Prediction of unfavorable outcome in Juvenile Idiopathic Arthritis (JIA) and assessment of the long-term outcomes in JIA-associated uveitis – A prospective Nordic multicenter study of JIA from childhood to adulthood

Juvenile idiopathic arthritis (JIA) is a chronic childhood disease with joint inflammation as the main feature. The course and outcomes are heterogeneous with a large span in disease severity. There is increasing evidence that early aggressive treatment may modify the disease course in JIA. Precise determination of disease prognosis is therefore sought to guide early decisions on which children need disease modifying anti-rheumatic drugs (DMARDs) and biologics. We aimed to develop and validate clinically applicable models for the prediction of unfavorable outcomes in JIA. The goal was to improve JIA outcomes by providing a practical application to support clinicians in treatment decisions. We collaborated with Canadian researchers who separately had developed a model for predicting severe disease course. We developed a multivariable logistic regression model with eight clinical variables in the Nordic JIA cohort. The model performed well in predicting non-achievement of remission (the Nordic outcome), both in internal validation and in external validation in the Canadian cohort. We externally validated the Canadian model in the Nordic cohort yielding an excellent predictive ability. The Nordic model performed almost equally as well without blood tests and also performed well in predicting severe disease course (the Canadian outcome). The Canadian model did not attain an acceptable prediction of the Nordic outcome. Uveitis is the most common extraarticular manifestation of JIA and may lead to severe sight-threatening complications. We found a high cumulative incidence of uveitis in 96 of 434 children (22%) in the Nordic cohort. Ocular complications, mainly cataract and glaucoma, were present in 39% of the young adults with uveitis at follow-up 18 years after onset of JIA. Predictors associated with development of ocular complications were uveitis before JIA, short interval between JIA and uveitis, and ANA positivity. Our results strongly suggest early and tight eye screening programs and close collaboration between ophthalmologists and pediatric rheumatologists for optimal treatment to minimize long-term complications

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

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

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

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.Peer reviewe

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

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.Peer reviewe

Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis : a longitudinal study of the Nordic JIA cohort

Abstract Background To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status. Methods A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed. Results In total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline. None of the protein levels had prognostic abilities for remission status 17 years after disease onset. Conclusion We hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation

Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis : a longitudinal study of the Nordic JIA cohort

Background To determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status. Methods A population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed. Results In total, 293 patients with JIA were included (mean age 23.7 +/- 4.4 years; mean follow-up 17.2 +/- 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (pPeer reviewe

Incidence and predictors of Uveitis in juvenile idiopathic arthritis in a Nordic long-term cohort study

Background: The incidence of uveitis associated with juvenile idiopathic arthritis (JIA) varies around the world. Our aim was to investigate the incidence and predictors of uveitis in a Nordic population-based cohort. Methods: Consecutive JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis. Results: Uveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range - 4.7 to 9.4) years after onset of arthritis. Predictors of uveitis were age 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p <0.001), but not in boys (p = 0.390). Conclusion: Early-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.Peer reviewe

Transitioning patients with juvenile idiopathic arthritis to adult care : the Nordic experience

Background With juvenile idiopathic arthritis (JIA), there are several protocols and practices used worldwide for the transition from paediatric to adult care. In this study, we examined the transferral rates and disease activity after transition, as well as the disease- and health-related outcomes. We also introduce the transition practices employed in the Nordic countries. Methods The study population comprised 408 participants with a disease onset from 1997 to 2000 who attended an 18-year follow-up visit in this population-based Nordic JIA cohort study. The patients were retrospectively divided into three subgroups: Patients transferred directly from paediatric care to adult rheumatology care, patients referred there later, and patients never transferred during the 18-year follow-up period. Results One hundred and sixty-three (40%) JIA patients had been directly transferred to an adult clinic. The cumulative transition rate was 52%, but there were significant differences between the participating centres. Fifty patients had later been referred to an adult clinic. Among the 195 patients who had never been transferred, 39% were found to have disease activity at the study visit. Conclusion This study highlights the need to reconsider transition practices to avoid our undesirable finding of patients with disease activity in JIA, but no appropriate health care follow-up.Peer reviewe

Participation in school and physical education in juvenile idiopathic arthritis in a Nordic long-term cohort study

BackgroundThe aim of the study was to describe school attendance and participation in physical education in school among children with juvenile idiopathic arthritis (JIA).MethodsConsecutive cases of JIA from defined geographical areas of Finland, Sweden and Norway with disease onset in 1997 to 2000 were followed for 8 years in a multi-center cohort study, aimed to be as close to population-based as possible. Clinical characteristics and information on school attendance and participation in physical education (PE) were registered.ResultsParticipation in school and in PE was lowest initially and increased during the disease course. Eight years after disease onset 228/274 (83.2%) of the children reported no school absence due to JIA, while 16.8% reported absence during the last 2 months due to JIA. Full participation in PE was reported by 194/242 (80.2%), partly by 16.9%, and none by 2.9%. Lowest participation in PE was found among children with ERA and the undifferentiated categories. Absence in school and PE was associated with higher disease activity measures at the 8-year visit. School absence >1day at baseline predicted use of disease-modifying anti-rheumatic drugs, including biologics (DMARDs) (OR 1.2 (1.1-1.5)), and non-remission off medication (OR 1.4 (1.1-1.7) 8 years after disease onset.ConclusionSchool absence at baseline predicted adverse long-term outcome. In children and adolescents with JIA participation in school activities is mostly high after 8years of disease. For the minority with low participation, special attention is warranted to promote their full potential of social interaction and improve long-term outcome.Peer reviewe