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Juvenile idiopathic arthritis (JIA) is the most common systemic disease causing uveitis in childhood, with a prevalence of 10 per 100 000 persons. JIA often takes a severe inflammatory course, and its complications often endanger vision.This review is based on pertinent articles retrieved by a selective literature search up to 18 August 2014 and on the current interdisciplinary S2k guideline on the diagnostic evaluation and anti-inflammatory treatment of juvenile idiopathic uveitis.Uveitis arises in roughly 1 in 10 patients with JIA. Regular eye check-ups should be performed starting as soon as JIA is diagnosed. 75-80% of patients are girls; antinuclear antibodies are found in 70-90%. The risk to vision is higher if JIA begins in the preschool years. As for treatment, only a single, small-scale randomized controlled trial (RCT) and a small number of prospective trials have been published to date. Topical corticosteroids should be given as the initial treatment. Systemic immunosuppression is needed if irritation persists despite topical corticosteroids, if new complications arise, or if the topical steroids have to be given in excessively high doses or have unacceptable side effects. If the therapeutic effect remains inadequate, conventional and biological immune modulators can be given as add-on (escalation) therapy. Treatment lowers the risk of uveitis and its complications and thereby improves the prognosis for good visual function.Severely affected patients should be treated in competence centers to optimize their long-term outcome. Multidisciplinary, individualized treatment is needed because of the chronic course of active inflammation and the ensuing high risk of complications that can endanger vision. Future improvements in therapy will be aided by prospective, population-based registries and by basic research on biomarkers for the prediction of disease onset, prognosis, tissue damage, and therapeutic response.

To evaluate the efficacy and safety of etanercept in patients with enthesitis-related arthritis (ERA) in juvenile idiopathic arthritis (JIA).This was a 2-phase study in JIA patients with active, refractory ERA. Phase I was an open-label, uncontrolled 24-week study period in which all patients were administered etanercept. Patients considered to be treatment responders at week 24 according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) criteria for improvement in juvenile arthritis entered the second phase, a 24-week randomized, double-blind, placebo-controlled withdrawal study, for an additional 24 weeks, for evaluation of the primary end point, occurrence of a disease flare from week 24 to week 48, based on the ACR preliminary definition of disease flare in juvenile arthritis.Forty-one patients were enrolled. At week 24, treatment with etanercept resulted in response rates of 93%, 93%, 80%, 56%, and 54% based on the ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria, respectively. In addition, a marked decrease in all disease activity measures was observed. The mean number of tender joints, swollen joints, and joints with active arthritis decreased by 91%, 97%, and 94%, respectively. Physician's global assessment of disease activity, parent's assessment of patient's overall well-being, and the Childhood Health Assessment Questionnaire disability index improved by 91%, 80%, and 86%, respectively. The number of tender enthesis sites and total scores for back pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, and Juvenile Arthritis Disease Activity Score based on 10-joint counts (JADAS10) decreased by 75%, 72%, 81%, 72%, 85%, and 87%, respectively. In phase II, 38 patients were randomly assigned to receive placebo (n = 18) or to continue receiving etanercept (n = 20). Up to week 48, 12 disease flares occurred, in 9 patients receiving placebo and 3 patients receiving etanercept (odds ratio 6.0, P = 0.02). There were no serious infections, malignancies, or deaths.In this study of patients with the ERA category of JIA, etanercept proved effective, as indicated by high ACR Pedi response rates and JADAS10 response rates at week 24. Patients who continued treatment with etanercept had significantly fewer flares than those who received placebo, although 50% of patients in the placebo group did not experience a flare. Treatment suspension may be a consideration for patients with the ERA category of JIA who achieve remission.

ClinicalTrials.gov identifier: NCT00095173 [Abstract] Objective. The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period, a 6‐month double‐blind withdrawal period, and a long‐term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient‐reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Methods. Patients enrolled in the phase III trial could enter the open‐label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double‐blind period. Results. One hundred fifty‐three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient‐years) of adverse events decreased during the LTE phase (433.61 events during the short‐term phase [combined lead‐in and double‐blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Conclusion. Long‐term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality‐of‐life benefits in patients with JIA.

Objective To describe the disease characteristics of patients with juvenile idiopathic arthritis (JIA) included in an inception cohort, to analyse how many patients from each JIA category reach an inactive disease state within the first year of specialised care and to determine predictors for attaining inactive disease. Methods Patients with JIA were enrolled in this study at 11 large German paediatric rheumatology units within the first 12 months after diagnosis. Laboratory and clinical parameters such as JIA core criteria and data on the medication used were collected every 3 months. Non-parametric statistical testing was performed for the comparison of the JIA core criteria at follow-up. Generalised linear models were used to analyse differences in the rates at which inactive disease was reached and to determine potential predictors. Results Of the 695 patients with JIA included in this analysis, approximately 75% experienced a period of inactive disease under treatment with disease-modifying antirheumatic drugs and systemic steroids in most cases with systemic-onset JIA or polyarthritis at least once during the first 12 months in ICON. Significant improvements were observed in all JIA core criteria, in disease activity and in functional status from baseline to the 12-month follow-up. Younger age at onset, a shorter duration between symptom onset and diagnosis and a positive antinuclear antibody status increased the probability of attaining an inactive disease state. Conclusions The 12-month outcome of JIA was good under real-life conditions, with half of the patients having attained inactive disease with contemporary treatments. Since a short duration between symptom onset and diagnosis was correlated to a period of inactive disease, children suspected of having JIA should be transferred to specialised care as soon as possible.

Objective To describe the long-term outcome of juvenile idiopathic arthritis (JIA). Methods All patients with JIA referred to a pediatric rheumatology center between 1978 and 1988 were identified and invited to undergo an assessment. Patients with JIA from a population-based cohort from East Berlin were included. The outcome assessment considered changes in body function and structure (e.g., mortality, joint abnormalities, disease activity), activities at the individual level (Health Assessment Questionnaire), and participation in society (e.g., mobility, educational and vocational background). Results Of 260 eligible patients, 215 (83%) were evaluated. Subtypes of JIA at disease onset included oligoarthritis (40%), polyarthritis (14%), systemic arthritis (14%), psoriatic arthritis (1%), enthesitis-related arthritis (15%), and other arthritis (16%). Followup was conducted after a median of 16.5 years. No deaths occurred in this cohort. At followup, approximately half of the patients had active disease and/or changes in body structures to a variable extent. Approximately one-third of patients rated themselves as being functionally limited. Patients demonstrated good social integration: few mobility problems were reported, and the educational achievements of patients were higher and their rate of unemployment was lower compared with the age-matched population. No significant differences in outcome were found between the population-based and the referral-based cohorts. Conclusion Even though approximately half of the JIA patients had more or less distinctive changes in body function and/or structure after a disease duration of >15 years, fewer than 10% were severely disabled or handicapped. Because JIA often persists into adulthood, long-term followup and care are necessary.

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.

Background Juvenile idiopathic arthritis (JIA) of the temporomandibular joint (TMJ) can cause severe growth disturbances of the craniomandibular system. Antigen-induced arthritis (AIA) of the rabbit TMJ is simulating the inflammatory process of the TMJ in JIA. The aim of this study was to investigate the effect of a systemic administration of methotrexate (MTX) on AIA in rabbits by means of three different histological staining methods. Methods After sensitization, a bilateral arthritis of the TMJ was induced by an intra-articular administration of ovalbumin in 12 New Zealand white rabbits aged 10 weeks. From the 13th week of age, six of the 12 rabbits received weekly intramuscular injections of MTX, and the other six animals remained without therapy. Another six animals served as controls, receiving no treatment or intra-articular injections at all. After euthanasia at the age of 22 weeks, all TMJs were retrieved en bloc. Sagittal sections were cut and stained with haematoxylin–eosin (H-E), Safranin-O for the evaluation of the Mankin score and tartrate-resistant acid phosphatase (TRAP). Results In the arthritis group, a chronic inflammation with degeneration of the articular cartilage was visible. In the MTX group, the signs of cartilage degeneration were significantly reduced compared with the arthritis group. In contrast, the joints in the control group were inconspicuous. A correlation between the Mankin score and TRAP-positive cells could be found. Conclusions Systemic administration of MTX seems to have a positive effect upon the inflammatory process in the rabbit TMJ but fails to eliminate the sign of arthritis completely.

Background Juvenile idiopathic arthritis (JIA) of the temporomandibular joint (TMJ) can cause severe growth disturbances of the craniomandibular system. Antigen-induced arthritis (AIA) of the rabbit TMJ is simulating the inflammatory process of the TMJ in JIA. The aim of this study was to investigate the effect of a systemic administration of the tumor necrosis factor-alpha (TNF-α) antagonist etanercept on AIA in rabbits by means of three different histological staining methods. Methods After sensitization, a bilateral arthritis of the TMJ was induced and maintained by repeated intra-articular administrations of ovalbumin in 12 New Zealand white rabbits aged 10 weeks. From the 13th week of age, 6 of the 12 rabbits received weekly subcutaneous injections of etanercept, and the other 6 animals remained without therapy. Another 6 animals served as controls, receiving no treatment or intra-articular injections at all. After euthanasia at the age of 22 weeks, all TMJs were retrieved en bloc. Sagittal sections were cut and stained with hematoxylin–eosin (H-E), Safranin-O for the evaluation of the Mankin score, and tartrate-resistant acid phosphatase (TRAP). Results In the arthritis group, a chronic inflammation with degeneration of the articular cartilage was visible. In the etanercept group, the signs of cartilage degeneration were significantly reduced but present. In contrast, the joints in the control group were inconspicuous. A strong correlation between the Mankin score and TRAP-positive cells could be found. Conclusions Antigen-induced arthritis causes severe damage in the TMJ of young rabbits. An improvement seems to be achievable by a systemic administration of etanercept.

das Jahr 2015 hat uns in vielerlei Hinsicht herausgefordert, 2016 wird dem nicht nachstehen. Das schliest alle Bereiche unseres Lebens ein, naturlich auch unsere kinderrheumatologische Tatigkeit. Fordern werden uns die Patienten, die wir sehen, die Informationen und Kenntnisse, die es zu erwerben gilt, und die Forschungsaufgaben, die zu losen sind. Dinge, die in 2015 auf den Weg bzw. weiter voran gebracht wurden, werden uns bei der Aufgabenbewaltigung unterstutzen. So wurde zum Jahreswechsel nach intensiver Arbeit die neue Webseite der PRINTO (Pediatric Rheumatology International Trials Organisation) mit aktualisierten Informationen zu den wichtigsten kinderrheumatologischen Krankheitsbildern, zu Selbsthilfeorganisationen und Kinderrheumazentren in 29 Landern freigeschaltet (http://www. printo.it/pediatric-rheumatology/). Dieses Informationsangebot fur betroffene Patienten und deren Familien, Interessierte und Kollegen stellt eine wertvolle Unterstutzung im klinischen Alltag dar. Es gestattet, uber im Kindesalter auftretende z. T. sehr seltene Krankheitsbilder (z. B. die juvenilen Kollagenosen, Vaskulitiden und autoinflammatorische Erkrankungen, den Morbus Behcet, aber auch Schmerzsyndrome) allgemein verstandlich aufzuklaren und aktuelle Therapieoptionen aufzuzeigen. Geschaffen wurde diese Informationsquelle unter Federfuhrung von Kollegen aus Holland und Italien mit der finanziellen Unterstutzung der EU von Kinderrheumatologen aus vielen Landern. Auch aus Deutschland haben 17 Kinderrheumatologen hieran mitgearbeitet.

Paediatric rheumatic illnesses are among the most common chronic diseases in children and adolescents. These illnesses have important impacts on patient’s body functions and structures, activities, and social participation. Knowledge about the effect and consequences of these diseases is necessary to formulate appropriate aims of treatments. The multidimensional outcomes of paediatric rheumatic diseases and their measurement are reviewed in this chapter. Outcome measurement is complex in patients who have growing needs and changing expectations as they develop, especially in chronic conditions that have a variable and often unpredictable course, such as juvenile idiopathic arthritis, juvenile systemic lupus erythematosus, and juvenile dermatomyositis. Considerable work has been conducted recently in an effort to better define and value global outcomes for these patients. New and reliable outcome measures have been developed to capture all aspects of the patient’s life and integrate the patients’ perspective. Existing outcome studies of paediatric rheumatic diseases have consistently shown, even though differing in their methodology, that patient outcomes have improved over the last decade. More patients with chronic inflammatory rheumatic conditions survive into adulthood, and patients’ long-term health, functional, and quality of life outcomes have improved. However, outcomes are still less than ideal. More than one-half of the patients with paediatric rheumatic diseases have ongoing active disease in early adulthood. Over one-third have evidence of disability and organ damage, with each underlying disease being associated with specific complications. Clearly, given the inherent potential for disability, morbidity, even mortality, young people with paediatric-onset rheumatic diseases require ongoing medical care into adulthood.

Juvenile idiopathic arthritis (JIA) is the most common systemic disease associated with uveitis in childhood. The frequency of JIA-associated uveitis (JIAU) varies geographically, and between ethnicities. Uveitis risk is high in JIA associated with oligoarthritis, young age at arthritis onset and ANA positivity. Gender alters risk for the incidence of JIA and the severity of JIAU. Familial cases support the possible role of genetic influences in the pathogenesis. Arthritis typically precedes the uveitis, but uveitis may occur up to seven years following the arthritis onset. Although complications still occur, the frequency of bilateral blindness has dropped, probably by both improved screening of high-risk patients with JIA, and the increased use of early immunosuppression. However, there is still continuing persistence of JIAU into adulthood. For improvement of epidemiological knowledge of this complicated disease, large, well-defined, long-term population-based registries are needed with the application of universally agreed case definitions and outcome measures.

Improvement in health-related quality of life (HRQOL) is an important therapy goal in the treatment of patients with juvenile idiopathic arthritis (JIA). We investigated the 12-month course of HRQOL in patients with JIA after the start of therapy with etanercept and identified its determining factors.Children with JIA were enrolled in the BiKer (Biologics in Pediatric Rheumatology) registry at the start of etanercept treatment. Children were prospectively followed in the first year of treatment and completed the Pediatric Quality of Life Inventory (PedsQL) at each occasion. The change in HRQOL was investigated by random-effect regression models. The time-varying variables pain and inactive disease were used for predicting the change in HRQOL. Inactive disease was defined by the Wallace et al criteria and pain was assessed on a visual analog scale (range 0-100).The children (n = 61) had a mean age of 10.6 years and a mean disease duration of 3.4 years at the start of etanercept. The mean PedsQL total score was 75. The PedsQL total score increased at a rate of 2.8 units per month (P0.001) in the first 6 months of treatment, up to a level of 89.7. A low HRQOL score was significantly highly associated with the number of tender joints, functional restrictions, pain, disease activity, and the existence of a comorbid condition at baseline. Inactive disease and reduced pain predicted better HRQOL under etanercept treatment.HRQOL was dramatically improved in children who started etanercept treatment. Inactive disease and lower pain were important predictors for improvement of HRQOL over time.

This study aims to assess the prevalence of comorbidities in adult JIA and the impact of comorbidity on patients' perceived health state.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.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 (p0.001, each), and a lower physical and mental health-related quality of life than those without comorbidities (p0.001 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.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.

Objectives Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease affecting children. Even if remission is successfully induced, about half of the patients experience a relapse after stopping anti-inflammatory therapy. The present study investigated whether patients with JIA at risk of relapse can be identified by biomarkers even if clinical signs of disease activity are absent. Methods Patients fulfilling the criteria of inactive disease on medication were included at the time when all medication was withdrawn. The phagocyte activation markers S100A12 and myeloid-related proteins 8/14 (MRP8/14) were compared as well as the acute phase reactant high-sensitivity C reactive protein (hsCRP) as predictive biomarkers for the risk of a flare within a time frame of 6 months. Results 35 of 188 enrolled patients experienced a flare within 6 months. Clinical or standard laboratory parameters could not differentiate between patients at risk of relapse and those not at risk. S100A12 and MRP8/14 levels were significantly higher in patients who subsequently developed flares than in patients with stable remission. The best single biomarker for the prediction of flare was S100A12 (HR 2.81). The predictive performance may be improved if a combination with hsCRP is used. Conclusions Subclinical disease activity may result in unstable remission (ie, a status of clinical but not immunological remission). Biomarkers such as S100A12 and MRP8/14 inform about the activation status of innate immunity at the molecular level and thereby identify patients with unstable remission and an increased risk of relapse.

Objective To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)–associated uveitis. Methods The literature relating to outcome measures used in studies of uveitis in childhood and adolescence was reviewed. A set of core outcomes and domains was established using the Delphi process. This was reviewed by a representative multinational interdisciplinary working group. Nominal group technique consensus was reached on face and content validity of the range and content of the domains. The outcomes and the appropriate instruments for uveitis trials were adapted to the age ranges of patients with JIA-associated uveitis. Results Consensus was reached that data should be reported at defined time points in longitudinal studies with patients stratified by prognostic markers. Visual acuity testing should be age appropriate. The severity of uveitis (measured as anterior chamber cell grade) and duration of active inflammation should be documented. Visually significant structural complications should be recorded and quantified with standard measures. The responses to treatment and corticosteroid-sparing effects of treatment should be documented. Patient-reported disease activity and age-specific uveitis-related quality of life should be reported using appropriate questionnaires. Conclusion The proposed outcome measures in JIA-associated uveitis should aid in the standardization and comparison of future RCTs of the treatment regimens for this disease. The proposed outcome measures will be verified in a prospective validation study.

Investigators mainly from North America have established a new classification of juvenile idiopathic arthritis (JIA) by creating treatment groups, levels of disease activity and prognostic features [3]. After scanning the available literature for controlled trials the authors recommend treatment options. Due to the lack of published evidence these authors could not find an indication for the use of systemic steroids in chronic synovitis. Since this drug may be very useful for patients with JIA and its introduction predates evidence-based medicine, it should not be removed from treatment algorithms, but should be tested in controlled trials. Further topics of discussion relate to treatment with tocilizumab, rituximab, methotrexate, hydroxychloroquine, abatacept and to varying levels of evidence in treatment recommendations. Beukelman et al. will have a lasting impact on the treatment of JIA. European Societies for Pediatric Rheumatology should participate in future developments.

Background/Purpose: In the phase 3 TENDER trial of tocilizumab (TCZ) in patients with systemic juvenile idiopathic arthritis (sJIA), decreases in neutrophil count were commonly observed. The purpose of this study was to determine whether neutropenia was associated with increased risk for infection and to investigate variables associated with the development of neutropenia in patients treated with TCZ for up to 2 years in TENDER. Methods: One hundred twelve children with active, persistent sJIA were randomly assigned 2:1 to receive TCZ based on body weight (12 mg/kg 0.3). Conclusion: No trend for association between neutropenia and increased risk for infection was observed in the TENDER trial. Background methotrexate, and somewhat younger age, was associated with increased risk for neutropenia, whereas TCZ exposure and concurrent glucocorticoid use were not.

Background/Purpose: The long-term efficacy and safety of intravenous abatacept in patients (pts) with juvenile idiopathic arthritis (JIA) have been reported previously from the Phase III AWAKEN trial ([1, 2]). Here, we report efficacy, safety and pt-reported outcomes from the open-label, long-term extension (LTE) of AWAKEN, with up to 7 years of follow-up. Methods: Pts entered the LTE if they were JIA ACR 30 non-responders (NR) at the end of the 4-month lead-in period (abatacept only), or if they received abatacept or placebo (pbo) in the 6-month double-blind (DB) period. The Child Health Questionnaire was used to evaluate health-related quality of life (HRQoL); physical (PhS) and psychosocial (PsS) summary and pain scores were analyzed. Pain was assessed by parent global assessment using a 100 mm visual analog scale. Efficacy and HRQoL evaluations are reported up to Day 1765 (~ Year 5.5). Safety is presented for the cumulative period (lead-in, DB and LTE), for all pts who received abatacept during the LTE. Results: Of the 153 pts entering the LTE (58 from DB abatacept group, 59 from DB pbo group, 36 NR), 69 completed the trial (29 abatacept, 27 pbo, 13 NR). For pts treated in the LTE, mean (range) exposure to abatacept was 53.6 (5.6–85.6) months. During the LTE, incidence rates of AEs and serious AEs per 100 pt-years were 209.1 and 5.6. Thirty pts (19.6%) had serious AEs; most were unrelated and were musculoskeletal (8.5%) or infectious events (6.5%). No malignancy was reported. There was one death (accidental; unrelated). At Day 169, JIA ACR 50 and 70 response rates were 79.3% and 55.2% in the abatacept group, and 52.5% and 30.5% in the pbo group; 31.0% and 10.2% of pts in the abatacept and pbo groups, respectively, had inactive disease. By Day 1765, JIA ACR 50 and 70 response rates were 93.9% and 78.8% in the abatacept group, and 80.0% and 63.3% in the pbo group; 51.5% and 33.3% had inactive disease. In the NR group, 69.2% and 53.8% of pts achieved JIA ACR 50 and 70 responses at Day 1765, and 30.8% had inactive disease. In pts who entered the LTE, mean baseline PhS scores were below the range for healthy children (abatacept 30.2, pbo 31.0, NR 29.5). At Day 169, 38.3% of pts had reached a PhS score >50 ((1). By the end of the LTE, 43.5% of pts had reached a PhS score >50. At baseline, mean PsS scores for those who entered the LTE were slightly lower than the mean for healthy children (abatacept 43.5, pbo 44.2, NR 47.0). At Day 169, 54.9% of pts had a PsS score >50 (1). By Day 1765, 58.1% of pts had reached a PsS score >50. At baseline, the mean pain score was 42.9. By Day 169, 13.9% of pts were considered pain free (pain score = 0); this was maintained over the LTE (1). Table 1. NR(%) n=36 DB abatacept (%) n=58 DB pbo (%) n=59 Total (%) n=153 Day 169 (start of LTE) PhS >50 20.0 46.2 41.2 38.3 PsS >50 50.0 57.7 54.9 54.9 Pain free 0 20.4 15.7 13.9 Day 1765 (end of LTE) PhS >50 33.3 55.6 34.8 43.5 PsS >50 58.3 55.6 60.9 58.1 Pain free 0 17.9 16.0 13.1 Conclusion: Long-term treatment with abatacept for up to 7 years was associated with consistent safety, and sustained clinical efficacy and quality-of-life benefits in patients with JIA who remained on therapy.

Objectives. Etanercept, a recombinant TNF receptor fusion protein, has been approved for the treatment of resistant polyarticular course juvenile idiopathic arthritis at a dosage of 0.4 mg/kg twice weekly in children older than 4 years. In adult patients, efficacy and safety of etanercept 25 mg twice weekly was comparable with 50 mg once weekly. Therefore, safety and efficacy of etanercept once weekly 0.8 mg/kg up to 50 mg s.c. was evaluated in a 3 month open label trial. Methods. Twenty patients 4 to 17 years old received 0.8 mg of etanercept per kilogram of body weight subcutaneously once weekly for 3 months in an open multicentre trial. Active polyarticular disease was defined by the presence of five or more active joints with swelling, alternatively with pain or tenderness combined with limitation of motion. Safety assessments were based on adverse events (AEs) reports. Efficacy was assessed using the PedACR30/50/70 criteria. Results. At the start of treatment the patients showed high disease activity. A rapid reduction of all disease activity parameters was observed. A PedACR30/50/70 response was reached by 75%/35%/10% of patients after 4 weeks, 90%/75%/35% after 8 weeks and 95%/75%/75% after 12 weeks of treatment. There were 37 AEs, none of them serious, with injection site reactions and minor infections being the most frequent. There was no drop out. Long-term follow-up of the patients will be carried out in the German JIA Registry. Conclusion. Treatment with etanercept once weekly using a double dosage leads to a significant improvement of disease activity in patients with active polyarticular course juvenile idiopathic arthritis and is well tolerated.

Objective:To assess whether the removal of aids/devices and/or help from another person in the Childhood Health Assessment Questionnaire (C-HAQ) leads to a significant change in the disability index (DI) score and responsiveness in juvenile idiopathic arthritis (JIA).Methods:Changes in the C-HAQ DI score in a cross-sectional sample of 2663 children with JIA and in 530 active patients with JIA in a trial of methotrexate (MTX) were compared.Results:Patients in the MTX trial had higher disease activity and disability than the cross-sectional sample. The frequency of aids/devices (range 1.2–10.2%) was similar between the two samples, while help (range 5.3–38.1%) was more frequently used in the MTX group. Correlation between disease severity variables and the two different C-HAQ DI scoring methods did not change substantially. There was a decrease in the C-HAQ DI score for both the cross-sectional (mean score from 0.64 with the original method to 0.54 without aids/devices and help, pConclusion:The removal of aids/devices and help from the C-HAQ does not alter the interpretation of disability at a group level. The simplified C-HAQ is a more feasible and valid alternative for the evaluation of disability in patients with JIA.

Open Access Poster presentation Does incorporation of aids/devices and help, make a difference in the childhood health assessment questionnaire disability index? Analysis from the printo juvenile idiopathic arthritis database C Saad-Magalhaes*, A Pistorio, A Ravelli, R Brik, D Mihaylova, R Ten Cate, B Andersson-Gare, V Ferriani, K Minden, P Hashkes, M Rygge, MJ Sauvain, H Venning, A Martini and Ruperto for the Paediatric Rheumatology International Trials Organisation (PRINTO) N

Methods At each study site an independent ethics committee approved the protocol, and each patient's parent gave written informed consent (EudraCT No. 2007-00025534). 20 patients 4 to 17 years old were included and received 0.8 mg/kg bw. of etanercept subcutaneously once weekly for 12 weeks "Active" polyarticular disease was defined by the presence of five or more active joints. PedACR30/50/70 criteria were calculated.

Das Gelenkrheuma im Kindesalter umfasst eine heterogene Gruppe von Erkrankungen, deren gemeinsames Merkmal die chronische Gelenkentzundung unbekannter Ursache ist. Die Identifizierung dieser Erkrankung erfolgt, bei weitgehend unbekannter Atiopathogenese und fehlenden pathognomonischen Krankheitsmerkmalen, anhand einer Kombination von klinischen, labormedizinischen und anderen Merkmalen.

A young girl suffering from ankle pain occurring after gymnastics classes was referred to the rheumatology department by an orthopedic surgeon because a rheumatological condition was suspected to cause her symptoms. MRI was useful in pointing to the correct diagnosis of accessory navicular bone (AN). The morphological classification of ANs is discussed and the imaging modalities for diagnosis are presented.

Objective To compare MRI evaluation of a painful hindfoot of patients with spondyloarthritides (SpA) on low-field (0.2 T) versus high-field (1.5 T) MRI. Materials and methods Patients with SpA and hindfoot pain were randomly referred to either high-field or low-field MRI. Twenty-seven patients were evaluated (male/female: 17:10; mean age: 39 ± 1.4 years). Fifteen patients were examined by low-field and 12 by high-field MRI. Two patients (evaluated by high-field MRI) were excluded. Images were separately read by two radiologists who later reached a consensus. In each patient the prevalence of erosions, fluid, synovitis or bone marrow edema of the hindfoot joints, tendinosis or tenosynovitis of tendons, enthesitis of the plantar fascia and Achilles tendon and retrocalcaneal bursitis were recorded. Clinical and demographic parameters were comparable between both groups. Results MRI evaluation of joints and tendons of the hindfoot revealed no significant differences in patients with SpA groups for all parameters. Analyzing all joints or tendons together, there was no statistically significant difference between the two groups. Conclusion Low-field and high-field MRI provide comparable information for evaluation of inflammatory hindfoot involvement. Thus, low-field MRI can be considered as a reliable diagnostic tool for the detection of hindfoot abnormalities in SpA patients.

Juvenile rheumatic diseases have important impacts on health, i.e. on patients' body functions and structures, activities, and social participation. The identification and treatment of these disorders is costly. Treatment involves periods of hospitalization, the use of physicians and other professional services, drugs and other treatments. Frequent outpatient visits are needed, as may be surgery. This all imposes a large financial burden on health-care systems and on families of children who suffer from rheumatic illnesses. Costs borne by families are both out-of-pocket as well as related to time spent in providing care, which may involve loss of income. Of course, the burdens are not only monetary, and they sometimes continue for life. The measurement of the different types of cost is essential to get a full picture of the burden of childhood-onset rheumatic illnesses. This chapter presents data on the costs of these illnesses, and introduces methodologies and their limitations for cost evaluation within paediatric rheumatology.

Objective To validate and promulgate a core set of outcome measures for the evaluation of response to treatment in patients with juvenile systemic lupus erythematosus (SLE). Methods In 2001, a preliminary consensus-derived core set of measures for evaluating the response to therapy in juvenile SLE was established. In the present study, the core set was validated through an evidence-based, large-scale data collection process that led to the enrollment of 557 patients from 39 different countries. Consecutive patients with active disease were assessed at baseline and after 6 months. The validation procedures included assessment of feasibility, responsiveness, discriminant and construct ability, agreement in the evaluation of response to therapy between physicians and parents, redundancy, internal consistency, and ability to predict a therapeutic response. Results The following clinical measures were found to be feasible and to have good construct validity, discriminative ability, and internal consistency; furthermore, they were not redundant, proved responsive to clinically important changes in disease activity, and were associated strongly with treatment outcome and thus were included in the final core set: 1) physician's global assessment of disease activity, 2) global disease activity measure, 3) 24-hour proteinuria, 4) parent's global assessment of the patient's overall well-being, and 5) health-related quality of life assessment. Conclusion The members of PRINTO propose a core set of criteria for the evaluation of response to therapy that is scientifically and clinically relevant and statistically validated. The core set will help standardize the conduct and reporting of clinical trials and assist practitioners in deciding whether a patient with juvenile SLE has responded adequately to therapy.

To investigate the prevalence of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) among outpatients presenting with recurrent fevers and clinical features consistent with TRAPS.Mutational screening was performed in affected members of 18 families in which multiple members had symptoms compatible with TRAPS and in 176 consecutive subjects with sporadic (nonfamilial) "TRAPS-like" symptoms. Plasma concentrations of soluble tumor necrosis factor receptor superfamily 1A (sTNFRSF1A) were measured, and fluorescence-activated cell sorter analysis was used to measure TNFRSF1A shedding from monocytes.Eight novel and 3 previously reported TNFRSF1A missense mutations were identified, including an amino acid deletion (Delta D42) in a Northern Irish family and a C70S mutation in a Japanese family, both reported for the first time. Only 3 TNFRSF1A variants were found in patients with sporadic TRAPS (4 of 176 patients). Evidence for nonallelic heterogeneity in TRAPS-like conditions was found: 3 members of the "prototype familial Hibernian fever" family did not possess C33Y, present in 9 other affected members. Plasma sTNFRSF1A levels were low in TRAPS patients in whom renal amyloidosis had not developed, but also in mutation-negative symptomatic subjects in 4 families, and in 14 patients (8%) with sporadic TRAPS. Reduced shedding of TNFRSF1A from monocytes was demonstrated in vitro in patients with the T50M and T50K variants, but not in those with other variants.The presence of TNFRSF1A shedding defects and low sTNFRSF1A levels in 3 families without a TNFRSF1A mutation indicates that the genetic basis among patients with "TRAPS-like" features is heterogeneous. TNFRSF1A mutations are not commonly associated with nonfamilial recurrent fevers of unknown etiology.

To describe the long-term outcome of juvenile idiopathic arthritis (JIA).All patients with JIA referred to a pediatric rheumatology center between 1978 and 1988 were identified and invited to undergo an assessment. Patients with JIA from a population-based cohort from East Berlin were included. The outcome assessment considered changes in body function and structure (e.g., mortality, joint abnormalities, disease activity), activities at the individual level (Health Assessment Questionnaire), and participation in society (e.g., mobility, educational and vocational background).Of 260 eligible patients, 215 (83%) were evaluated. Subtypes of JIA at disease onset included oligoarthritis (40%), polyarthritis (14%), systemic arthritis (14%), psoriatic arthritis (1%), enthesitis-related arthritis (15%), and other arthritis (16%). Followup was conducted after a median of 16.5 years. No deaths occurred in this cohort. At followup, approximately half of the patients had active disease and/or changes in body structures to a variable extent. Approximately one-third of patients rated themselves as being functionally limited. Patients demonstrated good social integration: few mobility problems were reported, and the educational achievements of patients were higher and their rate of unemployment was lower compared with the age-matched population. No significant differences in outcome were found between the population-based and the referral-based cohorts.Even though approximately half of the JIA patients had more or less distinctive changes in body function and/or structure after a disease duration of15 years, fewer than 10% were severely disabled or handicapped. Because JIA often persists into adulthood, long-term followup and care are necessary.

To describe the health care provision for children and adolescents with chronic arthritides in Germany in 1998.Data were analyzed from the German pediatric rheumatologic database of the year 1998. It contains clinical and patient questionnaire data for 2488 patients with rheumatic diseases seen at 18 pediatric rheumatology units.A total of 1811 of all patients recorded in the database had chronic arthritides--931 with juvenile chronic arthritis, 86 with juvenile spondyloarthropathy, and 65 with juvenile psoriatic arthritis were considered in the analysis. These patients seen by pediatric rheumatologists had a median age of 10 years and a median disease duration of 4 years. The majority were being treated at pediatric rheumatology disease centers and at universities. Nonsteroidal antiinflammatory drugs were the most commonly used drugs for all forms of chronic arthritides. Almost half the patients with chronic arthritides received disease modifying antirheumatic drugs, with methotrexate the most frequently prescribed agent. While the majority of patients reported having physiotherapy, low prescription rates were noted for comprehensive measures such as occupational therapy and patient education. Only a few patients showed severe functional limitation, 2% of them being rated in Steinbrocker class III or higher. While the patients' functional limitation correlated with disease activity, neither disease duration nor sex, arthritis subgroup nor time span to the first visit at the rheumatology unit had any relevant influence on functional status.The data reveal the spectrum of patients with chronic arthritides seen by German pediatric rheumatologists, as well as the treatment patterns of their physicians.

Background/Purpose: The outcome of children with JIA refractory to disease-modifying antirheumatic drugs (DMARDs) has improved significantly since Etanercept became available. The objectives were to analyse data from the German Biologics JIA Registry (BiKeR) and to report on practice changes of the last twelve years. Methods: Baseline demographics, pre-treatment, concomitant treatment, clinical characteristics and disease activity parameters and outcome have been prospectively documented in BiKeR since 2000. Efficacy was determined using the PedACR response criteria, the JADAS-10 and the proposed criteria for inactive disease on medication. Results: From 2000 to 2012 1678 children with JIA on Etanercept with a total of 11,474 visits have been enrolled in BiKer (3424.2 total patient-years). The median disease duration at treatment start decreased from 4.5 to 2 years. While initially children have been pre-treated with numerous antirheumatic agents, including cytotoxic agents, pre–treatment markedly decreased by a mean 6.3 (median 4.3) to 0.99 (median 1.0) DMARDssol;patient. Concomitant treatment initially consisted of corticosteroids in 83%, Methotrexate in 95% and other DMARDs in 45% of children compared to 40%, 74% and 6.7% respectively in 2012. At Registry start, 26% of newly enrolled children belonged to the systemic JIA category compared to only 1% in 2012. In contrast, the rate of children with enthesitis related arthritis increased from 2% to 16%. The median JADAS-10 in 2000 compared to 2012 was significantly higher at treatment start (24.4+/−6.8 vs. 13.3+/−6.2) and remained higher after 6 months on treatment (7.5+/−7.2 vs. 4.5+/−5.2). The number of patients that have reached a PedACR 70 after 12 months on treatment increased from 41% starting in 2000 to 51% of patients starting in 2012. Inactive disease within one year was documented initially in 20% of children and increased to 43% in 2012. Conclusion: In recent years, children with JIA have been treated earlier, received less pre- and concomitant treatment with corticosteroids as well as with DMARDs. Patients have shown a markedly better outcome reflected in the higher PedACR response, lower JADAS-10 and higher rate of patients with inactive disease after one year on treatment. These data suggest that early disease control and better pre–selection of patients who need biologics are important to improve outcome in children with JIA.

Diagnosis of Lyme arthritis (LA) in children and adolescents may be difficult due to non-specific clinical manifestations and unreliable serological tests for antibodies to Borrelia burgdorferi. In a national prospective study, 186 children with arthritis were examined in whom the attending physicians had considered the diagnosis of LA. Ultimately, LA was confirmed in 87 patients and these were compared with the remaining 99 children in whom arthritis was attributable to other causes. In comparison to patients with other causes of arthritis, patients with LA had a higher frequency of episodic arthritis and initial knee joint arthritis, reported tick bites more frequently, were older, had a lower frequency of initial arthralgias, and there were fewer large joints involved. A score was developed in a group of these patients and tested in a second group. It enabled patients with LA to be distinguished from those with other causes of arthritis: within a range from 12 to −7 points, a score of 2.5 or less excluded LA whereas 6 or more points were highly indicative of LA. If only those children with a score result between 2.5 and 6 had been tested for antibodies to B. burgdorferi, the number of tests would have been reduced by 63%. Conclusion Careful analysis of clinical presentation and use of a clinical score may help in distinguishing LA from other causes of arthritis and thus reduce unnecessary and expensive testing and uninterpretable test results.

Background The ACR paediatric criteria used in clinical trials are validated to analyse the response to a treatment in comparison to baseline but does not indicate the absolute disease activity nor the absolute improvement. This problem has been overcome by the development of the JADAS in 3 different versions. Methods The JADAS10 and -71 has been used to analyse the efficacy of Etanercept treatment in JIA patients using data of the BIKER registry. It includes 4 measures: physician global assessment of disease activity, parent/patient global assessment of well-being, active joint count, and erythrocyte sedimentation rate. Results A total 1470 JIA patients treated with Etanercept and followed by the GERMAN BIKER registry have been used for analysis. At baseline, patients with systemic JIA had highest JADAS71 (24.5±14.2; median 21, range 2-72) and JADAS10 (21.4±9.3; 21, 2-39), followed by RF+ polyarthritis (JADAS71 24.3±14; 22, 0-63; JADAS10 19.4±8.0; 20, 0-35) and RF- polyarthritis (JADAS71 23.1±14; 20, 0-85; JADAS10 18.4+/7.2; 18, 0-39). Patients with extended oligoarthritis had moderate JADAS71 (18.4±8.4) and -10 (17.5±7.3) at baseline, while patients with enthesitis related arthritis and psoriasis arthritis had lowest levels. The JADAS71 and the JADAS 10 (table 1) in the total JIA patient cohort markedly decreased. Patients of all JIA categories demonstrated improvement upon treatment within months. The residual disease activity (JADAS10; -71) remained highest in patients with systemic JIA (7.7; 9.3), RF+polyJIA (4.7; 5.0), RF-Poly (5.2; 5.9) and PsA (4.8; 5.4) while patients with extOligo, (2.6; 2.6), ERA (4.0; 4.1). No mayor differences were observed between the two scores. Patients treated with combination of Etanercept and Methotrexate at baseline had slightly higher JADAS71 and -10 score (21.2±12.5 and 18.1±7.0) than those receiving Etanercept monotherapy (10.3±10.1 and 16.8±7.4). At month 6, combination treatment resulted to a decrease of the JADAS71 and -10-score of 14.3±12.1 and 11.9±8.4 points and mono therapy to a decrease of 13.8±11.5 and 12.1±8.0 points which was comparable. At month 6 slightly more patients with Methotrexate achieved a JADAS score of 0 (21% vs.17%). At baseline, no obvious differences in JADAS71 or -10 was noted between those patients with a disease duration 2 years. While the decrease in both JADAS71 and -10 also ws comparable, more patients with a disease duration Conclusions The JADAS71 and JADAS10 scores could easily be performed and showed significant differences between the JIA categories. Patients of all JIA categories showed improvement, while those with a more serious disease also had highest residual disease activity. Positive effects of an early initiation of Etanercept treatment could also be demonstrated. Disclosure of Interest G. Horneff Grant/Research support from: Pfizer, Abbott, Roche, T. Niehues: None Declared, H. Huppertz: None Declared, J. Haas: None Declared, K. Minden: None Declared

Background Combination treatment of Etanercept with corticosteroids and/or Methotrexate has been shown to have an impact on the occurrence of adverse events. (1) Methods The data base of the German BIKER registry documenting the treatment of juvenile idiopathic arthritis patients (JIA) with Etanercept since 2001 has been used to analyse the impact of treatment on the discontinuation of concomitant drug treatment, especially of corticosteroids, NSAIDs, Methotrexate and further DMARDs. Results 1276 JIA patients have been identified with a baseline visit and at least 1 follow up visit. At baseline, 1039 (81.4%) received NSAIDs, 582 (44%) received corticosteroids (median dosage 5 mg/day) and 928 (72.7%) received Methotrexate. 233 (18.3%) received other DMARDs (Azathioprine (5.5), Cyclosporine A (2.3%), Leflunomide (2.3%), Sulfasalazin (4.2%), (OH)Chloroquine (2.1%) as further concomitant treatment. Upon treatment, concomitant pharmacomedical treatment was continuously reduced over time (table). At 12 months 53% of patients received NSAIDs, and 58.9% Methotrexate, 29.3% corticosteroids. In total, 445/928 (48%) patients discontinued Methotrexate with a mean survival of combination with MTX of 34.5 months. 260/582 (45%) of patients discontinued corticosteroids with a mean survival of combination with corticosteroids of 26.5 months. So, corticosteroids have significantly earlier been discontinued than Methotrexate (p=0.006, Hazard ratio 1.2 (1.0-1.4). Of those 83 patients with uveitis as co morbidity, 35 (42%) discontinued MTX with a mean survival of MTX of 43 months. Conclusions Upon treatment with Etanercept, most patients initially received concomitant treatment with NSAIDs, corticosteroids, Methotrexate, and other DMARDs. However these drugs are frequently discontinued, while corticosteroids were discontinued prior to Methotrexate. References Horneff G, De Bock F, Foeldvari I, et al: Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis. 2009 Apr;68(4):519-25. Disclosure of Interest G. Horneff Grant/Research support from: Pfizer, Abbott, K. Minden: None Declared

Tumour necrosis factor receptor associated periodic syndrome (TRAPS) is an autosomal dominant disorder resulting from mutations in the TNFRSF1A gene,1 characterised by recurrent attacks of fever, abdominal pain, severe myalgia, skin rashes, conjunctivitis, and/or periorbital oedema.2,3 These symptoms, which are partially explained by the unopposed action of tumour necrosis factor (TNF) owing to decreased soluble TNF receptor 1 (sTNFRSF1A) serum levels,4 can be alleviated by administration of etanercept, which is a TNFRSF1B (TNFR2) p75:Fc fusion protein.2,5 We describe a family in which one of three affected members with central nervous system (CNS) symptoms developed a demyelinating disorder suspected to be a feature of TRAPS. A 20 year old white man and his 25 year old sister had complained about recurrent attacks of fever, abdominal and loin pain, severe myalgia, skin lesions, sore throat, conjunctivitis, and periorbital oedema since early childhood. These attacks had come at irregular intervals, lasted for 2–3 weeks, and were accompanied by greatly increased acute phase reactants. During childhood both patients had …