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.
Project LeadN Wulffraat
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 (nih.gov) . 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, Krol RM, Giancane G, Panaviene V, Ailioaie LM, Doležalová P, Cattalini M, Susic G, Sztajnbok F, Maritsi D, Constantin T, Sawhney S, Rygg M, Oliveira SK, Nordal EB, Saad-Magalhaes C, Rubio-Perez N, Jelusic M, de Roock S, Wulffraat NM, Ruperto N, Swart JF; Paediatric Rheumatology International Trials Organisation (PRINTO). Increased incidence of inflammatory bowel disease on etanercept in juvenile idiopathic arthritis regardless of concomitant methotrexate use. Rheumatology (Oxford). 2021 Sep 11:keab678. doi: 10.1093/rheumatology/keab678. Epub ahead of print. PMID: 34508559.
van Straalen, J. W., Giancane, G., Amazrhar, Y., Tzaribachev, N., Lazar, C., Uziel, Y., Telcharova-Mihaylovska, A., Len, C. A., Miniaci, A., Boteanu, A. L., Filocamo, G., Mastri, M. V., Arkachaisri, T., Magnolia, M. G., Hoppenreijs, E., de Roock, S., Wulffraat, N. M., Ruperto, N., Swart, J. F., & Paediatric Rheumatology International Trials Organisation (PRINTO) (2021). A clinical prediction model for estimating the risk of developing uveitis in patients with juvenile idiopathic arthritis. Rheumatology (Oxford, England), 60(6), 2896–2905. https://doi.org/10.1093/rheumatology/keaa733