Objectives Differential diagnosis in children with prolonged fever is challenging. In particular, differentiating systemic-onset JIA (SJIA) from infectious diseases is difficult. Biomarkers are needed that support the diagnostic work-up. The aim of this study was to validate the usefulness of Myeloid-related protein 8/14 (MRP8/14) measurements in the diagnostic work-up of febrile children and to transfer it to clinical practice. Methods Data for 1110 paediatric patients were included and divided into two cohorts: (cohort A) for validation of MRP8/14 test performance with three different testing systems: the experimental ELISA, commercial ELISA and an innovative (point-of-care test) lateral flow immunoassay (LFIA); (cohort B) to validate the diagnostic accuracy with the two latter assays. Results In cohort A (n = 940), MRP8/14 was elevated in SJIA (12 110 +/- 2650 ng/ml mean +/- 95% CI) compared with other diagnoses (including infections and autoinflammatory diseases; 2980 +/- 510 ng/ml) irrespective of fever and anti-inflammatory treatment (P < 0.001). In untreated patients with fever (n = 195) MRP8/14 levels in SJIA (19 740 +/- 5080 ng/ml) were even higher compared with other diagnoses (4590 +/- 1160 ng/ml) (P < 0.001, sensitivity 73%, specificity 90%). In group B1, the performance of the tests was confirmed in untreated patients with fever (n = 170): commercial ELISA (sensitivity 79%, specificity 89%) and LFIA (sensitivity 84%, specificity 81%). Compared with ferritin, IL-18, ESR, soluble IL-2 receptor and procalcitonin, MRP8/14 showed the best accuracy. Conclusion MRP8/14 serum analyses have been validated as a helpful tool supporting the diagnosis of SJIA in febrile children. The results could be confirmed with commercial ELISA and LFIA enabling a rapid diagnostic point-of-care screening test.

BACKGROUND:New therapeutic strategies for juvenile idiopathic arthritis (JIA) have evolved within the past ten years, and as a result, an update of the 2011 recommendations of the German management guidelines was initiated.METHODS:A systemic literature review was performed, overarching principles were proposed and pre-selected via an online survey followed by two multidisciplinary consensus conferences. Pharmacological and non-pharmacological treatments were discussed, statements were proposed and ultimately agreed upon by nominal group technique (NGT).RESULTS:12 overarching therapeutic principles, as well as 9 recommendations on pharmacological and 5 on non-pharmacological treatments for JIA were agreed upon.CONCLUSION:This report summarizes the recent update of the interdisciplinary, consensus-based German guidelines on the management of JIA. The multi- and interdisciplinary participation of all caregivers was central for this patient-focused update. With these guidelines, physicians can choose an evidence-based approach, which allows better tailored treatment in this vulnerable cohort of children and adolescents.

Die Auseinandersetzung mit der Erkrankung, ihre Akzeptanz und die Krankheitsbewältigung im Alltag stellt für die betroffenen Kinder und Jugendlichen, aber auch für die Familie eine große Herausforderung und nicht selten eine enorme psychische Belastung dar. Das Wissen um die Chronizität der Erkrankung, die Auswirkungen auf die verschiedenen Lebensbereiche, sowie innerpsychische Prozesse (Selbst- und Körperkonzept, innere Balance, Zukunftsplanung etc.) können zu Störungen einer gesunden Psychodynamik führen. Um die Entstehung von psychiatrischen Komorbiditäten zu vermeiden, sollten früh Interventionen erfolgen, die eine optimale Krankheits- und Alltagsbewältigung unterstützen. Dazu zählen v. a. Edukation für Patienten und Eltern, Reduktion von krankheitsspezifischen Emotionen und Kognitionen, Förderung von Selbstwirksamkeitsprozessen, Einbezug sozialer Interaktionspartner, Ressourcenorientierung, Unterstützung durch Selbsthilfe, individuell angepasster Transitionsprozess.

Purpose: To analyze circulating immune cells in patients with anterior uveitis (AU) associated to axial spondyloarthritis (SpA), or juvenile idiopathic arthritis (JIA). Methods: Venous blood samples were collected from healthy controls (n = 16), and either SpA (n = 19) or JIA (n = 23) patients with associated anterior uveitis (AU) during active flare, or after ≥3 months of inactivity. Frequencies of CD56+, MHC-I+, and S100A9+ monocytes, CCR7+ dendritic cells, CD56+dim natural killer (NK) cells and CD3+CD56bright T-cells were analyzed via flow cytometry. Serum S100A8/A9 levels were determined via ELISA. Results: SpA patients showed a reduced frequency of CD56+dim NK cells during uveitis activity, a constitutively activated monocyte phenotype, and elevated S100A8/A9 serum levels. In contrast, JIAU patients showed elevated frequencies of CD56+ monocytes and CCR7+ DC. Conclusion: Phenotype of peripheral immune cells differ between patients, probably contributing to different courses of acute onset AU in SpA and insidious onset AU in JIAU patients. Abbreviations: AU: anterior uveitis, AR: arthritis, JIA: juvenile idiopathic arthritis, SpA: axial spondyloarthritis

Physikalische Therapieverfahren werden neben der medikamentösen, physiotherapeutischen und ergotherapeutischen Behandlung bei entzündlich rheumatischen Erkrankungen und nichtentzündlichen Symptomen des Bewegungsapparats im Kindes- und Jugendalter differenziert eingesetzt zur Entzündungshemmung, Bewegungserweiterung und Schmerzbehandlung. Abhängig von der Symptomatik und den Therapiezielen haben Hydrotherapie, Thermotherapie, Kryotherapie, Elektrotherapie, Phonophorese, Massagen und Lymphdrainage im Rahmen multimodaler Therapiekonzepte einen festen Stellenwert zur Behandlung entzündlicher Prozesse an Gelenken und Enthesen sowie bei chronischen Schmerzerkrankungen des Bewegungssystems. Die physikalischen Therapien sind gut verträglich, weitgehend nebenwirkungsfrei und adaptierbar an das Alter des Patienten. Sie werden abhängig von Intensität und Stadium der Erkrankung, Pathologie der entzündeten Gelenke, dem Krankheitsverlauf und Therapieerfolg individuell angewandt.

ZusammenfassungSchmerzhafte Bewegungseinschränkungen und Gelenkschwellungen, der Nachweis von entzündlichen Veränderungen in der Sonografie oder Kernspintomografie sowie unauffällige laborchemische Untersuchungen sind typische Befunde der juvenilen idiopathischen Arthritis. Allerdings müssen in der differenzialdiagnostischen Abklärung von Arthropathien auch sehr seltene, nicht entzündliche hereditäre Skelettdysplasien in Betracht gezogen werden. Wir berichten über 3 Patienten aus 2 Familien mit einer multiplen epiphysären Dysplasie Typ 4 (MED4). Zwei der Patienten wurden unter dem Verdacht auf ein primär entzündliches Geschehen zunächst antiinflammatorisch behandelt. Die entzündlichen Veränderungen stellten sich jedoch als sekundär, infolge einer bereits fortgeschrittenen Osteoarthrose, heraus. Exemplarisch werden weitere, primär nicht entzündliche Skelettdysplasien vorgestellt, welche sich im Kindes- und Jugendalter manifestieren und mit einem initial normalen Längenwachstum, unauffälligen Körperproportionen, einer unauffälligen Facies sowie einer normalen kognitiven Entwicklung einhergehen.

OBJECTIVE:To analyze the reported association of IL1RN polymorphisms with response to interleukin-1 (IL-1) blockade in a German cohort of patients with systemic juvenile idiopathic arthritis (JIA), and to assess the impact of other factors on treatment response.METHODS:Sixty-one patients with systemic JIA who had received IL-1 blockade were identified within the German Autoinflammatory Disease registry DNA biobank. Response to IL-1 blockade was assessed according to 1) the clinical response (initially at least a transient response or good response compared to a poor response), 2) switch (or no switch) to anti-IL-6 receptor therapy following IL-1 blockade, 3) achievement of clinically inactive disease within 6 months of IL-1 blockade, 4) improvement in disease activity measured using the modified Juvenile Arthritis Disease Activity Score, and 5) achievement of a glucocorticoid-free state. In addition, basic demographic data, key features of the disease course, laboratory data, and IL1RN single-nucleotide polymorphisms (SNPs) were assessed.RESULTS:Six of 7 IL1RN SNPs reported to be associated with response to anakinra therapy were analyzed. These 6 IL1RN SNPs were inherited as haplotypes. An association of IL1RN haplotypes and SNPs with response to IL-1 blockade could not be confirmed in this cohort of patients with systemic JIA. Patients who received tocilizumab following IL-1 blockade had a longer duration from disease onset to diagnosis than those who did not receive tocilizumab (median 0.27 years versus 0.08 years).CONCLUSION:The results of this study could not confirm an impact of IL1RN SNPs on response to IL-1 blockade therapy with either anakinra or canakinumab in a cohort of patients with systemic JIA. However, a longer time frame from disease onset to diagnosis was associated with poorer long-term treatment response, thereby supporting the "window of opportunity" hypothesis that suggests improved long-term treatment response with shorter time from disease onset to diagnosis (and treatment).

Background: At present, etanercept represents the most commonly prescribed biologic agent for juvenile idiopathic arthritis (JIA) treatment. Children and adolescents with JIA are often treated with etanercept over long periods, sometimes even into adulthood. The objectives of this analysis were to determine the long-term safety of etanercept compared to a biologic-naïve cohort, and to assess the long-term treatment response upon continuous etanercept exposure using data from the German biologics registry (BiKeR). Methods: JIA patients newly exposed to etanercept were documented in the BiKeR registry from January 2001 till March 2019, and baseline characteristics, effectiveness, as well as safety parameters were analysed. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), JADAS-defined minimal disease activity and remission, JIA-American College of Rheumatology (ACR) improvement criteria, as well as ACR-inactive disease definition. Safety assessments were based on adverse events (AE) reports. Results: 2725 new etanercept users with a diagnosis of JIA were registered. Of these, etanercept was received as a first-line biologic by 95.8% and as monotherapy without concomitant methotrexate by 31.5%. After nine years on continuous treatment, 68.1% of patients presented minimal disease activity, 43.1% JADAS-defined remission on drug and 36.6% ACR-inactive disease. JIA-ACR30/50/70/90 response rates were still 82/79/71/54% after 9 years of treatment. Overall, 2053 AEs (34.3/100PY), including 226 serious AEs (SAE, 3.8/100PY), were observed upon etanercept, compared to 1345 AEs [35.6/100PY; p=0.3] and 52 SAEs (1.4/100PY; p=0.0001) in the biologic-naïve cohort. Respective exposure-adjusted rates for etanercept and biologic-naïve patients were 0.9/100PY and 0.2/100PY (p=0.0001) for serious infections, 0.4/100PY and 0.1/100PY (p=0.01) for zoster reactivation, 0.3/100PY and 0.03/100PY (p=0.015) for inflammatory bowel disease, 1.9/100PY and 1.4/100PY (p=0.09) for uveitis. Three and two malignancies were documented in the etanercept and biologic-naïve groups, as well as three and one deaths, respectively. Conclusions: No new safety signal was observed, especially no increased risk for malignancies or autoimmune disorders other than inflammatory bowel disease. However, SAEs and serious infections, though infrequent, were more often reported on etanercept than in biologic-naïve patients. In addition, etanercept demonstrated a long-term maintenance of clinical benefits up to nine years of continuous treatment. Keywords: Juvenile idiopathic arthritis, JIA-treatment, etanercept, TNF-inhibitors, biologics registry, drug surveillance

Background Patients with juvenile idiopathic arthritis (JIA) may have a different body composition associated with reduced muscle mass and increased fat mass [1]. They display decreased physical fitness, perform less strenuous physical activities, and spend more time sleeping than do healthy children. A lower level of physical activity is associated with deconditioning and functional deterioration, favoring an inactive lifestyle. The risk of overweight might be further increased by the glucocorticoid treatment. Objectives Since obesity can increase inflammatory processes, cause early atherosclerotic changes and promote metabolic disorders, the objectives were a) to determine the prevalence of overweight and obesity in children and adolescents with JIA, and b) to examine the association between overweight and health-related parameters in this population. Methods A cross-sectional analysis of physicians’ recorded body weights and heights of patients with JIA enrolled in the NPRD in the year 2016 was performed. Overweight was defined as BMI >90th sex- and age-specific percentile and obesity as BMI >97th percentile. For comparison with data from the general German population [2], patients aged 3 to 17 years were considered. A linear regression model was used to explore the association between overweight and both clinical as well as self-reported outcomes. Results In total, data from 6.860 children and adolescents with JIA (age 11.5 ± 4 years, disease duration 4.6 ± 3.6 years, 67% girls, 39% persistent oligoarthritis) were analyzed. Overweight was found in 14% (including 6% obesity) of JIA cases. Comparative data from the German general population report an overweight prevalence of 15% (including 6% obesity). In contrast to the general population, overweight rates in JIA differed between girls and boys (girls 14% vs. boys 16%, p<0.05). Patients with psoriatic arthritis (20%) and systemic JIA (18%) showed the highest overweight rates. In multivariate analyses, age (OR 1.06; 95%CI: 1.04-1.09), male sex (OR 1.21; 95%CI: 1.01-1.44), functional limitations (OR 1.29; 95%CI: 1.04-1.59), as well as therapy with biological DMARDs (OR 1.48; 95%CI: 1.22-1.80) and systemic glucocorticoids (OR 1.40; 95%CI: 1.14-1.71) were significantly associated with overweight. Conclusion The prevalence of overweight and obesity in young patients with JIA is similar to that of children and adolescents in the general population. The overweight rate increases with age and is strongly associated with functional restrictions and treatment with glucocorticoids. The role of overweight in the long-term outcome of JIA is an issue that still needs to be addressed. References [1] Grönlund MM, et al. Juvenile idiopathic arthritis patients with low inflammatory activity have increased adiposity. Scand J Rheumatol 2014;43:488–92. [2] Schienkiewitz A, et al. Übergewicht und Adipositas im Kindes- und Jugendalter in Deutschland. Journal of Health Monitoring 2018; 3:16–23. Acknowledgement The National Paediatric Rheumatological Database has been funded by the German Children Arthritis Foundation (Deutsche Kinder-Rheumastiftung), AbbVie, Pfizer and Chugai. Disclosure of Interests Florian Milatz: None declared, Jens Klotsche: None declared, Martina Niewerth: None declared, Nils Geisemeyer: None declared, Jana Hörstermann: None declared, Gerd Ganser: None declared, Ivan Foeldvari Consultant for: Chugai, Novartis, Angelika Thon: None declared, Rainer Berendes: None declared, Markus Hufnagel: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Kirsten Minden Consultant for: AbbVie

Background Since 2011 Tocilizumab is approved for systemic juvenile idiopathic arthritis (JIA) and since 2013 for polyarticular JIA Objectives To describe efficacy and safety of Tocilizumab in clinical practice in polyarticular (pJIA) and systemic JIA (sJIA) patients using the German Biologics registry (BiKeR) Methods Baseline demographics and disease activity parameters have been documented. Efficacy was determined using the JADAS10 prospectively. Safety assessments were based on adverse events reports (AE) processed according to MedDRA Results Until October 1, 2018, 345 JIA patients treated with Tocilizumab were registered, representing 635 patient-years (PY) of observation. The cohort treated with Tocilizumab had experienced disease duration of 5.5+/-4.3 years (mean+/-SD) for sJIA and 5.9+/-4.1 years for pJIA. sJIA/pJIA patients received pretreatment with MTX 72%/96%, Anakinra 23%/1%, Adalimumab 4%/60%, Etanercept 30%/69%, Canakinumab 2%/0%. Concomitantly, sJIA/pJIA patients received NSAIDs 64%/57%, systemic steroids 72%/35%, MTX 55%/54%, other DMARDS 4%/8%. At last follow-up, 63%/60%/51%/43% of sJIA and 56%/49%/40%/30% of pJIA patients reached JIAACR30/50/70/90 criteria. After 2 years of treatment JADAS remission was reached by 50%/43% and JADAS minimal disease activity by 67%/67%. 586 AE were reported during exposure plus 90 days of observation. The rate was significantly higher in sJIA (104/100PY [95% CI 92-119]) than in pJIA patients (79 [79-90]; RR 1.3; p=0.003). 75 qualified as serious AE (SAE) with a higher rate in sJIA (22[16-29] vs. 8 [5-12], RR 2.6; p<0.001). The most frequent AE in the sJIA/pJIA cohort were grouped in the MedDRA SOC infections and infestations (n=92/76). Compared to pJIA, rates were significantly higher in sJIA patients for blood and lymphatic (RR 2.4; p=0.019), immune system (RR 2.6; p=0.04), infections & infestations (RR 1.7, p<0,001) and nervous system disorder (RR 2.6, p=0.012) and lower for general and administration site (RR 0.4; p=0.023). 169 patients (49%) discontinued treatment, 17% due to remission, 22% due to lack of efficacy and 9% because of intolerance. Conclusion The analysis adds to the established safety profile of tocilizumab in paediatric patients with systemic & polyJIA. Differences were noted between pJIA and sJIA cohorts, the latter with higher rates of total number of adverse events, serious AE, infections and cytopenias, probably due to higher doses or shorter application intervals. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients. References [1] Horneff G, et al. Arthritis Res Ther. 2016Nov24;18(1):272 Acknowledgement BIKER and the documentation of the treatment with biologics is partially sponsored by Chugai and Roche, Germany Disclosure of Interests Ariane Klein: None declared, Gerd Ganser: None declared, Ralf Trauzeddel: None declared, Kisten Minden Grant/research support from: Pfizer, Abbvie, Christoph Rietschel: None declared, Jasmin Kuemmerle-Deschner Grant/research support from: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Consultant for: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Speakers bureau: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Gerd Horneff: None declared

BackgroundEtanercept is the most frequently used biologic drug in patients with JIA. Children and adolescents with JIA are treated with etanercept often over long periods of time, sometimes even into adulthood. The knowledge about its long-term safety, especially with regard to the occurrence of new-onset immune-mediated diseases and malignancies, is still limited.ObjectivesTo investigate the exposure-adjusted rates of adverse events (AE) and serious AE (SAE) in patients with JIA with long-term use of etanercept.MethodsPatients with JIA who were enrolled in the German biologic register BiKeR and were born before 30.05.2000 (at least 18 years of age at this date) were considered for this analysis. The follow-up register JuMBO ensures the long-term follow-up into adulthood. An AE or SAE was attributed to etanercept when the treatment was either ongoing or terminated in less than 3 month prior to the event. The incidence of malignancies was estimated in patients who were ever exposed to etanercept with at least one dose.ResultsOf 4546 patients who were currently enrolled in BiKeR a total of 2584 JIA patients were eligible for the JuMBO register (>18 years). Among those, 1765 (68%) were ever exposed to etanercept and observed for a mean of 6.8±4.9 years (including 1101 into adulthood). The majority of them had polyarthritis (35%), followed by enthesitis-related arthritis (20%) and extended oligoarthritis (17%). The patients were exposed to etanercept for a total of 4.2 years (mean, 6,726 exposure years, EY); 518 patients were continuously treated with etanercept for at least 5 years (4,534 EY). In total, 124 autoimmune events (1.84/100EY) and 7 other immune disorders (0.10/100EY) were reported in 102 (5.8%) and 7 (0.4%) patients with onset on average 10.2 years after JIA onset, and 6.8 years after start with etanercept, respectively. The number of selected immune-mediated events and the exposure-adjusted rates are given in the table. In addition, 11 malignancies (0.10 events/100 person-years) were reported in patients ever exposed to etanercept. Among those (mean age at onset 20.3 years), 4 malignancies were reported in childhood and 7 in young adulthood. Three patients were also exposed to other biologics before the incidence of malignancy. The malignancies occurred on average 12.1 years after JIA onset, 10.4 years after start with a first DMARD and 7.5 years after first exposure to etanercept.ConclusionThis is the first long-term large safety study in prospectively followed JIA patients with focus on new-onset immune-mediated diseases and malignancies in etanercept. The study also highlights that it is important to prospectively collect data on adverse events under treatment with biologics in JIA, in particular with respect to the risk of malignancies in young adulthood.Disclosure of InterestsJens Klotsche: None declared, Ariane Klein: None declared, Martina Niewerth: None declared, Gerd Ganser: None declared, Peer Aries: None declared, Marisa Walther: None declared, Peter Haas Grant/research support from: Pfizer, Gernot Keyßer: None declared, Gerd Horneff: None declared, Kirsten Minden Consultant for: AbbVie

Background Canakinumab is approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) older than 2 years. Objectives The aim of the German Biologics Registry (BiKeR) is the surveillance of JIA patients exposed to biologics. Methods Baseline demographics and disease activity parameters were documented. Efficacy was determined using the JADAS and the proposed criteria for inactive disease on medication. Safety assessments were based on reports of adverse events (AE). All reports have been coded according to MedDRA ®. Results 48 sJIA patients with 82.5 patient-years (PY) of exposure to Canakinumab were recorded in the German BiKeR registry. The total observation time (from date of first dose until last follow-up, censored, if another biologic was started) was calculated with 109.9 PY. The cohort treated with Canakinumab had experienced long disease duration of 2.9+/-3.8 years (mean +/- SD). 21 (44%) were pre-treated with methotrexate, 10 (21%) with Etanercept, 3 (6%) with Adalimumab, 18 (38%) with Anakinra and 19 (40%) with Tocilizumab. Concomitantly, 9 (18.8%) received methotrexate, 22 (45.8%) NSAIDs and 23 (48%) systemic corticosteroids. At last follow up upon treatment, 48%/44%/42%/38% of patients reached PedACR30/50/70/90 improvement. 8 patients (16.7%) had inactive disease according to the Wallace criteria. The median (IQR1-IQR3) JADAS10 score decreased from 12.6 (6.2-15.8) at baseline to 0.5 (0.0-2.8). During ongoing treatment, approximately 82% of patients achieved a JADAS defined minimal disease activity; while 64% reached a JADAS defined remission at last follow-up. 125 adverse events (AE) were recorded (114 events/100PY [95% CI 96-136]). Of these, 22 qualified as serious adverse events (SAE) (20/100PY [13-30]). 100 AEs were observed during exposure or up to 90 days follow up after the last exposure to Canakinumab (121/100PY [99-147]). 19 qualified as SAE (23/100PY [15-36]). Adverse Events of Special Interest were serious and medically important infection (n=4), cytopenia (n=4), macrophage activation syndrome (n=3). There was no opportunistic infection, intestinal perforation, anaphylaxis or other hypersensitivity, thrombotic event, evolving autoimmune disease, cardiac or cerebral event, bleeding, malignancy, or death. A total of 38 patients (79%) discontinued treatment, 8 (17%) due to lack or efficacy, 16 (33%) due to remission and 2 (4%) because of intolerance. Conclusion The current analysis adds to the established safety profile of Canakinumab and demonstrates that safety was comparable and consistent with the overall AE profile of Canakinumab in paediatric patients. MAS occurred in three sJIA patients and might be a JIA-associated feature. Infections were the most frequent AE, but only two serious infections were reported. No new safety signals specific to the paediatric population were identified for Canakinumab; the risk profile of Canakinumab remains positive for the approved paediatric indication sJIA. References [1] Horneff G, Klein A, Klotsche J, Minden K, Huppertz HI, Weller-Heinemann F, Kuemmerle-Deschner J, Haas JP, Hospach A. Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab. Arthritis Res Ther. 2016Nov24;18(1):272 Acknowledgement The authors acknowledge all contributors to BIKER, patients, parents and study staff Disclosure of Interests Gerd Horneff: None declared, Eggert Lilienthal: None declared, Ralf Trauzeddel: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Frank Dressler Paid instructor for: Abbvie, Pfizer, Novartis, Michaela Sailer-Hoeck: None declared, Gerd Ganser: None declared, Frank Weller-Heinemann: None declared, Georg Heubner: None declared, Andreas Urban: None declared, Michael Rühlmann: None declared, Christoph Rietschel: None declared, Markus Hufnagel: None declared, Wolfgang Emminger: None declared, Ariane Klein: None declared

Background Anakinra (ANA) is recommended for treatment of systemic juvenile idiopathic arthritis (sJIA) and has recently received EMA approval. Objectives To describe safety and effectiveness of ANA in clinical practice in sJIA patients documented in the German Biologics registry (BiKeR). Methods Demographic and clinical parameters of the patients were recorded at BiKeR enrollment, ANA effectiveness was evaluated by half-yearly evaluation of disease activity using JADAS-10. Safety assessments were based on MedDRA-coded adverse events (AE) reports. Results Until December 1 2018, 50 sJIA patients treated with ANA were registered, representing 113.4 patient-years (PY) of observation, with 10 patients (20%) receiving ANA for at least 4 years. The cohort treated with ANA had experienced a prior disease duration of 3.5+/-3.8 years (mean+/-SD). Most sJIA patients treated with ANA received pretreatment: 35 patients (70%) were pretreated with at least one other biologic, mostly etanercept (n=28), followed by tocilizumab (6) and canakinumab (1). Further pretreatments included methotrexate (MTX, n= 35), ciclosporine A (n=13), azathioprine (n=8) and other DMARDs at lower frequency. 39 patients had received corticosteroids. Concomitant treatment consisted of NSAIDs (n=20), systemic steroids (n=35), MTX (n=29) and other DMARDs (n=8). At month 3, JADAS minimal disease activity (MDA)/JADAS remission and inactive disease according to Wallace [1] were observed in 42%/37%and 47%, respectively. After one year of treatment, the rates were 62%/45% and 56%, respectively (Figure 1). Conclusion The current analysis adds to the established safety profile of Anakinra and demonstrates that in ANA treated patients with sJIA the rate of SAEs was comparable and consistent with the overall AE profile of ANA in pediatric patients. Hospitalisation was the usual reason for classification as serious AE. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients. Disclosure of Interests Ariane Klein: None declared, Veronika Ntam Atemnkeng: None declared, Frank Dressler Paid instructor for: Abbvie, Pfizer, Novartis, Ivan Foeldvari Consultant for: Chugai, Novartis, Rolf Michael Küster: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Gerd Ganser: None declared, Kirsten Minden Consultant for: AbbVie, Dirk Foell Grant/research support from: not specified, Consultant for: not specified, Speakers bureau: not specified, Frank Weller-Heinemann: None declared, Jasmin Kuemmerle-Deschner Grant/research support from: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Consultant for: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Speakers bureau: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Boris Huegle: None declared, Christoph Rietschel: None declared, Eggert Lilienthal: None declared, Gerd Horneff: None declared

Background Since 2000, Etanercept is approved for polyarticular juvenile idiopathic arthritis (JIA). Subsequently, approval has been extended to additional JIA categories. Objectives To describe efficacy and safety of Etanercept in clinical practice in JIA patients in comparison to a biologic-naïve JIA cohort using the German Biologics registry (BiKeR). Methods Baseline demographics and disease activity parameters were documented. Efficacy was determined using the JADAS10. Safety assessments were based on adverse events reports (AE) processed according to MedDRA. Results Until October 1, 2018, 2645 JIA patients treated with Etanercept were registered, representing 5820 patient-years (PY) of exposure. The total observation time (from date of first dose until last follow-up, censored, if another biologic was started) was calculated as 8080 PY. In general, the cohort treated with Etanercept had experienced disease duration of 4.2+/-3.7 years (mean+/-SD). 2303 patients (87%) were pretreated with methotrexate, 100 with alternative biologics. Concomitantly, 1822 patients (69%) received methotrexate, 2098 (79%) NSAIDs, 949 (36%) systemic corticosteroids as well as further drugs in lower numbers. In the control cohort, 1517 biologic naive JIA patients started methotrexate. At last follow-up, 68%/62%/50%/34% of patients reached JIAACR30/50/70/90 criteria. The median (IQR1-3) JADAS10 score decreased from 15.0 (10-20.4) at baseline to 3.5 (0.7-10.1). 60% of patients achieved a JADAS defined minimal disease activity, 40% reached a JADAS remission. 1924 AE were observed (33.1/100PY [95% CI 31.6-34.6]). 221qualified as SAE (3.8/100PY [3.3-4.3]). These figures were compared to 1292 AE reported during 3714PY in the control cohort (34.8/year [32.9-36.8]) and 52 SAE (1.4/100PY [1.1-1.8]). The most frequent SAE in the Etanercept cohort were grouped in the MedDRA SOC infections and infestations (n=54) followed by musculoskeletal and connective tissue disorders (n=27), eye disorders (n=21), gastrointestinal disorders (n=17) and nervous system disorders (n=15). There were 5 deaths. Serious infections were of bacterial and viral origin and mostly occurred once only. Adverse events of special interest were uveitis (n=109), H. zoster (n=24), chronic inflammatory bowel disease (n=19), pregnancies (n=4), depression (n= 11), malignancies (n=8), demyelination (n=2). Adverse Events of Special Interest (AESI) were in the MTX–cohort uveitis (n=52), H. zoster (n=4), chronic inflammatory bowel disease (n=1), depression (n= 2), malignancies (n=4). A total of 1606 patients (60.7%) discontinued treatment. Of these 638 (39.7%) discontinued due to remission, 565 (35.2%) due to lack of efficacy and 188 (11.7%) because of intolerance. Conclusion The current analysis adds to the established safety profile of Etanercept and demonstrates that the rate of SAEs is comparable and consistent with the overall AE profile in paediatric patients. As expected, infections are the most frequent SAE. Uveitis is likely associated with JIA. Of notice, few patients developed a chronic inflammatory bowel disease and some a malignancy. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients. References [1] Geikowski T, Becker I, Horneff G; German BIKER Registry Collaborative Study Group. Predictors of response to etanercept in polyarticular-course juvenile idiopathic arthritis. Rheumatology (Oxford). 2014 Jul;53(7):1245-9 Acknowledgement The authors acknowledge the support of the patients, parents and all contributors Disclosure of Interests Ariane Klein: None declared, Gerd Ganser: None declared, Michael Rühlmann: None declared, Frank Dressler Paid instructor for: Abbvie, Pfizer, Novartis, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Kirsten Minden Consultant for: AbbVie, Ralf Trauzeddel: None declared, Boris Huegle: None declared, Sonja Mrusek: None declared, Ivan Foeldvari Consultant for: Chugai, Novartis, Jasmin Kuemmerle-Deschner Grant/research support from: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Consultant for: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Speakers bureau: Jasmin Kuemmerle-Deschner is an employee of University of Tuebingen, Germany, and received consultants/speakers fees from Novartis and SOBI pharmaceuticals and grant support from SOBI and Novartis., Frank Weller-Heinemann: None declared, Andreas Urban: None declared, Gerd Horneff: None declared

The Second author's name was incorrectly published in the original article. The correct name is Hartwig Wilhelm Lehmann.

Background Since 2008, Adalimumab is approved for polyarticular juvenile idiopathic arthritis (JIA) and approval has been extended to other JIA categories and for uveitis. Objectives To evaluate efficacy and safety of Adalimumab in clinical practice in JIA patients in comparison to a biologic-naïve JIA cohort using the German Biologics registry (BiKeR). Methods Baseline demographics and disease activity parameters have been documented. Efficacy was determined using the JADAS10. Safety assessments were based on adverse events (AE) reports processed according to MedDRA. Results Until October 1, 2018, 951 JIA patients treated with Adalimumab were registered in BiKeR, representing 1519 patient-years (PY) of exposure. The total observation time (from date of first dose until last follow-up, censored, if another biologic was started) was calculated with 1709 PY. At baseline, the cohort treated with Adalimumab had experienced disease with a disease duration of 5.4+/-3.9 years (mean+/-SD). 849 patients (89.3%) were pretreated with methotrexate, 525 (54.2%) with Etanercept. Concomitantly, 584 (61.4%) received methotrexate, 529 (55.6%) NSAIDs and 255 (26.8%) systemic corticosteroids. In the control cohort, 1517 biologic naive JIA patients started methotrexate. Upon treatment, the median (IQR1-3) JADAS10 score decreased from 9.8 (4.7-15.5) at baseline to 3.9 (0.9-9.7) at the last follow-up. With respect to patients with ongoing treatment, approximately 43% achieved a JADAS defined minimal disease activity while 25% reached a JADAS defined remission at last follow-up. 904 AE have been observed during exposure or up to 90 days follow-up (58.4/100 exposure years (EY) [95% CI 54.7-62.3]). 66 qualified as serious AE (SAE) (4.3/100 EY [3.3-5.4]). These figures were compared to 1294 AE reported in the control cohort (34.8/year [32.9-36.8]) and 52 SAE (1.4/100 EY [1.1-1.8]). Adverse events of special interest were serious/medically important infection (n=33), opportunistic infection (n=6, all H. zoster), malignancy (n=2), anaphylaxis/hypersensitivities (n=3), thrombotic disorders (n=2), autoimmune diseases (n=91, including 12 cases with psoriasis and 53 reports of uveitis), bleeding (n=3), cytopenias (n=4), pregnancies (n=2). Macrophage activation syndrome, demyelination, cardiac or cerebral infarction, or death were not observed. However, 2 malignancies were reported in patients who had ever been exposed to Adalimumab before. Both events were judged as unrelated. A total of 449 patients (48.5%) discontinued Adalimumab, 188 (19.8%) due to lack of efficacy, 111 (11.7%) due to remission and 78 (8.2%) because of intolerance. Conclusion The current analysis adds to the established safety profile of Adalimumab and demonstrates that the rate of SAEs was comparable and consistent with the overall AE profile in paediatric patients. As expected, infections were the most frequent SAE. Uveitis, as well as psoriasis, are likely associated with JIA. Of notice, only one patient developed a chronic inflammatory bowel disease. No new safety signals specific to the paediatric population were identified in this large cohort of JIA patients. References [1] Klein A, Becker I, Minden K, Foeldvari I, Haas JP, Horneff G. Adalimumab versus adalimumab and methotrexate for the treatment of juvenile idiopathic arthritis: long-term data from the German BIKER registry. Scand J Rheumatol. 2018Nov9:1-10. Acknowledgement The authors acknowledge all patients, parents and ciontributors to the BIKER registry and Abbvie, Germany, for financial Support for parts of BIKER. Disclosure of Interests Gerd Horneff: None declared, Kisten Minden Grant/research support from: Pfizer, Abbvie, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Ivan Foeldvari Consultant for: Chugai, Novartis, Peter Haas Grant/research support from: Pfizer, Angelika Thon: None declared, Betina Rogalski <: None declared, Gerd Ganser: None declared, Frank Weller-Heinemann: None declared, Andreas Urban: None declared, Markus Hufnagel: None declared, Prasad Oommen: None declared, Ariane Klein: None declared

Background Long-term surveillance of biologics drugs is particularly important in paediatric patients (pts) Objectives To evaluate long-term rates of serious adverse events (AE) and AEs of special interest (AESI) in clinical practice in pts with juvenile idiopathic arthritis (JIA) Methods Safety data from pts registered in the BIKER registry were analysed. Rates of 25 AESI were analysed from first dose through 70 days after last dose and compared by Wald test Results A total of 3975 courses of biologics with a total exposure of 7592 PY were identified with Etanercept (5376PY) followed by Adalimumab (1334PY), Tocilizumab (435PY), Abatacept (109PY), Infliximab (99PY), Anakinra (96 PY), Canakinumab (71PY) and Golimumab (67PY). Differences in JIA category distribution and concomitant treatment were noted. A total of 3586 AE (47.2/100PY), 461 (6.1) SAE and 629 (8.3) AESI were reported. The most common AESI were uveitis (194 (2.6)) followed by medically important infections (155 (2.0)), cytopenias (62 (0.8)), hepatic events 39 (0.5), anaphylaxis (28 (0.4))), other autoimmunopathies (25 (0.3)), chronic inflammatory bowel disease (23 (0.3)), depression (17 (0.2)), macrophage activation syndrome (12 (0.2)), malignancies (8 (0.1)) and pregnancies (8 (0.1)). There were marked differences in the rate of AESI with different biologics. Uveitis were most common in TNF-antibody treated cohorts, infections upon GOL, TOC, ANA, cytopenias upon TOC, CAN, hepatic events upon TOC, anaphylaxis upon INF, TOC, CED upon ETA, INF (table 1). One case of latent TB but no further opportunistic infections were reported. There was a single death due to sepsis. [KM1]Vorn 2481 [KM2]Vorn 67? Conclusions Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for long term treatment of children. Overall, tolerance is acceptable. Differences between several biologics were noted and should be considered in daily patient care Disclosure of Interest None declared

Achieving the best possible health-related quality of life (HRQoL) for a patient is an important treatment goal in juvenile idiopathic arthritis (JIA). We investigated the 36-month trajectories of HRQoL in children with JIA compared with healthy peers and identified the predictors of an unfavorable HRQoL.