Disease control and health‐related quality of life in juvenile idiopathic arthritis

Objective

To examine variability in health‐related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA) experiencing no or minimal clinical symptoms, and in a subgroup with polyarticular JIA treated with biologic agents for 12 months.

Methods

We defined 3 samples using a database of patients ages 2–18 years with JIA (n = 524; patient visits [PV] = 2,354): visits (PV = 2,155) with no or minimal clinical symptoms on at least 1 of 4 measures (active joint count, pain, physician global disease rating, Childhood Health Assessment Questionnaire); visits (PV = 941) with no or minimal symptoms on all 4 measures; and children (n = 31) with polyarticular JIA treated with biologic agents for 12 months. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL) and the percentage of patients with suboptimal HRQOL was determined.

Results

In PV with a PedsQL score, suboptimal HRQOL by self‐report occurred in 362 (20.6%) PV with at least 1 indicator of minimal symptoms, and in 64 (7.9%) PV with all 4 measures indicating minimal symptoms (519 [25.7%] and 95 [10.7%], respectively, by parent report). For children with polyarticular JIA treated for 12 months with biologic agents, 7 (25.9%) patients by self‐report and 10 (35.7%) patients by parent report were in the suboptimal range of HRQOL.

Conclusion

A substantial percentage of patients with JIA who report no or mild clinical symptoms experience suboptimal HRQOL. This is also true for patients with polyarticular JIA treated with biologic agents for 12 months. Although disease activity and clinical symptoms are related to HRQOL, considerable unexplained variation in HRQOL exists. HRQOL needs to be assessed independently regardless of clinical status.

     

Genetic loci contributing to hemophagocytic lymphohistiocytosis do not confer susceptibility to systemic‐onset juvenile idiopathic arthritis

Objective

To investigate whether single‐nucleotide polymorphisms (SNPs) within the genes PRF1, GZMB, UNC13D, and Rab27a, which are involved in natural killer cell dysfunction and known to contribute to the risk of hemophagocytic lymphohistiocytosis (HLH), confer an increased risk of susceptibility to systemic‐onset juvenile idiopathic arthritis (JIA).

Methods

Four SNPs across the PRF1 gene locus, 5 for GZMB, 7 for UNC13D, and 11 for Rab27a were investigated using MassArray genotyping in 133 UK Caucasian patients with systemic‐onset JIA and 384 ethnically matched unrelated control subjects. Additional control genotypes were accessed from the data generated by the Wellcome Trust Case Control Consortium.

Results

No significant association was found between any SNP within the 4 selected loci and systemic‐onset JIA, by either single‐point or haplotype analysis.

Conclusion

The results of this study demonstrate that genes involved in HLH do not confer a significant risk of association with systemic‐onset JIA.

     

Feasibility and construct validity of the parent willingness‐to‐pay technique for children with juvenile idiopathic arthritis

Objective

To assess the feasibility and construct validity of the willingness‐to‐pay (WTP) technique for measuring health care preferences in families of children with juvenile idiopathic arthritis (JIA).

Methods

Parents were asked to estimate the monthly US dollar amount they would be willing to pay to obtain for their child the following hypothetical drugs: ARTHRO, which guarantees complete clinical response; and NO‐STOM‐ACHE, a drug that eliminates gastrointestinal (GI) symptoms. A yes/no question was used with random assignment of the starting bids. Parents who agreed to pay the starting bid were then asked whether they would be willing to pay 200% and then 400% of this initial bid. Socioeconomic data and information on medications, disease activity, patient physical function, wellbeing, and health‐related quality of life (HRQOL) were obtained.

Results

Sixty‐two families of children with JIA were interviewed. GI symptoms were present in 54%, and 53% of the children had joints with active arthritis or limited range of motion. Four parents (7%) were unwilling to pay anything for any of the studied medications. The mean amount (median; mean percentage of available family income) families were willing to pay was $395 ($300; 15%) for ARTHRO and $109 ($80; 4%) for NO‐STOM‐ACHE. Correlation and regression analysis supported that, adjusted for the available family income, the WTP for ARTHRO was associated with disease activity, pain, and the HRQOL of the patients. After correction for the starting bids and the available family income, the WTP for NO‐STOM‐ACHE was associated with the patient's HRQOL, pain, and the amount of GI discomfort.

Conclusion

The WTP technique is feasible and has construct validity for measuring health care preferences for children with JIA. Relatively large WTP estimates support a possible important negative impact of the disease on families of children with JIA.

     

Abatacept improves health‐related quality of life,pain, sleep quality,and daily participation in subjects with juvenile idiopathic arthritis

Objective

To assess health‐related quality of life (HRQOL) in abatacept‐treated children/adolescents with juvenile idiopathic arthritis (JIA).

Methods

In this phase III, double‐blind, placebo‐controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to ≥1 disease‐modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4‐month open‐label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined “responders”) were randomized to abatacept or placebo (plus MTX) in the 6‐month double‐blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100‐mm visual analog scale), the Children's Sleep Habits Questionnaire, and a daily activity participation questionnaire.

Results

A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept‐treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents' usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus ?1.3 [P = 0.109] school days/month and parents' usual activity days/month, respectively, in abatacept‐ versus placebo‐treated subjects).

Conclusion

Improvements in HRQOL were observed with abatacept, providing real‐life tangible benefits to children with JIA and their parents/caregivers.

     

Impact of fatigue on health‐related quality of life in rheumatoid arthritis

Objective

To multidimensionally assess fatigue in rheumatoid arthritis (RA) and to evaluate the impact of fatigue on health‐related quality of life (HRQOL).

Methods

The study was conducted in 1999 among 490 RA patients with varying disease duration. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI‐20) and HRQOL with a validated Dutch version of the RAND 36‐Item Health Survey. We evaluated the impact of fatigue on HRQOL by multiple linear regression analyses taking into account RA‐related pain and depressive symptoms.

Results

Different aspects of fatigue selectively explained different dimensions of HRQOL. The MFI‐20 was entered last to the linear regression models, resulting in an additional increase of explained variance of 1% (mental health) to 14% (vitality).

Conclusion

The multidimensional portrayal of RA‐related fatigue can be used to develop intervention strategies targeted to specific aspects of fatigue. Fatigue, supplementary to RA‐related pain and depressive symptoms, appears to be a feasible and treatable target in the clinical management of RA to increase HRQOL.

     

Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis

Objective

To investigate the involvement of candidate cytokine genes in the pathogenesis of juvenile idiopathic arthritis (JIA).

Methods

Single nucleotide polymorphisms and intragenic microsatellite markers within 8 candidate cytokine genes (interleukin‐1α [IL‐1α], IL‐2, IL‐4, IL‐6, IL‐10, interferon‐α1 [IFNA1], interferon‐γ [IFNG], and interferon regulatory factor 1 [IRF‐1]) were investigated in 417 Caucasian patients with clinically characterized JIA and a panel of 276 unrelated, healthy Caucasian controls, all from the United Kingdom.

Results

A novel 3′–untranslated region (3′UTR) polymorphism in IRF‐1 was found to be associated with susceptibility to JIA (corrected P = 0.002). No significant association with IL‐1α, IL‐2, IL‐4, IL‐6, IL‐10, IFNA1, or IFNG was observed.

Conclusion

An association between JIA and a previously unreported 3′UTR polymorphism of IRF‐1 was observed. This association was not found to be specific to any particular JIA subgroup. This suggests that IRF‐1 may contribute to a common pathogenesis shared by all JIA patients, regardless of clinical phenotype. This is most likely to be a genetic contribution to the chronic inflammatory process that underlies JIA pathology.

     

Quality of well‐being in older people with osteoarthritis

Objective

To examine the sensitivity of the Quality of Well‐Being Scale (QWB) as a measure of health‐related quality of life (HRQOL) in people with osteoarthritis (OA).

Methods

The QWB was administered, along with the Arthritis Impact Measurement Scale (AIMS) and other health measures. Health care utilization data were also obtained.

Results

People with OA had a mean QWB score of 0.643. The QWB scores were significantly correlated with total AIMS scores, self‐rated health status, health care costs, depression scores, and most AIMS subscales. In addition, changes in QWB scores after 1 year were significantly correlated with changes in total AIMS scores and some AIMS subscales.

Conclusion

The QWB appears to be a useful and sensitive generic, utility‐based measure of HRQOL in people with OA.

     

Identification of a novel susceptibility locus for juvenile idiopathic arthritis by genome‐wide association analysis

Objective

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease of childhood. Two well‐established genetic factors known to contribute to JIA susceptibility, HLA and PTPN22, account for less than half of the genetic susceptibility to disease; therefore, additional genetic factors have yet to be identified. The purpose of this study was to perform a systematic search of the genome to identify novel susceptibility loci for JIA.

Methods

A genome‐wide association study using Affymetrix GeneChip 100K arrays was performed in a discovery cohort (279 cases and 184 controls). Single‐nucleotide polymorphisms (SNPs) showing the most significant differences between cases and controls were then genotyped in a validation sample of cases (n = 321) and controls, combined with control data from the 1958 UK birth cohort (n = 2,024). In one region in which association was confirmed, fine‐mapping was performed (654 cases and 1,847 controls).

Results

Of the 112 SNPs that were significantly associated with JIA in the discovery cohort, 6 SNPs were associated with JIA in the independent validation cohort. The most strongly associated SNP mapped to the HLA region, while the second strongest association was with a SNP within the VTCN1 gene. Fine‐mapping of that gene was performed, and 10 SNPs were found to be associated with JIA.

Conclusion

This study is the first to successfully apply a SNP‐based genome‐wide association approach to the investigation of JIA. The replicated association with markers in the VTCN1 gene defined an additional susceptibility locus for JIA and implicates a novel pathway in the pathogenesis of this chronic disease of childhood.

     

Development and preliminary validation of a Children's Arthritis Self‐Efficacy Scale

Objective

To develop a valid and reliable measure of arthritis self‐efficacy for use with school‐age children with juvenile idiopathic arthritis (JIA).

Methods

Construction of the 11‐item Children's Arthritis Self‐Efficacy Scale (CASE) was based on an existing body of knowledge and the results of focus groups with children, their parents, and health professionals. Data for validation of the CASE were collected by self‐administered questionnaires completed by 89 children and 151 caregivers.

Results

Analyses revealed a 3‐factor structure relating to self‐efficacy for managing symptoms, emotional consequences, and activities, explaining 76.5% of the total variance. The CASE demonstrated high internal consistency, concurrent validity, and construct validity.

Conclusion

Preliminary findings suggest that the CASE is worthy of further psychometric testing and may have the potential to help delineate variations in adjustment among children with JIA.

     

Performance of a generic health‐related quality of life measure in a clinic population with rheumatic disease

Objective

To assess the performance of a generic health‐related quality of life (HRQOL) measure in a rheumatology clinic population.

Methods

Participants (n = 619) with fibromyalgia, rheumatoid arthritis, or osteoarthritis receiving care from rheumatologists completed mailed questionnaires that included the Behavioral Risk Factor Surveillance System (BRFSS) HRQOL measure and condition‐specific measures assessing disability, pain, fatigue, and helplessness. The BRFSS assesses global health and number of days in the past 30 of poor physical or mental health or activity limitation. The overall sample was described, followed by comparison of adjusted scores on all HRQOL measures by diagnosis.

Results

Participants reported mild difficulty with activities of daily living, marked pain and fatigue, and moderate helplessness. Participants reported a mean of 8 or more days out of 30 of poor physical and mental health and activity limitations; more than 40% reported poor or fair health. Participants with fibromyalgia reported more ill health on condition‐specific measures and the BRFSS HRQOL measures than did participants with osteoarthritis or rheumatoid arthritis.

Conclusion

The BRFSS HRQOL measure is a brief, easily administered, generic health indicator that shows differences among rheumatic disease diagnoses.

     

Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.

Methods

Synovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two‐dimensional gel electrophoresis for protein separation and matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry and quadripole time‐of‐flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA).

Results

The synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2‐fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA.

Conclusion

Despite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.

     

Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets

Objective

To determine whether peripheral blood mononuclear cells (PBMCs) from children with recent‐onset polyarticular juvenile idiopathic arthritis (JIA) exhibit biologically or clinically informative gene expression signatures.

Methods

Peripheral blood samples were obtained from 59 healthy children and 61 children with polyarticular JIA prior to treatment with second‐line medications, such as methotrexate or biologic agents. RNA was extracted from isolated mononuclear cells, fluorescence labeled, and hybridized to commercial gene expression microarrays (Affymetrix HG‐U133 Plus 2.0). Data were analyzed using analysis of variance at a 5% false discovery rate threshold after robust multichip analysis preprocessing and distance‐weighted discrimination normalization.

Results

Initial analysis revealed 873 probe sets for genes that were differentially expressed between polyarticular JIA patients and healthy controls. Hierarchical clustering of these probe sets distinguished 3 subgroups within the polyarticular JIA group. Prototypical patients within each subgroup were identified and used to define subgroup‐specific gene expression signatures. One of these signatures was associated with monocyte markers, another with transforming growth factor β–inducible genes, and a third with immediate early genes. Correlation of gene expression signatures with clinical and biologic features of JIA subgroups suggested relevance to aspects of disease activity and supported the division of polyarticular JIA into distinct subsets.

Conclusion

Gene expression signatures in PBMCs from patients with recent‐onset polyarticular JIA reflect discrete disease processes and offer a molecular classification of disease.

     

Evidence for linkage of HLA loci in juvenile idiopathic oligoarthritis: Independent effects of HLA–A and HLA–DRB1

Objective

Although multiple associations between HLA loci and juvenile oligoarthritis have previously been documented, evidence for linkage of HLA loci in oligoarthritis in UK Caucasians with juvenile idiopathic arthritis (JIA) has not been described. The aim of this study was to investigate linkage of HLA–A, B, and DRB1 in UK Caucasian JIA patients with oligoarthritis.

Methods

One hundred forty‐two families comprising affected offspring and their parents (45 with one parent available and 97 with both parents available) were typed for HLA–A, B, and DRB1 by polymerase chain reaction–sequence‐specific oligonucleotide probe. Single‐point and multipoint analyses were performed using various modifications of the extended transmission disequilibrium test. Linkage disequilibrium (LD) analysis was performed using the EH‐Plus system.

Results

Linkage to HLA–A and HLA–DRB1 was seen in oligoarthritis and in the International League of Associations for Rheumatology–defined subgroups of persistent oligoarthritis and extended oligoarthritis. Linkage to HLA–A, B, and DRB1 was also observed in female patients with oligoarthritis. Linkage of the HLA loci seemed to be attributable to maternal preferential transmission of alleles. Furthermore, LD patterns between the HLA–A, B, and DRB1 loci were investigated. HLA–A and HLA–DRB1 were confirmed as independent susceptibility loci for oligoarthritis.

Conclusion

This is the first study to establish linkage of HLA–A and HLA–DRB1 in oligoarthritis and to show that the 2 loci contribute independently to disease. Further studies are being performed to determine whether it is these loci or other genes in LD with them that are responsible for susceptibility to oligoarthritis in UK Caucasian patients with JIA.

     

Positive association of SLC26A2 gene polymorphisms with susceptibility to systemic‐onset juvenile idiopathic arthritis

Objective

To investigate SLC26A2, the gene that causes diastrophic dysplasia, in juvenile idiopathic arthritis (JIA).

Methods

Nine polymorphisms across the SLC26A2 gene locus were investigated using MassArray genotyping in 826 UK Caucasian JIA cases and 617 ethnically matched healthy controls.

Results

Significant associations between multiple single‐nucleotide polymorphisms (SNPs) across SLC26A2 and systemic‐onset JIA were found. In each case, homozygosity for the minor allele conferred the increased risk of disease susceptibility: rs1541915 (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 1.4–3.7, P = 0.0003), rs245056 (OR 2.8, 95% CI 1.7–4.6, P = 0.00002), rs245055 (OR 2.5, 95% CI 1.2–5.0, P = 0.004), rs245051 (OR 2.3, 95% CI 1.4–3.7, P = 0.0005), rs245076 (OR 2.7, 95% CI 1.3–5.4, P = 0.0015), and rs8073 (OR 2.3, 95% CI 0.9–5.6, P = 0.04).

Conclusion

These findings show the value of using monogenic disease loci as candidates for investigation in JIA. We identified a subgroup‐specific association between SNPs within the SLC26A2 gene and systemic‐onset JIA. Our findings also highlight systemic‐onset JIA as being a distinctly different disease from that in the other JIA subgroups.

     

Prevalence,risk factors,and outcome of uveitis in juvenile idiopathic arthritis: A long‐term followup study

Objective

To assess the prevalence, risk factors, and long‐term outcome of uveitis in patients with juvenile idiopathic arthritis (JIA).

Methods

An inception cohort of all 1,081 patients diagnosed as having JIA at a single tertiary care center was established. A questionnaire and followup telephone calls were used to confirm the diagnosis of uveitis. Ophthalmologists' records of patients with uveitis were collected. Kaplan‐Meier and Cox regression analyses were used to assess risk factors for developing uveitis and for complications of uveitis.

Results

After a mean followup time of 6.9 years, 142 of 1,081 patients (13.1%) had developed uveitis. Risk factors were young age at diagnosis, female sex, antinuclear antibody positivity, and the subtype of JIA. The relative contribution of these risk factors was different for the different subtypes of JIA. Until the end of the study, uveitis complications had developed in 53 of 142 patients with uveitis (37.3%; 4.9% of the total cohort). Only 16 of 175 involved eyes (9.1%) in 14 of 108 patients (13%; 1.3% of the total cohort) for whom ophthalmology reports were available had best corrected visual acuity less than 20/40 (mean followup time for uveitis of 6.3 years). Abnormal vision was associated with synechiae or cataract.

Conclusion

Risk factors for developing uveitis were different among subtypes of JIA. The long‐term outcome of JIA‐associated uveitis in our cohort was excellent despite the high rate of complications.

     

Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis

Objective

To explore biologic correlates to age at onset in patients with juvenile idiopathic arthritis (JIA) using peripheral blood mononuclear cell (PBMC) gene expression analysis.

Methods

PBMCs were isolated from 56 healthy controls and 104 patients with recent‐onset JIA (39 with persistent oligoarticular JIA, 45 with rheumatoid factor–negative polyarticular JIA, and 20 with systemic JIA). RNA was amplified and labeled using NuGEN Ovation, and gene expression was assessed with Affymetrix HG‐U133 Plus 2.0 GeneChips.

Results

A total of 832 probe sets revealed gene expression differences (false discovery rate 5%) in PBMCs from children with oligoarticular JIA whose disease began before age 6 years (early‐onset disease) compared with those whose disease began at or after age 6 years (late‐onset disease). In patients with early‐onset disease, there was greater expression of genes related to B cells and less expression of genes related to cells of the myeloid lineage. Support vector machine analyses identified samples from patients with early‐ or late‐onset oligoarticular JIA (with 97% accuracy) or from patients with early‐ or late‐onset polyarticular JIA (with 89% accuracy), but not from patients with systemic JIA or healthy controls. Principal components analysis showed that age at onset was the major classifier of samples from patients with oligoarticular JIA and patients with polyarticular JIA.

Conclusion

PBMC gene expression analysis reveals biologic differences between patients with early‐and late‐onset JIA, independent of classification based on the number of joints involved. These data suggest that age at onset may be an important parameter to consider in JIA classification. Furthermore, pathologic mechanisms may vary with age at onset, and understanding these processes may lead to improved treatment of JIA.

     

Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein‐Barr virus proteins in oligoarticular juvenile idiopathic arthritis

Objective

To evaluate whether abnormal T cell recognition may be generated by exposure to exogenous antigens presenting sequence homology with epitopes contained in self HLA alleles, and if such recognition may be part of the mechanisms that fuel inflammation in autoimmune diseases associated with certain HLA alleles.

Methods

Cytotoxic responses of peripheral blood mononuclear cells to 9‐mer peptides derived from HLA molecules (DRB1*1101, DRB1*0801, or DPB1*0201) associated with oligoarticular juvenile idiopathic arthritis (JIA) or homologous peptides derived from Epstein‐Barr virus (EBV) proteins (Bolf1 or Balf2) were analyzed in patients with oligoarticular JIA and in healthy controls matched for HLA–DRB1*1101, DRB1*0801, or DPB1*0201. Production of proinflammatory cytokines in culture supernatants was determined by enzyme‐linked immunosorbent assay.

Results

T cell cytotoxic responses and production of proinflammatory cytokines in response to stimulation with self HLA–derived peptides were found only in patients with oligoarticular JIA, and not in controls. Patients with oligoarticular JIA, but none of the healthy controls, had EBV–self HLA cross‐reactive T cells.

Conclusion

Our data suggest a disease‐ and allele‐specific mechanism of autoimmunity in oligoarticular JIA. This mechanism may be part of the pathogenesis of the disease, and could be the basis of one of the likely multiple candidates for antigen‐specific immunotherapy approaches in the future.

     

Ongoing disease activity and changing categories in a long‐term nordic cohort study of juvenile idiopathic arthritis

Objective

To describe the disease characteristics, long‐term course, and outcome of patients with juvenile idiopathic arthritis (JIA) in a population‐based setting.

Methods

Consecutive cases of JIA from defined geographic areas of Denmark, Finland, Sweden, and Norway in whom disease onset occurred in 1997–2000 were included in a prospective, multicenter cohort study. The study was designed to be as close to a population‐based study as possible, with centers participating only if they were able to include in their catchment area all children in whom JIA was diagnosed.

Results

Of 500 children included, 440 (88.0%) had repeated visits, with the last visit occurring at least 7 years after disease onset (median 98 months, range 84–147 months). Changes in the International League of Associations for Rheumatology category were observed in 10.8% of the children, and, in addition, extended oligoarthritis developed in 34.7% of the group with oligoarticular JIA. During the observation period, 58.0% of the children were treated with disease‐modifying antirheumatic drugs, including biologic medications. Ongoing disease activity was mostly mild, but some JIA‐related damage developed in 22.9% of the children. At the last followup visit, remission off medication was observed in 42.4% of the children, 8.9% were in remission on medication, and 48.7% were not in remission. The highest rates of remission were observed in patients with persistent oligoarticular JIA and in those with systemic JIA.

Conclusion

In this long‐term prospective study of JIA in a population‐based Nordic setting, ongoing disease was evident in a majority of the children. The present results underline the need to identify early predictors of outcome, to further improve therapy, and to continue long‐term followup of patients with JIA.