Soluble interleukin-2 receptor serum levels facilitate prediction of relapses in subgroups of patients with juvenile idiopathic arthritis.

OBJECTIVES: JIA is characterised by a chronic disease course. Once patients achieve a state of inactive disease, there are no established biomarkers to predict the further course of inflammation for these patients. Therefore, the purpose of this study was to quantify serum biomarkers during quiescent disease to evaluate their use in identifying JIA patients at risk for future disease flare. METHODS: Patients with non-systemic JIA reaching inactive disease status were divided into two groups: 92 patients with future active disease after a median period of 6 months (range 3-9) and 80 patients with persistent inactive disease for the following period (median 11 months, range 7-16) according to the juvenile arthritis DAS (JADAS). Clinical parameters and serum levels of various biomarkers were measured in the state of inactive disease using immunoassays in both groups and were analysed for their potential to predict the further course of disease. RESULTS: Soluble interleukin-2 receptor (sIL-2R) serum levels were significantly higher in patients with future active disease (P = 0.021), which especially applied to patients with RF-negative polyarticular and extended oligoarticular JIA (P < 0.001). Higher sIL-2R serum levels during inactive disease were associated with a greater number of active joints at future active disease. CONCLUSION: Patients without clinical signs of disease activity already presented with increased sIL-2R serum levels several months before disease relapses, whereas conventional inflammation parameters were not elevated. Determination of sIL-2R serum levels during inactive disease may facilitate identifying patients with subclinical disease activity at risk for future active disease.

Myositis-specific autoantibodies and their associated phenotypes in juvenile dermatomyositis: data from a German cohort.

OBJECTIVES: To describe a German cohort of patients with juvenile dermatomyositis (JDM) and to evaluate clinical manifestations, disease course and prognosis in JDM patients with a certain myositis-specific autoantibody. METHODS: Cross-sectional data on patients with JDM documented in the National Paediatric Rheumatologic Database in Germany between 2014 and 2016 were analysed. In a subgroup of the cohort, MSAs were determined with a commercial multiplex array, and a retrospective chart review was conducted to specify the clinical phenotype and patient outcome. RESULTS: The total cohort consisted of 196 patients with JDM (mean age 12.2±4.0 years, mean disease duration 5.1±3.8 years, 70% female). Apart from typical skin changes and muscle weakness, 41% of patients also had arthritis and/or contractures, 27% had calcinosis and approximately 10% had interstitial lung disease. Immunoblot testing was performed on the sera of 91 (46%) patients, detecting MSAs in 44% of patients. Patient groups with specific MSAs differed in clinical characteristics such as calcinosis, dysphagia, and lung and joint involvement. The extent of muscle weakness evaluated by the Childhood Myositis Assessment Scale was significantly associated with an increased level of creatine kinase. Patients with anti-MDA5 were particularly affected by polyarthritis of the small joints. After 5 years, 51 patients of the MSA cohort (56.0%) achieved an inactive disease state, 12/51 (23.5%) were off therapy. CONCLUSIONS: Patients with JDM in Germany show a broad spectrum of clinical manifestations that can be grouped into homogeneous groups using MSA, which also helps to predict the course and prognosis of the disease.

Consumer perspective on healthcare services for juvenile idiopathic arthritis: results of a multicentre JIA inception cohort study.

OBJECTIVES: To evaluate healthcare services for patients with juvenile idiopathic arthritis (JIA) from the parent-proxy perspective and to identify factors associated with perceived deficits in care. METHODS: Patients with JIA from 11 paediatric rheumatology units were enrolled in an inception cohort within the first 12 months after diagnosis. Healthcare services were assessed using The Child Healthcare Questionnaire on satisfaction, utilisation and needs. Factors associated with deficits in care were identified by logistic regression analysis. RESULTS: Data from parents of 835 JIA-patients were included in the analysis. At the assessment (4.7 months after diagnosis), 85% of the patients received drug treatment, and 50% had received multi-professional care. The most frequently used services were physiotherapy (84%), occupational therapy (23%), and telephone counselling (17%). Almost one-third of families reported that they had not received the services that they needed, with health education being the most frequently reported need. Most parents (93%) were satisfied with the overall healthcare provided for their children, especially regarding doctors' behaviour. However, approximately 1 in 3 consumers were dissatisfied with the time to JIA diagnosis and the school services. The lower the child's quality of life, the higher the chance was that the child and the family received multi-professional care, perceived unmet needs, and were dissatisfied with care. CONCLUSIONS: According to parents' experience and satisfaction with their child's care, performance at the system level can be further improved by diagnosing JIA earlier, providing additional information at disease onset, and ensuring that the child's social environment is taken into account.

Pregnancy outcomes in DMARD-exposed patients with juvenile idiopathic arthritis-results from a JIA biologic registry.

OBJECTIVES: To investigate the courses and outcomes of pregnancies involving JIA patients who were exposed to DMARDs. METHODS: In the Juvenile arthritis MTX/Biologics long-term Observation study, pregnant patients or male patients with pregnant partners were identified. Standardized patient interviews were conducted, and the course and outcome of pregnancy were assessed. Prospectively collected physician- and patient-reported data were also considered in the analysis. RESULTS: The study sample included 152 pregnancies in 98 women with JIA and 39 pregnancies involving 21 male patients as partners. The majority of patients had polyarticular-onset/-course JIA (61%). The average age of patients at first pregnancy was 24.1 (4.5) years, and their mean disease duration was 13.8 (5.9) years. Patients had been exposed to DMARDs for 9.5 (5.6) years, and 90% of these patients had received biologics before. Half of the pregnancies occurred during DMARD exposure, mostly with etanercept. Significant differences in pregnancy outcomes between DMARD-exposed and -unexposed pregnancies were not observed. Spontaneous abortion (13.1%) and congenital anomaly (3.6%) rates were not suggestive of increased risk compared with expected background rates. However, the rates of premature birth (12.3%) and caesarean section (37.7%) were slightly above those in the German birthing population. The disease activity of female patients remained relatively stable in pregnancy, with mean cJADAS-10 scores of 5.3, 7.1 and 5.6 in each trimester, respectively. CONCLUSION: Young adults with JIA often become pregnant or become fathers of children while still being treated with DMARDs. Data suggest no increased risk of major adverse pregnancy outcomes.

Adherence to ophthalmological screening recommendations and course of uveitis in children with juvenile idiopathic arthritis: data from the Inception Cohort of Newly diagnosed patients with JIA (ICON-JIA) study.

OBJECTIVES: As JIA-associated uveitis (JIAU) is asymptomatic in the majority of patients, ophthalmologic screening examinations are recommended, depending on the risk constellation for uveitis development. This study analyses disease characteristics in JIAU depending on adherence with the screening intervals. METHODS: 953 patients were included in the ICON registry. In patients without uveitis, ophthalmologic screening was recommended in accordance with the standards currently applied in Germany. Dates and results of the screening examinations were noted for each patient. RESULTS: Until the 3-year-follow up, uveitis developed in 133 of 953 JIA patients. In 56 of them, uveitis was present before study inclusion, and those were excluded from the prospective analysis. For the remaining 897 JIA patients, screening results were available in 557, 46 of whom developed uveitis. In those patients, adherence with the suggested screening intervals until uveitis onset was assessed, and patients were classified accordingly: screenings as recommended (Sc+ group, n=356) vs. infrequent screening (Sc- group, n=201). Non-adherence with the screening schedule significantly correlated with younger age at study inclusion and JIA diagnosis, shorter JIA disease duration, JIA oligoarthritis subtype and positive antinuclear antibody status. The Sc+ group had a better visual acuity (VA) at initial uveitis diagnosis, however, at the 3-year-follow up, VA and uveitis complication rates did not differ significantly. CONCLUSIONS: Especially high-risk patients often do not adhere to the initial frequently recommended screening intervals, resulting in a reduced visual acuity at initial uveitis diagnosis. A recommendation for changing the current screening intervals cannot be deduced from our data.

[Rheumatic diseases in childhood and adolescence: importance of early multi-professional care]. / Rheumatische Erkrankungen im Kindes- und Jugendalter: Wichtigkeit einer frühzeitigen multiprofessionellen Versorgung.

Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children. Both the disease, which is accompanied by pain and movement restrictions, and its usually complex, long-term therapy, are associated with burdens for those affected until adulthood. Impairments can affect many areas of life. Holistic care that considers the preferences and expressed needs of patients and their families is crucial in order to achieve the desired therapeutic goals of remission and the best possible quality of life. Since JIA begins in a very early phase of life, long-term consequences due to illness and therapy are of considerable importance.The approval of new substances that specifically intervene in the inflammatory process has fundamentally changed the treatment of JIA in recent years. Above all, early effective therapy makes a decisive contribution to an improved prognosis of JIA patients. Meanwhile, JIA patients enter adulthood with good everyday function and quality of life as well as less secondary damage and concomitant diseases, although only about half achieve stable therapy-free remission. In order to support the necessary transition into adult medicine, transition programmes have been developed to prepare young rheumatics for the new form of care and to prevent gaps in care and unfavourable outcomes. Last but not least, the recording of psychological factors is important in order to support the chronically ill in dealing with their illness and the resulting challenges, if necessary.

Predictive factors and biomarkers for the 2-year outcome of uveitis in juvenile idiopathic arthritis: data from the Inception Cohort of Newly diagnosed patients with Juvenile Idiopathic Arthritis (ICON-JIA) study.

OBJECTIVE: To define predictors for the 2-year outcome in terms of achieving inactivity, subsequent uveitis reactivation and occurrence of uveitis-related complications of JIA-associated uveitis. METHODS: Demographic and clinical parameters and serum samples of JIA-associated uveitis patients enrolled in ICON at ⩽1 year of JIA diagnosis were collected at study enrolment, every 3 months during the first year and subsequently every 6 months. Predictors for the 2-year outcome were evaluated by linear mixed models. RESULTS: Of 954 JIA patients included, uveitis occurred in 106 up to the first 2-year follow-up, with 98 of them having complete ophthalmological documentation. In 81.8% and 80.0% of patients, uveitis inactivity was achieved at the 1- and 2-year follow-up after uveitis onset, respectively. JIA onset after the age of 5 years, no use of topical corticosteroids, and adalimumab treatment were significantly associated with an inactive uveitis for at least 6 months (n = 57). Correlates for subsequent uveitis reactivation (n = 16, 30.2%) were age at uveitis onset ⩽5 years and active disease (clinical Juvenile Arthritis Disease Activity Score >4.5). Uveitis-related complications were present in 29.8% of patients at first uveitis documentation and in 30.7% and 32.8% at 1- and 2-year follow-up, respectively. Older age at JIA onset, short duration between JIA and uveitis onset, high anterior chamber (AC) cell grades, poor visual acuity, and topical steroid use at first uveitis documentation correlated with uveitis-related complications. CONCLUSION: In addition to demographic risk factors, JIA disease and uveitis activity scores and adalimumab are significant predictors for the 2-year outcome of JIA-associated uveitis patients.

Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA.

OBJECTIVES: To determine the reasons of methotrexate (MTX) discontinuation, frequency of adverse events (AE) and whether the time in inactive disease before MTX withdrawal disease is associated with the risk of disease flare. METHODS: Patients with juvenile idiopathic arthritis (JIA) beginning treatment with MTX were prospectively observed in the national JIA biologic register Biologika in der Kinderrheumatologie/Biologics in Paediatric Rheumatology and its follow-up register Juvenile arthritis Methotrexate/Biologics long-term Observation. Inactive disease was defined by a clinical Juvenile Arthritis Disease Activity Score ≤1, flare after MTX discontinuation by reoccurrence of at least moderate disease activity or restart of treatment with a disease-modifying antirheumatic drug . RESULTS: MTX treatment was initiated in 1514 patients after a mean disease duration of 2.1 years (SD=2.8). 40% of the patients experienced oligoarticular onset of JIA. MTX was discontinued in 982 (64.9%) patients. Ineffectiveness (36.9%) and achieving inactive disease (32.1%) were the most common reasons. Among the latter (n=316), 184 (58.2%) patients experienced a flare on follow-up. The likelihood of a flare was a function of time in inactive disease prior to MTX discontinuation (HR 0.95; 95% CI 0.92 to 0.97). Patients with inactive disease for longer than 12 months had a significantly lower flare rate (58 of 119, 48.7%; HR 0.48; 95% CI 0.34 to 0.69). The most frequently reported AE was MTX intolerance, including nausea, aversion and vomiting, accounting for 441 events (13.0 events/100 exposure years) in 307 (20.3%) patients. CONCLUSIONS: Patients who spent at least 12 months in inactive disease before MTX discontinuation had a significantly lower flare rate.

Comorbidity of Type 1 Diabetes Mellitus in Patients with Juvenile Idiopathic Arthritis.

OBJECTIVES: To determine the prevalence of type 1 diabetes mellitus (T1D) in patients with juvenile idiopathic arthritis (JIA) and to characterize patients having both. STUDY DESIGN: Diabetes comorbidity was recorded in the National Pediatric Rheumatologic Database since 2012. Data from the North Rhine-Westphalian diabetes registry served as the reference population for the prevalence of diabetes in the general population. The National Pediatric Rheumatologic Database data were indirectly standardized for age and sex for comparison with the general population. The diabetes prevalence ratio was calculated using the Poisson regression model. RESULTS: The analysis included 12 269 patients with JIA. A total of 58 patients had comorbid T1D, and the diabetes prevalence was 0.5%. The mean age was 11.6 years at the time of documentation, and the mean disease duration was 4.2 years. Compared with the general population, the prevalence of diabetes in patients with JIA was significantly increased (prevalence ratio 1.76 [95% CI 1.34; 2.28], P < .001). The onset of diabetes in patients with JIA was earlier than that reported in the reference data. Sixty-three percent of patients developed T1D before JIA. On average, diabetes onset was 56 months before the onset of JIA. Patients who first developed JIA developed T1D on average 40 months later. The majority of patients had not received disease-modifying antirheumatic drugs before diabetes onset. CONCLUSIONS: T1D occurs more frequently in patients with JIA than in the general population. The likelihood of T1D occurrence appears to be slightly higher before JIA manifestation and without disease-modifying antirheumatic drug therapy after JIA onset.

Long-term safety of etanercept and adalimumab compared to methotrexate in patients with juvenile idiopathic arthritis (JIA).

IMPORTANCE: Published evidence on the long-term safety of etanercept (ETA) and adalimumab (ADA) in patients with polyarticular juvenile idiopathic arthritis (pJIA) is still limited. OBJECTIVES: To investigate the rates of serious adverse events (SAE) and of events of special interest (ESI) under ETA and ADA treatment. DESIGN, SETTING AND PARTICIPANTS: Patients with pJIA were prospectively observed in the national JIA biological register, Biologika in der Kinderrheumatologie, and its follow-up register, Juvenile arthritis Methotrexate/Biologics long-term Observation. MAIN OUTCOMES AND MEASURES: We calculated the relative risks of SAE and ESI for ETA and ADA compared with methotrexate (MTX). RESULTS: Among the 1414 patients treated with ETA (n=1414; 4461 exposure years (EY)) and ADA (n=320; 493 EY), significantly more SAE, infections and medically important infections were observed (ETA: 4.5, 5.7, 0.9; ADA: 4.7, 11.4, 0.4 per 100 EY) compared with those treated with MTX alone (n=1455; 2.907 EY; 2.6, 5.5, 0.5 per 100 EY). The risk for malignancies was not significantly increased for ETA and ADA compared with MTX (0.09, 0.27 and 0.07/100 person-years). Patients under ETA monotherapy developed more frequently incident inflammatory bowel disease (IBD) and incident uveitis (0.5 and 0.8/100 EY) than patients treated by ETA in combination with MTX (0.1 and 0.2/100 EY) or MTX alone (0.03 and 0.1/100 EY). CONCLUSIONS AND RELEVANCE: Our data confirm the acceptable long-term tolerability of ETA and ADA in pJIA. However, whether the onset of IBD and uveitis during ETA monotherapy is a paradoxical effect or an inadequate response to therapy remains unclear and requires further investigation in this growing cohort.

Risk perception, well-being, depression and anxiety in children and adolescents with rheumatic diseases during the COVID-19 pandemic - results from the prospective multicenter KICK-COVID study in Germany.

OBJECTIVE: To investigate the psychosocial burden in children and adolescents with juvenile rheumatic diseases during the COVID-19 pandemic. METHODS: As part of the multicentre observational KICK-COVID study linked to the National Pediatric Rheumatology Database, adolescents < 21 years and parents of children < 12 years with rheumatic diseases answered questions on perceptions of health risk (PHR) due to SARS-CoV2, stress, well-being (WHO-5) and symptoms of depression (PHQ-9) and anxiety (GAD-7). Data were collected at routine visits from June to December 2021 and assessed for association with demographic and clinical parameters, treatment and patient-reported outcomes by multivariable regression analyses. RESULTS: Data from 1356 individuals (69% female, 50% adolescents) were included. Median PHR on a numeric rating scale (NRS, 0-10) was 4 (IQR 2-6), median perceived stress was 3 (IQR 1-6). Adolescents reported a worse well-being with a significantly lower median WHO-5-score (60, IQR 40-76) than parents reported for their children < 12 years (80, IQR 68-84). Moderate to severe symptoms of depression and anxiety were reported by 14.3% and 12.3% of the adolescents, respectively. PHR was significantly higher in patients with systemic lupus erythematosus, methotrexate or biologic disease-modifying anti-rheumatic drug therapy than in patients without these characteristics, whereas lower WHO-5 or higher PHQ-9 or GAD-7 scores were only associated with poorer patient-reported health status and physical functioning. CONCLUSION: The perception of health risk due to SARS-CoV2 infection was not paralleled by an impairment of mental health, which were, however, significantly correlated with self-rated health status and functional capacity, highlighting the importance of patient-reported outcome assessment. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), no. DRKS00027974. Registered on 27th of January 2022.

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study.

BACKGROUND: Physical active lifestyles are essential throughout growth and maturation and may offer potential preventive and therapeutic benefit in patients with juvenile idiopathic arthritis (JIA). Insufficient physical activity (PA), in contrast, can lead to aggravation of disease-related symptoms. This study aimed to i) examine PA levels in children and adolescents with JIA compared to general population controls and ii) investigate correlates of pronounced physical inactivity in order to identify risk groups for sedentary behaviour. METHODS: Data from children and adolescents with JIA and population controls aged 3 to 17 years documented in the National Pediatric Rheumatologic Database (NPRD) and the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were used. Self-reported PA was collected from parents/guardians of children up to 11 years of age or adolescents 12 years of age and older. To compare PA-related data, age- and sex-specific pairwise analyses were conducted considering NPRD/KiGGS participants' data from 2017. Correlates of physical inactivity among patients were identified using a linear regression model. RESULTS: Data of 6,297 matched-pairs (mean age 11.2 ± 4.2 years, female 67%, patients' disease duration 4.5 ± 3.7 years, persistent oligoarthritis 43%) were available for evaluation. Almost 36% of patients aged 3-17 years (vs. 20% of controls) achieved the WHO recommended amount of PA, while PA steadily decreased with age (18% of patients aged ≥ 12 years) and varied between JIA categories. Female adolescents and patients with enthesitis-related arthritis were least likely to achieve the minimum recommended level of PA. Physical inactivity was associated with female sex, higher age at disease onset, longer disease duration, more functional disability (C-HAQ) and higher disease activity (cJADAS-10). CONCLUSIONS: Depending on JIA category, children and adolescents with JIA were similarly or even more likely to achieve the WHO recommended minimum level of PA compared to general population controls. However, since a large proportion of young JIA patients appear to be insufficiently physically active, engagement in targeted efforts to promote PA is urgently needed.

Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening.

BACKGROUND: Previous studies have shown that growing up with rheumatic conditions can fuel dissatisfaction and psychological distress, which in turn affects disease self-management and treatment adherence. Primary objective of this study was to estimate the prevalence of anxiety and depression symptoms in adolescents and young adults (AYA) with juvenile idiopathic arthritis (JIA) and to identify correlates of conspicuous screening results. METHODS: Initiated as part of the COACH multicenter observational study, outpatients aged 12 to 21 years participating in the National Pediatric Rheumatological Database (NPRD) were prospectively screened for mental health using the Patient Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder Scale-7 (GAD-7). RESULTS: Data from 1,150 adolescents with JIA (mean age 15.6 ± 2.2 years; mean disease duration 7.2 ± 4.9 years, 69% female, 43% oligoarthritis, 26% polyarthritis) were analysed. Overall, 32.7% (n = 316) of AYA showed conspicuous screening results, of whom 30.4% reported clinically relevant suicidal or self-harm thoughts. About 19% of screened patients showed moderate to severe depressive or anxious symptoms. AYA with conspicuous screening results were older (15.8 vs. 15.2 years; p < 0.0001), more often female (81% vs. 64%; p < 0.0001) and more often overweight (25% vs. 17%; p = 0.006). They had higher disease activity (physician global assessment on NRS 0-10; 1.7 vs. 1.2; p < 0.0001), more functional limitations (CHAQ; 0.44 vs. 0.14; <0.0001) and rated their health status worse (NRS 0-10; 3.5 vs. 1.8; p < 0.0001) than AYA with inconspicuous screening results. Females (OR 2.33 [CI 1.53-3.56]; p < 0.0001), older age (OR 1.09 [CI 1.01-1.18]; p = 0.026), patients with more functional limitations (OR 3.36 [CI 1.98-5.72]; p < 0.0001), and patients with worse subjective health status (OR 1.17 [CI 1.07-1.27]; p < 0.0001) were more likely to have a conspicuous screening result. Regular sports participation was associated with a lower likelihood of conspicuous screening result (OR 0.69 [CI 0.49-0.98]; p = 0.039). CONCLUSIONS: A large-scale outpatient screening of AYA with JIA in Germany shows a high prevalence of anxiety and depression symptoms. The need for routine screening for early detection of mental health problems became apparent.

Comorbidity profiles among adult patients with juvenile idiopathic arthritis: results of a biologic register.

OBJECTIVES: This study aims to assess the prevalence of comorbidities in adult JIA and the impact of comorbidity on patients' perceived health state. METHODS: Self-reported comorbidity was studied in 344 adult JIA patients who have been included in the biologic register JuMBO. The comorbidity prevalence among the patients was compared to an age- and sex-matched reference group from the population. The correlation of comorbidity with clinical and demographic parameters was analysed by linear or logistic regression models. RESULTS: Sixty two percent of the JIA patients reported at least one comorbidity. Uveitis was the most common comorbid condition (17.7%), followed by allergic rhinitis (14.5%), migraine (8.7%), and atopic dermatitis (8.7%). The prevalence of cardiovascular disorders was 9.9%, which was not higher than that in the population. However, patients with a systemic onset of JIA (soJIA) had a substantially higher rate of cardiovascular diseases of 40.6% (p=0.033). Patients with soJIA also had the highest prevalence (80.0%) and the highest mean number (1.8) of comorbidities. Patients with at least one comorbid condition suffered more often from fatigue and pain, had a lower functional capacity (p<0.001, each), and a lower physical and mental health-related quality of life than those without comorbidities (p<0.001 and p=0.017, respectively). The presence of any comorbidity and the level of disease activity were independent predictors of a lower SF-36 score. CONCLUSIONS: Our results indicate that comorbid conditions have a significant impact on the perceived health state in adult JIA. Among all JIA patients, those with systemic onset carry the highest risk for comorbidities, in particular for cardiovascular disorders.

Long-term follow-up of children with chronic non-bacterial osteomyelitis-assessment of disease activity, risk factors, and outcome.

INTRODUCTION: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO. OBJECTIVE: To assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors. METHODS: From 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years. RESULTS: Four hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p < 0.001; mean MRI lesions 0.9 (p < 0.001)) was documented. A significant improvement of physician global disease activity (PGDA), patient-reported overall well-being, and childhood health assessment questionnaire (C-HAQ) was documented. Therapeutically, an increase of disease-modifying anti-rheumatic drugs over the years can be stated, while bisphosphonates rather seem to be considered as a therapeutic DMARD option in the first years of disease. Only 5-7% of the patients had a severe disease course as defined by a PGDA > = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU. CONCLUSION: An improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.

Adherence, helpfulness and barriers to treatment in juvenile idiopathic arthritis - data from a German Inception cohort.

OBJECTIVES: To develop and evaluate German versions of the Parent Adherence Report Questionnaire (PARQ) and Child Adherence Report Questionnaire (CARQ) and to evaluate adherence in patients with juvenile idiopathic arthritis (JIA). METHODS: The PARQ and CARQ were translated into German, cross-culturally adapted and administered to patients (age ≥ 8 years) and their parents enrolled in the Inception Cohort Study of newly diagnosed JIA patients (ICON). The psychometric issues were explored by analyzing their test-retest reliability and construct validity. RESULTS: Four hundred eighty-one parents and their children with JIA (n = 465) completed the PARQ and CARQ at the 4-year follow-up. Mean age and disease duration of patients were 10.1 ± 3.7 and 4.7 ± 0.8 years, respectively. The rate of missing values for PARQ/CARQ was generally satisfactory, test-retesting showed sufficient reliability. PARQ/CARQ mean child ability total scores (0-100, 100 = best) for medication were 73.1 ± 23.3/76.5 ± 24.2, for exercise: 85.6 ± 16.5/90.3 ± 15.0, for splints: 72.9 ± 24.2/82.9 ± 16.5. Construct validity was supported by PARQ and CARQ scores for medications, exercise and splints showing a fair to good correlation with the Global Adherence Assessment (GAA) and selected PedsQL scales. Adolescents showed poorer adherence than children. About one third of the parents and children reported medication errors. Perceived helpfulness was highest for medication, and adverse effects were reported the greatest barrier to treatment adherence. CONCLUSIONS: The German versions of the PARQ and CARQ appear to have a good reliability and sufficient construct validity. These questionnaires are valuable tools for measuring treatment adherence, identifying potential barriers and evaluating helpfulness of treatments in patients with JIA.

Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO.

OBJECTIVE: To assess the outcome of adult patients with JIA who received etanercept (ETA) during childhood. METHODS: JuMBO (Juvenile arthritis MTX/Biologics long-term Observation) is an ongoing prospective cohort study. It follows adult JIA patients who were formerly included in the national JIA biologic register. In JuMBO, clinical status, therapy and the occurrence of adverse events are documented every 6 months by physicians; additionally, patient-derived data are included [e.g. functional capacity and health-related quality of life (HRQoL)]. Here, data from the last available visit of patients were analysed. RESULTS: Until December 2010, 346 patients with a median age of 21 years were included in JuMBO. The majority of them had polyarthritis. Seventy-eight per cent of them were still on DMARDs, 45% on ETA. The disease was inactive in about one in five patients. A restricted functional capacity was reported by 51% of participants and fatigue by 76%. The patients judged their HRQoL to be lower than a reference group from the general population, but only with regard to physical health. HRQoL correlated with the patient's perceived fatigue. Most frequently observed comorbidities in the young adults with JIA were disease related and included uveitis, IBDs and psoriasis. During the observation period, 2.1 severe infections and 1.5 new-onset autoimmune events per 100 patient-years were reported in patients on ETA, respectively. CONCLUSION: The first data from the JuMBO register indicate an improved long-term outcome of patients with severe JIA treated in the biologic era and an acceptable safety profile of ETA.

Occurrence and Risk Factors of Uveitis in Juvenile Psoriatic Arthritis: Data From a Population-based Nationwide Study in Germany.

OBJECTIVE: Data on uveitis in juvenile psoriatic arthritis (JPsA), a category of juvenile idiopathic arthritis (JIA), are scarce. We describe prevalence and risk factors for JPsA-associated uveitis (JPsA-U). METHODS: Cross-sectional data from the German National Pediatric Rheumatological Database (2002-2014) were used to characterize JPsA-U and assess risk factors for the development of uveitis. RESULTS: Uveitis developed in 6.6% of 1862 patients with JPsA. Patients with JPsA-U were more frequently female (73.0 vs 62.9%, P = 0.03), antinuclear antibody (ANA) positive (60.3 vs 37.0%, P < 0.001), younger at JPsA onset (5.3 ± 4.1 vs 9.3 ± 4.4 yrs, P < 0.001), and treated with disease-modifying antirheumatic drugs (DMARDs) significantly more frequently compared with JPsA patients without uveitis. On a multivariable analysis of a subgroup of 655 patients enrolled in the study ≤ 1 year after arthritis onset, mean clinical Juvenile Arthritis Disease Activity Score for 10 joints during study documentation was significantly associated with uveitis development. Children with early onset of JPsA (aged < 5 yrs vs ≥ 5 yrs) were significantly more frequently ANA positive (48.4% vs 35.7%, P < 0.001), affected by uveitis (17.3% vs 3.8%, P < 0.001), and treated with DMARDs (52.9% vs 43.8%, P < 0.001), but less often affected by skin disease (55.3% vs 61.0%, P = 0.03). CONCLUSION: The characteristics of patients with JPsA developing uveitis are similar to those of patients with uveitis in other JIA categories, such as oligoarticular JIA. Children with early-onset JPsA are at a higher risk for ocular involvement. Our data support the notion of a major clinical difference between those patients with early vs late onset of JPsA.

Prevalence of autoantibodies in patients with juvenile idiopathic arthritis: results from the German inception cohort ICON-JIA.

BACKGROUND: An association of different autoimmune diseases is suspected. In juvenile idiopathic arthritis (JIA), only few and partially conflicting data on the co-existence of other autoimmune disorders are available. The prevalence of autoantibodies in patients with JIA in Germany is not known. METHODS: Samples from 499 patients (median age at time of blood collection 11 years, median disease duration 4.4 years) in the prospective, multicenter inception cohort of children newly diagnosed with JIA (ICON-JIA) were analysed for the presence of anti-thyroid antibodies, celiac disease-specific antibodies (anti-tTG IgA, anti-tTG IgG), and connective tissue disease-associated antibodies (CTD-screen). RESULTS: A total of 76 (15.2%) patients had either clinically diagnosed autoimmune comorbidity or elevated autoantibodies. Of 21 patients with clinical autoimmune comorbidity, only 8 were also serologically positive at the time of testing, while 55 patients had autoantibodies without clinical diagnosis. Thus, 63 patients (12.6%) had at least one elevated autoantibody. Antibodies against thyroglobulin were found in 3% and against thyreoperoxidase in 4% of the samples. TSH receptor antibodies could not be detected in any of the 499 patients. Tissue transglutaminase antibodies were elevated in 0.4% of the patients. A positive screen for CTD-specific antinuclear antibodies was found in 7%, but only rarely specific antibodies (anti-dsDNA 1.4%, anti-SS-A and -SS-B 0.2% each, anti-CENP-B 0.4%) were confirmed. CONCLUSIONS: In our study, a specific correlation between JIA and other autoimmune phenomena could not be confirmed. The lack of well-matched control groups makes interpretation challenging. Further data need to corroborate the suspected increased risk of developing other autoimmune phenomena in JIA patients.

Medication burden in young adults with juvenile idiopathic arthritis: data from a multicentre observational study.

OBJECTIVE: To assess the medication and disease burden of young adults with juvenile idiopathic arthritis (JIA). METHODS: Young adults with JIA prospectively followed in the Juvenile Arthritis Methotrexate/Biologics long-term Observation reported on their health status and medication use. All medications taken (disease-modifying antirheumatic drugs (DMARDs)/prescription/over-the-counter drugs, but excluding most local therapies) classified according to the Anatomical Therapeutic Chemical Classification System were included in this analysis. Medication use at last follow-up was evaluated by sex, JIA category and time from symptom onset to the first biological DMARD (bDMARD) start. RESULTS: A total of 1306 young adults (68% female) with JIA and a mean disease duration of 13.6±6 years were included in the study. Patients reported using on average 2.4±2.1 medicines and 1.5±1.7 non-DMARD medicines, respectively, at the last follow-up. Almost a quarter of the patients reported polypharmacy. The higher the number of medications used was, the higher the disease activity, pain and fatigue, and the lower the quality of life of patients. Medication usage differed significantly between sexes and JIA categories, being highest in patients with rheumatoid factor-positive polyarthritis and systemic JIA. The number of medications used was significantly associated with the time from symptom onset to bDMARD start. Patients taking opioids or antidepressants had a particularly high disease burden and had received bDMARDs an average of 2 years later than patients not taking these medications. CONCLUSION: Medication use in adults with JIA varies depending on sex, JIA category, and the time between symptom onset and initiation of treatment with bDMARD.