanercept in patients with Juvenile Idiopathic Arthritis; Roline Krol, Joost F. Swart, Gabriella Giancane, Sytze De Roock, Troels Herlin, Pavla Dolezalova, Helga Sanner, Gordana Susic, Flávio R. Sztajnbok, D Maritsi, Tamas Constantin, V Vargova, Sujata Sawhney, Marite Rygg, Sheila Knupp D.E. Oliveira, Marco Cattalini, Ellen Norda, Claudia Magalhaes, Alberto Martini, Nico Wulffraat, Nicolino Ruperto
    Go to EULAR Abstract Archive

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