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The aim of our study was to describe the distinct features of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) patients and to identify risk factors for its development.Data from the German biologics in paediatric rheumatology registry (Biologika in der Kinderrheumatologie (BiKeR)) collected between 2001 to 2021 were analysed retrospectively.In 5009 JIA patients, 28 developed confirmed IBD before the age of 18 years: 23 (82.1%) with Crohn's disease (CD), 4 (14.3%) with ulcerative colitis (UC) and 1 (3.6%) with IBD-unclassified. The incident rate of IBD during 20 years of observation was 0.56% (0.46% for CD, 0.08% for UC, 0.02% for IBD-U), of whom 20.3% were HLA-B27 positive, 25% had enthesitis-related arthritis and 14.3% psoriatic arthritis. Within 90 days before IBD diagnosis, 82.1% (n=23) received treatment with etanercept (ETA), 39.3% (n=11) NSAID, 17.9% (n=5) systemic corticosteroids, 8 (28.6%) methotrexate (MTX), 14.3% (n=4) sulfasalazine, 10.7% (n=3) leflunomide, and 3.6% (n=1) adalimumab and infliximab, respectively. The incidence of IBD was lower in patients treated with MTX, but higher in patients treated with ETA except if ETA was combined with MTX. Also in patients on leflunomide or sulfasalazine, the IBD incidence was higher.In our JIA cohort, an increased IBD incidence is observed compared to the general population, and the ratio of CD to UC is markedly higher hinting at a distinct phenotype of IBD. Pre-treatment with MTX seems to be protective. Treatment with ETA does not prevent IBD development and JIA patients treated with leflunomide and sulfasalazine may be at an increased risk for IBD development.An infographic is available for this article at: http://links.lww.com/MPG/C985.

BackgroundTreatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy.MethodsIn this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to ResultsA total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; pConclusionsSecukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis.Trial registration numberNCT03031782.

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

To review the effectiveness of secukinumab (SEC) in patients with juvenile idiopathic enthesitis related arthritis (ERA), who had partial or no response on anti-TNF therapy.We conducted a retrospective monocentric chart review of patients with ERA, who were treated with SEC, until March 15th 2019. We used the JADAS10 and the Juvenile Spondyloarthritis Disease Activity Index (jspADA) to evaluate response. We analysed the onset of AE and SAE.We analysed 17 patients with ERA. The mean age at the start of the treatment was 19.5 years (SD 4.9, range 13-34 years, median 18.2). The mean disease duration was 6.3 years (SD 3.3, range 2-12 years). The patients received in average 1.9 (SD1.0) different anti-TNF'́s before switching to SEC. SEC was applied at the start of the treatment with 150 mg per dose (n=13, 76.5%) and 300 mg per dose (n=4, 23.5%). The dose of 150 mg was increased in 11 patients (85% of 13) after baseline. The mean follow-up of patients was 18.2 months (SD 7.2) accounting to 25.8 years under exposure to SEC. The jspADA (mean change of -1.3; p0.001; 95%CI: -1.9 to -0.7) and JADAS10 (mean change of -2.4; p=0.021; 95%CI: -4.5 to -0.4) signi cantly improved between baseline and the 24-month follow-up. There was no serious adverse event observed.In our anti-TNF non-responder patients SEC showed good effectiveness. The 150 mg dose seems to be insufficient in anti-TNF non-responder patients and most patients had to be escalated to the 300 mg/dose.

Objectives CLIPPER2 was an 8-year, open-label extension of the phase 3b, 2-year CLIPPER study on the safety and efficacy of etanercept in patients with JIA, categorized as extended oligoarticular arthritis (eoJIA), enthesitis-related arthritis (ERA) or PsA. Methods Participants with eoJIA (2–17 years old), ERA or PsA (each 12–17 years old) who received ≥1 etanercept dose (0.8 mg/kg weekly; maximum 50 mg) in CLIPPER could enter CLIPPER2. Primary end point was occurrence of malignancy. Efficacy assessments included proportions achieving JIA ACR 30/50/70/90/100 criteria and ACR inactive disease criteria, and clinical remission (ACR criteria) or Juvenile Arthritis DAS (JADAS) ≤1. Results Overall, 109/127 (86%) CLIPPER participants entered CLIPPER2 [n = 55 eoJIA, n = 31 ERA, n = 23 PsA; 99 (78%) on active treatment]; 84 (66%) completed 120 months’ follow-up [32 (25%) on active treatment]. One malignancy (Hodgkin’s disease in 18-year-old patient with eoJIA treated with methotrexate for 8 years) was reported; there were no cases of active tuberculosis or deaths. Numbers and incidence rates (events per 100 patient-years) of TEAEs (excluding infections/ISRs) decreased from 193 (173.81) in Year 1 to 9 (27.15) in Year 10; TE infections and serious infections also decreased. Over 45% of participants (n = 127) achieved JIA ACR50 responses from Month 2 onwards; 42 (33%) and 34 (27%) participants achieved JADAS and ACR clinical remission, respectively. Conclusions Etanercept treatment up to 10 years was well tolerated, consistent with the known safety profile, with durable response in the participants still on active treatment. The benefit–risk assessment of etanercept in these JIA categories remains favourable. Trial registration ClinicalTrials.gov IDs: CLIPPER (NCT00962741); CLIPPER2 (NCT01421069)

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

Die juvenile systemische Sklerodermie (jSSc) ist eine seltene Erkrankung mit einer Haufigkeit von 3 in 1 Mio. Kindern. Die juvenile systemische Sklerodermie Inzeptionskohorte ( www.juvenile-scleroderma.com ) ist aktuell die groste Kohorte von Patienten mit jSSc. In die Kohorte konnen Patienten eingeschlossen werden, wenn sie die Klassifikationskriterien der Erwachsenenkriterien der ACR/EULAR fur systemische Sklerodermie erfullen, die ersten Non-Raynaud-Symptome im Alter unter 16 zeigen und beim Einschluss in die Kohorte junger als 18 Jahre sind. Die Patienten werden alle 6 Monate mit standardisierter Erfassung evaluiert. Auf dem EULAR-Kongress 2021 wurden 2 Beitrage zu dieser Kohorte prasentiert. Ein Beitrag verglich die Patienten mit diffusem und limitiertem Subtyp, wobei spezifische Unterschiede aufgezeigt werden konnten, aber auch viele Ahnlichkeiten zwischen den Subtypen, verglichen mit erwachsenen Patienten mit systemischer Sklerodermie. In dem anderen Beitrag konnte gezeigt werden, dass Patienten mit Overlap-Zeichen eine deutlich hohere Rate von interstitieller Lungenerkrankung haben, was zuvor nicht erwartet wurde. Die juvenile systemische Sklerodermie Inzeptionskohorte ( www.juvenile-scleroderma.com ) wird laufend erweitert, wobei Patienten kontinuierlich rekrutiert werden. Wir freuen uns uber jeden Patienten, bitte nehmen Sie gerne Kontakt auf, wenn Sie einen Patienten einschliesen mochten.

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Objective To investigate the impact of additionally given MTX on biologic treatment of polyarticular JIA in terms of effectiveness, safety and drug survival. Methods Patients suffering from polyarticular JIA and treated with either monotherapy with a first biologic or a combination of a biologic and MTX were selected from the BIKER registry. The TNF-α inhibitors (TNFi) adalimumab, etanercept and golimumab and the IL-6 inhibitor tocilizumab were considered. Upon a non-randomized study design, we adjusted the different cohorts using propensity score matching to improve comparability. Results A total of 2148 patients entered the analysis, who were treated by either combination therapy (n = 1464) or monotherapy (n = 684). Disease activity declined significantly more in patients upon combination therapy than upon biologic monotherapy. Comparison of adjusted cohorts revealed that patients who received TNFi gained more benefit from additionally given MTX than patients treated with tocilizumab. Median survival time of therapy with biologics was significantly longer upon combination therapy (3.1 years) than with monotherapy (2.7 years), as demonstrated by a Kaplan–Meier analysis (log rank test: P = 0.002). The safety profile was moderately affected by additional MTX due to increased incidence of gastrointestinal and hepatic adverse events. Serious adverse events occurred at an equal rate of 3.6 events per 100 patient-years in both cohorts. Conclusion Additionally given MTX improves the effectiveness of biologic treatment in polyarticular JIA without seriously compromising treatment safety. Especially TNFi benefit from combination, while no improvement in outcome has been observed by combining tocilizumab with MTX.

Objective To evaluate safety and effectiveness of adalimumab (ADA) in polyarticular-course juvenile idiopathic arthritis (JIA) in the STRIVE registry. Methods STRIVE enrolled patients with polyarticular-course JIA into 2 arms based on treatment with methotrexate (MTX) alone or ADA with/without MTX (ADA +/- MTX). Adverse events (AEs) per 100 patient-years of observation time were analyzed by registry arm. Patients who entered the registry within 4 weeks of starting MTX or ADA +/- MTX, defined as new users, were evaluated for change in disease activity assessed by the 27-joint Juvenile Arthritis Disease Activity Score with the C-reactive protein level (JADAS-27(CRP)). Results At the 7-year cutoff date (June 1, 2016), data from 838 patients were available (MTX arm n = 301, ADA +/- MTX arm n = 537). The most common AEs were nausea (10.3%), sinusitis (4.7%), and vomiting (4.3%) in the MTX arm and arthritis (3.9%), upper respiratory tract infection (3.5%), sinusitis, tonsillitis, and injection site pain (3.0% each) in the ADA +/- MTX arm. Rates of serious infection were 1.5 events/100 patient-years in the MTX arm and 2.0 events/100 patient-years in the ADA +/- MTX arm. AE and serious AE rates were similar in patients receiving ADA with versus without MTX. No deaths or malignancies were reported. New users in the ADA +/- MTX arm showed a trend toward lower mean JADAS-27(CRP)compared with new users in the MTX arm in the first year of STRIVE. Conclusion The STRIVE registry 7-year interim results support the idea that ADA +/- MTX is well tolerated by most children. Registry median ADA exposure was 2.47 (interquartile range 1.0-3.6) years, with 42% of patients continuing ADA at the 7-year cutoff date.

To standardly assess and describe nailfold videocapillaroscopy (NVC) assessment in children and adolescents with juvenile rheumatic and musculoskeletal diseases (jRMD) versus healthy controls (HC).In consecutive jRMD children and matched HC from 13 centres worldwide, 16 NVC images per patient were acquired locally and read centrally per international consensus standard evaluation of the EULAR Study Group on Microcirculation in Rheumatic Diseases. 95 patients with juvenile idiopathic arthritis (JIA), 22 with dermatomyositis (JDM), 20 with systemic lupus erythematosus (cSLE), 13 with systemic sclerosis (jSSc), 21 with localized scleroderma (lSc), 18 with mixed connective tissue disease (MCTD) and 20 with primary Raynaud's phenomenon (PRP) were included. NVC differences between juvenile subgroups and HC were calculated through multivariable regression analysis.A total number of 6474 images were assessed from 413 subjects (mean age 12.1-years, 70.9% female). The quantitative NVC-characteristics were significantly lower (↓) or higher (↑) in the following subgroups compared to HC: For density: ↓ in jSSc, JDM, MCTD, cSLE and lSc; For dilations: ↑ in jSSc, MCTD and JDM; For abnormal shapes: ↑ JDM and MCTD; For haemorrhages: ↑ in jSSc, MCTD, JDM and cSLE. The qualitative NVC-assessment of JIA, lSc and PRP did not differ from HC, whereas the cSLE and jSSc, MCTD, JDM, cSLE subgroups showed more non-specific and scleroderma patterns respectively.This analysis resulted from a pioneering registry of NVC in jRMD. The NVC-assessment in jRMD differed significantly from HC. Future prospective follow up will further elucidate the role of NVC in jRMD.

Juvenile systemic sclerosis (jSSc) is a rare but potentially life-threatening disease, with a prevalence of 3 to 4 in 1,000,000 children. Similar to that in adults,1interstitial lung disease (ILD) is the major cause of morbidity in children with systemic sclerosis (SSc) and occurs at similar prevalences.2

Objectives: Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. Methods: The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians’ and the patients’ global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Results: Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Conclusion: Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.

To analyze therapy adherence, safety, and outcome in adult patients with juvenile idiopathic arthritis (JIA) treated with the etanercept biosimilar BenepaliData from the prospective registry, JuMBO (Juvenile arthritis MTX/Biologics long-term Observation), were used for the analysis. JuMBO is a long-term observational cohort study. It follows adult patients with JIA who were formerly included in the national JIA biologic register (BiKeR Registry). Both registries provide individual trajectories of clinical data and outcomes from childhood to adulthood in JIA patients treated with disease-modifying anti-rheumatic drugs (DMARDs).Eighty-three patients from the German JuMBO registry were treated with BenepaliTolerability and effectiveness of the biosimilar Benepali

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

ObjectiveTo investigate the frequency in which the physician provides a global assessment of disease activity (PhGA) >0 and an active joint count (AJC)=0 in children with juvenile idiopathic arthritis (JIA) and search for determinants of divergence between the two measures.MethodsData were extracted from a multinational cross-sectional dataset of 9966 patients who had JIA by International League of Associations for Rheumatology criteria, were recruited between 2011 and 2016, and had both PhGA and AJC recorded by the caring paediatric rheumatologist at the study visit. Determinants of discordance between PhGA>0 and AJC=0 were searched for by multivariable logistic regression and dominance analyses.ResultsThe PhGA was scored >0 in 1647 (32.3%) of 5103 patients who had an AJC of 0. Independent associations with discordant assessment were identified for tender or restricted joint count >0, history of enthesitis, presence of active uveitis or systemic features, enthesitis-related or systemic arthritis, increased acute phase reactants, pain visual analogue scale (VAS)>0, and impaired physical or psychosocial well-being. In dominance analysis, tender joint count accounted for 35.43% of PhGA variance, followed by pain VAS>0 (17.72%), restricted joint count >0 (16.14%) and physical health score >0 (11.42%).ConclusionWe found that many paediatric rheumatologists did not mark a score of 0 for patients who they found not to have active joints. The presence of pain in joints not meeting the definition of active joint used in JIA was the main determinant of this phenomenon.

Summary Background Systemic sclerosis-associated interstitial lung disease (ILD) carries a high mortality risk; expert guidance is required to aid early recognition and treatment. We aimed to develop the first expert consensus and define an algorithm for the identification and management of the condition through application of well established methods. Methods Evidence-based consensus statements for systemic sclerosis-associated ILD management were established for six domains (ie, risk factors, screening, diagnosis and severity assessment, treatment initiation and options, disease progression, and treatment escalation) using a modified Delphi process based on a systematic literature analysis. A panel of 27 Europe-based pulmonologists, rheumatologists, and internists with expertise in systemic sclerosis-associated ILD participated in three rounds of online surveys, a face-to-face discussion, and a WebEx meeting, followed by two supplemental Delphi rounds, to establish consensus and define a management algorithm. Consensus was considered achieved if at least 80% of panellists indicated agreement or disagreement. Findings Between July 1, 2018, and Aug 27, 2019, consensus agreement was reached for 52 primary statements and six supplemental statements across six domains of management, and an algorithm was defined for clinical practice use. The agreed statements most important for clinical use included: all patients with systemic sclerosis should be screened for systemic sclerosis-associated ILD using high-resolution CT; high-resolution CT is the primary tool for diagnosing ILD in systemic sclerosis; pulmonary function tests support screening and diagnosis; systemic sclerosis-associated ILD severity should be measured with more than one indicator; it is appropriate to treat all severe cases; no pharmacological treatment is an option for some patients; follow-up assessments enable identification of disease progression; progression pace, alongside disease severity, drives decisions to escalate treatment. Interpretation Through a robust modified Delphi process developed by a diverse panel of experts, the first evidence-based consensus statements were established on guidance for the identification and medical management of systemic sclerosis-associated ILD. Funding An unrestricted grant from Boehringer Ingelheim International.

Objective Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. Methods Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. Results Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. Conclusion Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.

Juvenile localized scleroderma (jLS) is an orphan disease that can lead to cosmetic disfiguration and orthopedic problems. Two recent publications review the current recommendations regarding diagnosis, assessment, follow up and treatment of pediatric localized scleroderma cases, both of which suggest the Localized Scleroderma Cutaneous Assessment Tool as an important instrument to assess activity and damage. This review focuses on the systemic treatment of jLS. Systemic treatment includes synthetic and biologic disease-modifying antirheumatic drugs. Systemic therapy is indicated if the lesion crosses any joint, or leads to potential cosmetic disfiguration or orthopedic problems. The only controlled trial of systemic treatment has shown the efficacy of methotrexate, which is the first choice of treatment. It appears superior to phototherapy according to a recently published meta-analysis. In case of methotrexate intolerance, mycophenolate mofetil is an option. In case of methotrexate nonresponse, addition of mycophenolate mofetil, tocilizumab or abatacept seems to be effective. Future treatment options derived and extrapolated from adult trials regarding treatment of skin involvement of systemic scleroderma or fibrosis are promising, as the final pathway in the skin seems to be similar in both diseases.

The primary objective was twofold: (1) to determine whether the German version of a screening instrument for clinical practice for juvenile idiopathic arthritis (SICJIA) is reliable in identifying patients at risk for juvenile idiopathic arthritis (JIA), and (2) secondly whether a weighting scheme of individual questions improves its sensitivity. Data were collected and retrospectively analyzed based upon completed SICJIA questionnaires from patients and their guardians at their first clinical visit at the Hamburg Centre for Pediatric and Adolescence Rheumatology. All patients visited the center between August 2015 and July 2017. The survey included 12 disease-orientated questions. For evaluation, only questionnaires of patients diagnosed with JIA or with a non-inflammatory joint pain (NJP) were selected. Standard statistical techniques were used for evaluation. In total, 165 of 800 questionnaires could be used for evaluation. Of the 800 patients who completed questionnaires, 133 were diagnosed with JIA and 32 with NJP. The analysis of the individual questions was performed by comparing the rate of a positive response to the questions between the two groups. Four questions showed a significant difference by comparing the groups, using JIA patients with at least one active joint. The diagnostic accuracy of the weighted sum score increased from 64 to 68% to discriminate between the groups in comparison to the ordinary sum score. An optimal cutoff of 6.0 for referral to a pediatric rheumatologist was calculated. The validation of the SICJIA showed a discriminative difference in patients with clinical diagnosed JIA and a control group diagnosed with NJP. The weighted sum score performed better to differentiate between JIA and NJP patients. The modified SICJIA can be useful to identify patients at risk of JIA.

Background Uveitis in juvenile idiopathic arthritis (JIAU) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first line therapy, and disease modifying anti-rheumatic drugs (DMARDs) are commonly used. However, treatment has not been standardized. Methods Interdisciplinary guideline were developed with representatives from the German Ophthalmological Society, Society for Paediatric Rheumatology, Professional Association of Ophthalmologists, German Society for Rheumatology, parents’ group, moderated by the Association of the Scientific Medical Societies in Germany. A systematic literature analysis in MEDLINE was performed, evidence and recommendations were graded, an algorithm for anti-inflammatory treatment and final statements were discussed in a consensus meeting (Nominal Group Technique), a preliminary draft was fine-tuned and discussed thereafter by all participants (Delphi procedure). Results Consensus was reached on recommendations, including a standardized treatment strategy according to uveitis severity in the individual patient. Thus, methotrexate shall be introduced for uveitis not responding to low-dose (≤ 2 applications/day) topical corticosteroids, and a TNFalpha antibody (preferably adalimumab) used, if uveitis inactivity is not achieved. In very severe active uveitis with uveitis-related deterioration of vision, systemic corticosteroids should be considered for bridging until DMARDs take effect. If TNFalpha antibodies fail to take effect or lose effect, another biological should be selected (tocilizumab, abatacept or rituximab). De-escalation of DMARDs should be preceded by a period of ≥ 2 years of uveitis inactivity. Conclusions An interdisciplinary, evidence-based treatment guideline for JIAU is presented.

ZusammenfassungUngefähr 10% der Uveitiden beginnen im Kindesalter, mit einer Inzidenz von 6,9 auf 100 000 unter 14 Jahren und 26,6 auf 100 000 von 15 bis 24 Jahren. Sie werden unterteilt in infektiöse und nichtinfektiöse Uveitiden. Die Klassifikation der SUN-Gruppe erfolgt je nach Lokalisation des Auftretens und abhängend vom zeitlichen Verlauf. Die häufigste nicht-infektiöse Ursache bei Kindern ist die Juvenile idiopathische Arthritis, gefolgt von Morbus Behcet und Sarkoidose. Auch autoinflammatorischen Erkrankungen können mit einer Uveitis assoziiert sein. Die anteriore Uveitis tritt vorwiegend bei der Juvenilen idiopathischern Arthritis, der lokalisierten Sklerodermie und dem Kawasaki-Syndrom auf. Bei der intermediären Uveitis gibt es vor allem eine Assoziation mit Sarkoidose, Blau Syndrom, Tinu Syndrom und Multipler Sklerose. Eine posteriore Beteiligung ist für Morbus Behcet typisch, kann aber auch beim Cryopirin-assoziiertem Fiebersyndrom oder Cogan-Syndrom auftreten. Eine frühzeitige Diagnosestellung ist wichtig, um rechtzeitg eine effektive Therapie einleiten zu können und das Sehvermögen nicht zu gefährden.

Objective To study juvenile idiopathic arthritis (JIA) long-term outcomes in relation to the time of initiation of biologic disease-modifying antirheumatic drug (bDMARD). Methods Outcomes of JIA patients prospectively followed by the Biologika in der Kinderrheumatologie (BiKeR) and Juvenile Arthritis Methotrexate/Biologics Long-Term Observation (JuMBO) registers were analyzed with regard to drug-free remission and inactive disease, functional status and quality of life, and surgery. To analyze the influence of early bDMARD therapy on outcomes, patients were assigned to 3 groups based on the time from symptom onset to bDMARD start (G1: ≤2 years, G2: >2 to ≤5 years, and G3: >5 years). Propensity score-adjusted outcome differences were analyzed by multinomial logistic regression analyses among the groups. Results A total of 701 JIA patients were observed for mean ± SD 9.1 ± 3.7 years. At the last follow-up (disease duration mean ± SD 14.3 ± 6.1 years), 11.7% of patients were in drug-free remission, and 40.0% had inactive disease. More than half of the patients reported no functional limitation, while 5% had undergone arthroplasty, and 3% had eye surgery. At the 10-year time point, patients in G1 (n = 108) were significantly more likely to be in drug-free remission than those patients who began treatment later (G2, n = 199; G3, n = 259), with 18.5%, 10.1%, and 4.9%, respectively. Patients in G1 had significantly lower disease activity (clinical Juvenile Arthritis Disease Activity Score in 10 joints = 4.9), a better overall well-being (18.2% patient global assessment score = 0), and higher functional status (59.2% Health Assessment Questionnaire score = 0), compared to patients in G3 (7.1, 8.4%, and 43.7%, respectively). G1 patients required arthroplasty significantly less frequently than G3 patients and had significantly lower disease activity over time than patients in both G2 and G3. Conclusion Early DMARD treatment is associated with better disease control and outcomes, which supports the concept of a "window of opportunity" for JIA.

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

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

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 to March 2019, and baseline characteristics, effectiveness, and 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, and ACR-inactive disease definition. Safety assessments were based on adverse event (AE) reports. Results A total of 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 nine 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, and 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.

Objective Localized scleroderma is a skin fibrosing disorder that, if untreated, may result in severe disability. The purpose of this systematic review is to compare the present evidence concerning the effectiveness of Methotrexate versus phototherapy, alone or associated with Psoralen, in childhood localized scleroderma. Method A systematic search between January 1996 and May 2017 was performed to identify studies investigating the efficacy of Methotrexate (MTX) or phototherapy (UVA) for treating localized scleroderma with onset ≤18 years. Due to a lack of validated clinical criteria, four clinical response criteria were used to assess the treatment efficacy as primary outcome. We determined a combined estimate of the proportion of children responding to MTX and UVA. Results A total of 19 studies was included (8 MTX; 11 UVA). In the methotrexate group, 193 children were included in the analysis; in the phototherapy group, a total of 48 treated children. For both groups age, disease subtype, glucocorticoids (GCs) use, and side effects of treatment were also analyzed. The meta-analysis suggested that UVA and MTX protocols have both a favorable effect in active lesions of childhood localized scleroderma. However, MTX resulted significantly superior to UVA, with or without Psoralen. Conclusion Our study supports the combination of MTX and GCs in patients with a high risk of complication. Phototherapy with UVA1 could represent a therapeutic option in patients with limited scleroderma, where lesions do not cross joints and they do not lead to potential cosmetic changes.

Objective.To identify clinical features that define disease activity in pediatric localized scleroderma (LS), and determine their specificity and importance.Methods.We conducted a multicenter prospective study of patients with active and inactive LS skin lesions. A standardized evaluation of a single designated study lesion per subject was performed at 3 visits. We evaluated the pattern and correlation between assessed features and physician’s global assessments of activity (PGA-A).Results.Ninety of 103 subjects had evaluable data; 66 had active and 24 inactive disease. Subjects had similar age of onset, sex, and disease patterns. Linear scleroderma was the most common subtype. Features specific for active disease included erythema, violaceous color, tactile warmth, abnormal skin texture, and disease extension. Scores for these variables changed over time and correlated with PGA-A of the lesion. Active and inactive lesions could not be distinguished by the presence or level of skin thickening, either of lesion edge or center. However, in active lesions, skin thickening scores did correlate with PGA–A scores. Regression analysis identified the combination of erythema, disease extension, violaceous color, skin thickening, and abnormal texture as predictive of PGA-A at study entry. Damage features were common irrespective of activity status.Conclusion.We identified variables strongly associated with disease activity, expanding upon those used in current measures, and determined their relative importance in physician activity scoring. Skin thickening was found to lack specificity for disease activity. These results will help guide development of a sensitive, responsive activity tool to improve care of patients with LS.

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Juvenile localized scleroderma (jLS), also known as morphea, is an orphan disease. Pediatric guidelines regarding diagnosis, assessment, and management are lacking.Our objective was to develop minimum standards of care for diagnosis, assessment, and management of jLS. A systematic review was undertaken to establish the pediatric evidence for assessment and monitoring of jLS. An expert panel, including members of the Pediatric Rheumatology European Society (PRES) Scleroderma Working Group, were invited to a consensus meeting where recommendations were developed based on evidence graded by the systematic review and, where evidence was lacking, consensus opinion. A nominal technique was used where 75% consensus was taken as agreement. Recommendations for diagnosis, assessment, and management were developed. Due to a lack of pediatric evidence, these were primarily consensus driven. Careful assessment for extra-cutaneous manifestations including synovitis, brain involvement, and uveitis were key features together with joint assessments between Dermatology and Rheumatology to improve and standardize care.Management of jLS is varied. These recommendations should help provide standardization of assessment and care for those with this rare and potentially debilitating condition. What is Known: • Children with juvenile localized scleroderma (jLS) are managed by a number of specialties including pediatric rheumatologists and dermatologists, sometimes in shared clinics. Studies have shown that management varies considerably and that there are notable differences between specialties [1]. • There is very little published guidance on management of jLS. What is new: • These recommendations aim to standardize diagnosis, assessment, and management through review of pediatric evidence and consensus agreement. • Joint review of patients by both pediatric rheumatologists and dermatologists is recommended.

Background:The calcium-binding proteins S100A8/A9 (calprotectin) and S100A12 (extracellular newly identified receptor for advanced glycation end-products binding protein [EN-RAGE]) are involved in multiple signalling pathways to mediate inflammation, can be secreted by activated monocytes/macrophages and exhibit cytokine-like extracellular functions. Circulating levels of these proteins have been associated with disease and clinical responses in systemic juvenile idiopathic arthritis (sJIA), including treatment response.1 Studies suggest that serum S100A8/A9 and S100A12, which are released at inflammation sites, are more specific biomarkers of local inflammation (e.g. in the synovium) than systemic biomarkers such as CRP and ESR.2,3Objectives:To investigate if baseline S100A8/A9 and S100A12 predict clinical response to abatacept treatment in polyarticular JIA (pJIA), and to assess whether changes from baseline in S100A8/A9 or S100A12 can be better prognostic markers for response to abatacept treatment than CRP in pJIA.Methods:Data are from a phase III trial of SC abatacept for the treatment of pJIA (NCT01844518).4 This 24-month, single-arm, open-label, international, multicentre, two-part study included male and female patients with pJIA aged 2–17 years. This analysis examined the correlation between biomarkers (S100A8/A9, S100A12 and high-sensitivity CRP [hsCRP]) and disease activity (measured using Juvenile Arthritis Disease Activity Score [JADAS]) at baseline, baseline biomarker values as predictors of future treatment response (ACR and JADAS endpoints), and the correlation between change from baseline in biomarker values and treatment response at Day 113.Results:Of 219 total patients, 158 (72%) had S100A8/A9 values and 155 (71%) had S100A12 values at baseline. Median S100A8/A9 and S100A12 values were 3295 ng/mL (normal range, 716–3004 ng/mL) and 176 ng/mL (normal range, 32–385 ng/mL), respectively. S100A8/A9, S100A12 and hsCRP (median 0.20 mg/dL; normal ≤0.6 mg/dL) had a low-to-moderate but significant association with disease activity at baseline; coefficients for associations between JADAS71-CRP low disease activity (LDA) and the biomarkers S100A8/A9, S100A12 and hsCRP were 0.23 (p=0.0038), 0.16 (p=0.0448) and 0.26 (p=0.0001), respectively. Baseline S100A8/A9 level above the median was associated with lower odds of ACR100 at Day 113 (p=0.0052). Figure 1 shows the associations of baseline biomarker values with Day 113 ACR and JADAS scores in the overall population. Baseline S100A8/A9 or S100A12 did not significantly influence ACR50 or ACR70 responses at Day 113, but high baseline values were associated with reduced odds of ACR90 (p=0.01), ACR100 (p=0.005), ACR-inactive disease (ID) (p=0.0001), and JADAS71-CRP (LDA) (p=0.02). By Day 477, elevated baseline S100A12 was still significantly associated with lower odds of ACR100 overall (0.467; p=0.0248) but baseline S100A8/A9 was not; at Day 645, neither was significantly associated with ACR100 response. At Day 113, changes from baseline in S100A8/A9 and S100A12 were correlated with ACR100 (coefficients of 0.22 [p=0.0082] and 0.26 [p=0.0015], respectively) and with ACR-ID (0.22 [p=0.0067] and 0.26 [p=0.0014], respectively); change in hsCRP was not significantly correlated with disease response.Conclusion:S100A8/A9 and S100A12 may serve as prognostic biomarkers to predict response to abatacept treatment at Day 113. Changes from baseline S100A8/A9 and S100A12 levels were more highly correlated with efficacy outcomes including ACR100 and ACR-ID at Day 113 compared with hsCRP.References:[1]Aljaberi N, et al. Pediatr Rheumatol Online J 2020;18:7.[2]Hammer H, et al. Arthritis Res Ther 2011;13:R178.[3]Nordal HH, et al. BMC Musculoskelet Disord 2014;15:335.[4]Brunner H, et al. Arthritis Rheumatol 2018;70:1144–1154.Acknowledgements:Professional medical writing and editorial assistance was provided by Rob Coover, MPH, at Caudex and was funded by Bristol Myers Squibb.Disclosure of Interests:Nicolino Ruperto Speakers bureau: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Consultant of: NR has received honoraria for consultancies or speaker bureaus (< 10.000 USD each) from the following pharmaceutical companies in the past 3 years: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: The IRCCS Istituto Giannina Gaslini (IGG), where NR works as full-time public employee has received contributions (>10.000 USD each) from the following industries in the last 3 years: Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi. This funding has been reinvested for the research activities of the hospital in a fully independent manner, without any commitment with third parties., Grant Schulert Speakers bureau: Novartis, Consultant of: SOBI, Alyssa Sproles: None declared, Sherry Thornton: None declared, Gabriel Vega Cornejo Speakers bureau: AbbVie, Grant/research support from: Bristol Myers Squibb, Eli Lilly, Janssen, Parexel, Sanofi, Jordi Anton Speakers bureau: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Consultant of: AbbVie, Gebro, GlaxoSmithKline, Novartis, Pfizer, Roche, Sobi, Grant/research support from: AbbVie, Amgen, Gebro, GlaxoSmithKline, Lilly, Novartis, Novimmune, Pfizer, Roche, Sanofi, Sobi, Ruben Cuttica Speakers bureau: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Paid instructor for: AbbVie, Novartis, Pfizer, Roche, Consultant of: AbbVie, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Novartis, Pfizer, Roche, UCB, Michael Henrickson: None declared, Ivan Foeldvari Consultant of: Bristol Myers Squibb, Gilead, Hexal, MEDAC, Novartis, Pfizer, Sanofi, Daniel Kingsbury Consultant of: Pfizer, Margarita Askelson Consultant of: Currently working for Syneos Health providing services to Bristol Myers Squibb, Jinqi Liu Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sumanta Mukherjee Shareholder of: Bristol Myers Squibb, GlaxoSmithKline, Employee of: Bristol Myers Squibb, GlaxoSmithKline, Robert Wong Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Daniel J Lovell Speakers bureau: Genentech, Wyeth Pharm, Consultant of: Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Hoffman-La Roche, Novartis, Pfizer, Regeneron, Takeda, UBC, Wyeth Pharma, Xoma, Alberto Martini Speakers bureau: AbbVie, Novartis, Consultant of: AbbVie, Eli Lilly, EMD Serono, Idorsia, Janssen, Novartis, Pfizer, Alexei Grom Consultant of: AB2Bio, Novartis, Sobi (NovImmune), Grant/research support from: AB2Bio, Novartis, Sobi (NovImmune), Hermine Brunner Speakers bureau: GlaxoSmithKline, Novartis, Pfizer, Roche, Paid instructor for: Novartis, Pfizer (funds go to CCHMC/employer), Consultant of: Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, UCB (funds go to CCHMC/employer), Grant/research support from: Bristol Myers Squibb, Pfizer (funds go to CCHMC/employer).

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

Background Evidence is lacking for safe and effective treatments for juvenile localised scleroderma (JLS). Methotrexate (MTX) is commonly used first line and mycophenolate mofetil (MMF) second line, despite a limited evidence base. A head to head trial of these two medications would provide data on relative efficacy and tolerability. However, a frequentist approach is difficult to deliver in JLS, because of the numbers needed to sufficiently power a trial. A Bayesian approach could be considered. Methods An international consensus meeting was convened including an elicitation exercise where opinion was sought on the relative efficacy and tolerability of MTX compared to MMF to produce prior distributions for a future Bayesian trial. Secondary aims were to achieve consensus agreement on critical aspects of a future trial. Results An international group of 12 clinical experts participated. Opinion suggested superior efficacy and tolerability of MMF compared to MTX; where most likely value of efficacy of MMF was 0.70 (95% confidence interval (CI) 0.34-0.90) and of MTX was 0.68 (95% CI 0.41-0.8). The most likely value of tolerability of MMF was 0.77 (95% CI 0.3-0.94) and of MTX was 0.62 (95% CI 0.32-0.84). The wider CI for MMF highlights that experts were less sure about relative efficacy and tolerability of MMF compared to MTX. Despite using a Bayesian approach, power calculations still produced a total sample size of 240 participants, reflecting the uncertainty amongst experts about the performance of MMF. Conclusions Key factors have been defined regarding the design of a future Bayesian approach clinical trial including elicitation of prior opinion of the efficacy and tolerability of MTX and MMF in JLS. Combining further efficacy data on MTX and MMF with prior opinion could potentially reduce the pre-trial uncertainty so that, when combined with smaller trial sample sizes a compelling evidence base is available.

Juvenile systemic sclerosis (jSSc) is a rare, severe autoimmune disease associated with life-threatening multiorgan inflammatory-driven fibrosis. Recognition early in the disease process, when treatment is more effective, is critical. We outline insights from the authors, who specialize and host jSSc cohorts, combined with recent literature review combining available juvenile-onset and applicable adult-onset studies regarding SSc evaluation, which can be extrapolated to children. Practice tips are provided for each main organ system.

Introduction Juvenile localized scleroderma (jlSc) usually responds well to treatment with methotrexate or mycophenolate. In case of nonresponse or partial response, tocilizumab (TOC) appears to be a promising option. Methods Participants of the Pediatric Rheumatology Email Board were asked to report patients with jlSc treated with TOC. Results Six centers responded and reported 11 patients. The mean age at disease onset was 5.5 years. Disease duration at time of the initiation of TOC was 4.5 years. A total of 5 patients had linear subtype, 2 Parry Romberg syndrome, and 1 morphea en coup de sabre. Three had a generalized subtype, 2 a mixed subtype, and 1 a limited subtype/morphea. Before starting TOC, 10 of 11 patients received methotrexate, 7/11 combination methotrexate and mycophenolate, 1 abatacept, and 1 antitumor necrosis factor therapy. The indications for starting TOC were: (i) an increase in the score of the Localized Scleroderma Activity Index (mLoSSI) in 9 patients; and (ii) evidence of increased extra-cutaneous activity in 2 patients. The mean duration of TOC therapy was 14.75 months. Three of 11 patients received TOC as monotherapy, and 8/11 as combination therapy. Therapy success was reflected by a decreased mLoSSI in 9/11 patients, no new lesion occurrence, and – with Parry Romberg syndrome subtype – no increase in facial atrophy. In 8/8 patients, both the physicians’ and patients’ global assessment of disease activity decreased. In 3/3 patients, the number of active joints decreased. The mean modified Rodnan skin score decreased from 8.7 to 5.6. Conclusions In this small cohort of patients, TOC seems to be a promising rescue medication.

Background:Maintenance of clinical response over time has been shown in individual patients (pts) with polyarticular-course juvenile idiopathic arthritis (pJIA) treated with SC abatacept (ABA).1It is unknown whether each individual pt with sustained efficacy also consistently maintains the previously reported shorter-term benefits on patient-reported outcomes (PROs)2,3over time.Objectives:Investigate whether combined efficacy and stringent, optimal PRO responses to ABA treatment are maintained by individual pts with pJIA over time.Methods:In this analysis of the intent-to-treat population, pts in two age cohorts (2–5 and 6–17 yrs) who achieved clinical response to weekly SC ABA (10–4) were followed for 2 yrs. Stringent efficacy outcomes (Juvenile Arthritis Disease Activity Score 27 [JADAS27] minimal disease activity [MDA; ≤3.8] and inactive disease [ID; ≤1] status) were combined with optimal PRO endpoints (childhood [C]HAQ-DI=0, Parental Global Assessment [PaGA] ≤1 and Pain visual analogue scale [VAS] Results:219 pts entered the study (46 [21.0%] 2–5 yrs; 173 [79.0%] 6–17 yrs); a subgroup of these pts achieved a clinical response at Mo 4 (Table 1). Many pts who achieved JADAS27 MDA or JADAS27 ID combined with optimal PROs at Mo 4 sustained their response at Mo 13, and at both Mo 13 and Mo 21 in the 2–5-yr and 6–17-yr cohorts (Table 1). Across the cohorts, 33–88% of pts maintained a combined JADAS27 MDA with optimal PRO responses through Mo 21. Where estimable, median times to combined efficacy and specific optimal PRO responses were consistent across the cohorts (Table 2; Figs 1, 2).Table 1.Proportion of pts with combined efficacy and optimal PRO responses at Mos 4, 13 and 21EndpointResponders at Mo 4Responders at Mos 4 and 13*Responders at Mos 4, 13 and 21*2–5 yrs (n=46)6–17 yrs (n=173)2–5 yrs6–17 yrs2–5 yrs6–17 yrsJADAS27 MDA and CHAQ-DI=09 (20)34 (20)5/9 (56)25/34 (74)3/9 (33)16/34 (47)JADAS27 MDA and PaGA ≤18 (17)14 (8)8/8 (100)7/14 (50)7/8 (88)5/14 (36)JADAS27 MDA and Pain VAS 28 (61)70 (41)25/28 (89)58/70 (83)21/28 (75)43/70 (61)JADAS27 ID and CHAQ-DI=07 (15)20 (12)2/7 (29)13/20 (65)1/7 (14)9/20 (45)JADAS27 ID and PaGA ≤16 (13)10 (6)4/6 (67)4/10 (40)4/6 (67)4/10 (40)JADAS27 ID and Pain VAS 17 (37)31 (18)10/17 (59)22/31 (71)8/17 (47)17/31 (55)Data are n (%) or n/N (%). *% based on n of pts who achieved response at Mo 4 (denominator)Table 2.Kaplan–Meier estimates for median (95% CI) times (mos) to achieving combined efficacy and optimal PRO responsesEndpoint2–5 yrs6–17 yrsJADAS27 MDA and CHAQ-DI=021.5 (6.8, NE)21.5 (13.1, 24.4)JADAS27 MDA and PaGA ≤1NE (15.9, NE)24.6 (24.3, NE)JADAS27 MDA and Pain VAS 2.8 (1.9, 2.9)3.8 (3.7, 6.6)JADAS27 ID and CHAQ-DI=0NE (18.4, NE)24.4 (18.7, NE)JADAS27 ID and PaGA ≤1NE (21.3, NE)24.6 (24.3, NE)JADAS27 ID and Pain VAS 3.8 (3.8, 10.3)13.2 (10.3, 15.9)NE=not estimableConclusion:Many individuals with pJIA who achieved stringent efficacy and PRO measures with weekly SC abatacept by Mo 4 sustained them over 2 years. Time to achieve combined efficacy and Pain VAS References:[1]Ruperto N, et al.Ann Rheum Dis2019;78:99–100 (abstr OP0056)[2]Brunner H, et al.Arthritis Rheumatol2019;71(suppl 10):abstr 2707[3]Ruperto N, et al.Ann Rheum Dis2017;76:75 (abstr OP0058)[4]Brunner HI, et al.Arthritis Rheumatol2018;70:1144–54Acknowledgments:Katerina Kumpan, PhD, Caudex; funding: Bristol-Myers SquibbDisclosure of Interests: :Hermine Brunner Consultant of: Hoffman-La Roche, Novartis, Pfizer, Sanofi Aventis, Merck Serono, AbbVie, Amgen, Alter, AstraZeneca, Baxalta Biosimilars, Biogen Idec, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Janssen, MedImmune, Novartis, Pfizer, and UCB Biosciences, Speakers bureau: GSK, Roche, and Novartis, Nikolay Tzaribachev: None declared, Ingrid Louw Consultant of: Amgen, Novartis, Pfizer, Roche (advisory boards), Inmaculada Calvo Grant/research support from: Bristol-Myers Squibb, Clementia, GlaxoSmithKline, Hoffman-La Roche, Merck Sharpe & Dohme, Novartis, Pfizer, Sanofi, Speakers bureau: AbbVie, GlaxoSmithKline, Hoffman-La Roche, Novartis, Francisco Zapata: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Chugai, Eli Lilly, Novartis, Pfizer, Daniel Kingsbury: None declared, Maria Gastanaga Grant/research support from: Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Roche, Carine Wouters Grant/research support from: GlaxoSmithKline, Pfizer, Roche, Johannes Breedt: None declared, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Marleen Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Margarita Askelson Consultant of: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Alberto Martini Consultant of: AbbVie, Eli Lily, EMD Serono, Janssen, Novartis, Pfizer, UCB, Daniel J Lovell Consultant of: Abbott (consulting and PI), AbbVie (PI), Amgen (consultant and DSMC Chairperson), AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb (PI), Celgene, Forest Research (DSMB Chairman), GlaxoSmithKline, Hoffman-La Roche, Janssen (co-PI), Novartis (consultant and PI), Pfizer (consultant and PI), Roche (PI), Takeda, UBC (consultant and PI), Wyeth, Employee of: Cincinnati Children’s Hospital Medical Center, Speakers bureau: Wyeth, Nicolino Ruperto Grant/research support from: Bristol-Myers Squibb, Eli Lily, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sobi (paid to institution), Consultant of: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda, Speakers bureau: Ablynx, AbbVie, AstraZeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lily, EMD Serono, GlaxoSmithKline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sanofi, Servier, Sinergie, Sobi, Takeda

Background:Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 per 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is the largest multinational registry that prospectively collects information about jSSc patients.Objectives:Evaluation of the jSSc patients at the time of inclusion in the JSSIC.Methods:Patients were included in the JSSIC if they fulfilled the adult ACR/EULAR classification criteria for systemic scleroderma, if they presented the first non-Raynaud symptom before 16 years of age and if they were younger than 18 years of age at time of inclusion. Patients’ characteristics at time of inclusion were evaluated.Results:Until 15thof December 2019 hundred fifty patients were included, 83% of them being Caucasian and 80% female. The majority had the diffuse subtype (72%) and 17% of all jSSc had overlap features. The mean age of first presentation of Raynaud´s phenomenon was 9.8 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc) (p=.197). The mean age at first non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.2 years in the ljSSc (p=0.247). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group.Significant differences were found between the groups regarding mean modified Rodnan skin score, 18.2 in the djSSc vs 6.2 in the ljSSc (p=0.02); presence of Gottron´s papulae (djSSc 30% vs ljSSc 13%, p=0.43);presence of teleangiectasia (djSSc 42% vs 18% ljSS, p=0.01); history of ulceration (djSSc 42% vs 18% ljSSc,p=0.008); 6 Minute walk test below the 10thpercentile (djSSc 85% vs ljSSc 54%, p=0.044), total pulmonary involvement (djSSc 49% vs ljSSc 31%, p=0.045), cardiac involvement (ljSSc 17% vs djSSc 3%, p=0.002). djSSc patients had significantly worse scores for Physician Global Assessment of disease activity compared to ljSSc patients (VAS 0-100) (40 vs 15) (p=0.001) and for Physician Global Assessment of disease damage (VAS 0-100) (36 vs 17) (p=0.001).There were no statistically significant differences in the other presentations. Pulmonary hypertension occurred in approximately 6% in both groups. No systemic hypertension or renal crisis was reported. ANA positivity was 90% in both groups. Anti-Scl70 was positive in 35% in djSSc and 36% in the ljSSc group. Anticentromere positivity occurred in 3% in the djSSc and 7% in the ljSSc group.Conclusion:In this unique large cohort of jSSc patients there were significant differences between djSSc and ljSSc patients at time of inclusion into the cohort regarding skin, vascular, pulmonary and cardiac involvement. According to the physician global scores the djSSc patients had a significantly more severe disease. Interestingly the antibody profile was similar in both scleroderma phenotypes.Supported by the “Joachim Herz Stiftung”Disclosure of Interests: :Ivan Foeldvari Consultant of: Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Brian Feldman Consultant of: DSMB for Pfizer, OPTUM and AB2-Bio, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, edoardo marrani: None declared, Mikhail Kostik: None declared, Natalia Vasquez-Canizares: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Anjali Patwardhan: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Sujata Sawhney: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Daniela Kaiser: None declared, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in …

BackgroundJuvenile idiopathic arthritis is one of the most prevalent chronic inflammatory diseases in children. Evidence suggests that early effective treatment minimises the burden of disease during childhood and in further life. We hypothesise that a guided treat-to-target (T2T) approach is superior to routine care in polyarticular juvenile idiopathic arthritis (pJIA) in terms of reaching a clinical remission after 12 months of treatment.MethodsPatients with early and active pJIA were enrolled. Targets for treatment were the following: Recognisable Juvenile Arthritis Disease Activity Score (JADAS) improvement after 3 months, acceptable disease at 6 months, minimal disease activity at 9 months and as primary endpoint remission after 12 months. Initially, patients received methotrexate. Failure to meet a defined target required treatment modification at the specified intervals. The choice of biologics was not influenced by the protocol. Finally, T2T patients were compared with a cohort of matched controls of patients with pJIA with unguided therapy documented by BIKER.ResultsSixty-three patients were enrolled. Treatment targets after 3/6/9 and 12 months were reached by 73%/75%/77% and 48% of patients. Fifty-four patients completed the protocol. Compared with matched controls, on T2T guidance significantly more patients reached JADAS remission (48% vs 32%; OR 1.96 (1.1–3.7); p=0.033) and JADAS minimal disease activity (JADAS-MDA) (76% vs 59%; OR 2.2 (1.1–4.4); p=0.028). Patients from the T2T cohort received a biologic significantly more frequent (50% vs 9% after 12 months; OR 9.8 (4.6–20.8); pConclusionThe T2T concept was feasible and superior to unguided treatment. High rates of patients reached JADAS-MDA and JADA remission after 12 months. Approximately half of the patients achieved their therapy goals without a biologic.

Background Juvenile Idiopathic Arthritis associated Uveitis (JIA-U) represents its most frequent extra-articular manifestation and the main cause of childhood uveitis in in developed countries. The broad variety of outcome measures utilized makes the comparison of the disease course, risk for complications, impairment in visual function, and responses to treatment quite difficult. Our aim was to summarize evidence regarding the current availability of outcome measures in JIA-U. Methods A systematic review between January 2000 and December 2018 was performed to identify studies investigating outcome measures used in JIA-U. Results The initial search identified 8254 articles of which 89 were potentially eligible. After the full text revision, a total of 27 studies, including 2 RCTs, were included. Among these studies 12 outcome measures for JIA-U use have been identified (grade of cells in the AC, grade of flare in the AC, VA, amblyopia, structural complications, use and sparing of oral corticosteroids and immunosuppressive drugs, surgery requirement, biomarkers, bilateral disease, JIA persistence, quality of life assessments, uveitis subtype). As regards primary outcome measures, 44% among studies included one or more variables related to disease activity (i.e. grade of flare, grade of cells); 56% included visual function performance (i.e. visual acuity); 68% (17/25) included one or more variables of disease-associated tissue damage or complications (i.e. cataract, amblyopia); 24% included disease features (i.e. bilateral disease; uveitis subtype); 44% included laboratory features (i.e. biomarkers); 8% included JIA features (i.e. persistence of disease); 12% included quality of life (i.e. EYE-Q); 44% included management (i.e. use and sparing of oral corticosteroids and other immunosuppressive drugs; surgery requirement). Conclusions Our systematic review surveys the heterogeneity around outcome measures related to JIA-U in children, even in RCTs. It does not provide the solution to overcome the heterogeneity in uveitis studies, but it does provide an estimate of the scale of the problems and provides data to inform this important debate; highlighting the requirement to obtain a new consensus regarding a common approach to identify suitable and efficient outcome measures in JIA-U.

Background Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is a multinational registry that prospectively collects information regarding patients with this disease in a standardized manner. Objectives Evaluation of the jSSc patients at the time of inclusion in the JSSIC. Methods Patients were included in the JSSIC if they fulfilled the adult classification criteria, if they presented the first non Raynaud symptom before 16 years old and if they were younger than 18 years of age at the time of inclusion. Patients’ characteristics at time of inclusion were evaluated. Results Currently, the cohort includes 120 patients, being 89% Caucasian and 80% female. The majority had diffuse subtype (74%) and 18% had overlap features. The mean age of onset of Raynaud phenomenon was 9.7 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc). The mean age of non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.4 years in the ljSSc (p=0.041). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group. Mean Modified Rodnan skin score was 17.5 in the djSSc and 7.3 in the ljSSc (p=0.002). Gottron papulae were significantly more common in the djSSc compared to ljSSc group (29% vs 6%, respectively) (p=0.011). History of ulceration was significantly more common in the djSSc than in the ljSSc group (57% vs 30%, respectively) (p=0.004). FVC Conclusion In this large cohort of jSSc patients there were surprisingly not many significant differences between djSSc and ljSSc. According to the physician global scores the djSSc patients have a significantly more severe disease. Disclosure of Interests Ivan Foeldvari Consultant for: Chugai, Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Valda Stanevicha: None declared, Flavio R. Sztajnbok: None declared, Maria T. Tererri: None declared, Ekaterina Alexeeva: None declared, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Maria Katsikas: None declared, Vanessa Smith: None declared, Tadej Avcin: None declared, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Thomas Lehman: None declared, Walter Alberto Sifuentes-Giraldo: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Maria Jose Santos: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson: None declared, Blanca Bica: None declared, Juergen Brunner: None declared, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Dragana Lazarevic: None declared, Kirsten Minden Consultant for: AbbVie, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared

Background Timely access to specialized and multidisciplinary care is a core principle in the management of JIA patients and crucial to achieve the best possible outcome for children and adolescents with JIA. Objectives To assess satisfaction with access to specialized care and used health care services of families with children with JIA and to identify factors associated with unmet needs. Methods Parents of JIA patients enrolled in the early JIA cohort study ICON completed the Child Healthcare Questionnaire on Satisfaction, Utilisation and Needs (CHC-SUN)1 and the Family Burden Questionnaire (FaBel) 3 months after enrolment. The socioeconomic status, disease activity, patients’ functional ability and quality of life were also assessed. Factors associated with unmet needs were identified by logistic regression analysis. Results Data were available from 835 families with children diagnosed with JIA 3 months (median, IQR 1-6) after symptom onset and cared for by paediatric rheumatologists (68% females). At assessment (4.6 months after diagnosis, median), 67% of patients received non-steroidal anti-inflammatory drugs, 50% received conventional synthetic DMARDs and 8% biologic DMARDs. In addition, the following health care services were utilized: 84% physiotherapy, 23% occupational therapy, 21% supply with physical aids, 17% telephone counselling, 15% health education, 13% social worker services, and 11% psychological counselling. Unmet needs were most frequently reported for health education (19%), rehabilitation services (11%), psychological counselling (11%), self-help groups (10%), and lowest for physiotherapy (2%). Unmet needs varied depending on the type of service and JIA category (Table). They were more frequently observed in families with higher burden as indicated by FaBel, but were not associated with migration background and socioeconomic status. Most parents were generally satisfied with their child’s health care (satisfied 30%, very satisfied 42%, extremely satisfied 23%). Satisfaction was highest with the behaviour of doctors and lowest with school-related services (e.g. 36% not or partly satisfied with teachers’ knowledge about the child’s illness) and diagnosis/information (e.g. 29% not or partly satisfied with the time required for the diagnosis). Conclusion There are, although infrequently, unmet needs and dissatisfaction with health services among families with children who have JIA and receive specialized care. Whether these deficits are relevant for long-term JIA outcomes will be further investigated in the ICON study. Reference [1] Schmidt S, Thyen U, Chaplin J, Mueller-Godeffroy E; European DISABKIDS Group. Cross-cultural development of a child health care questionnaire on satisfaction, utilization, and needs. Ambul Pediatr. 2007;7:374-82. Acknowledgement Funding by Federal Ministry of Research: 01 ER 1504A Disclosure of Interests Michaela Heinrich: None declared, Jens Klotsche: None declared, Claudia Sengler: None declared, Martina Niewerth: None declared, Frank Weller-Heinemann: None declared, Peter Haas Grant/research support from: Pfizer, Gerd Horneff: None declared, Toni Hospach Speakers bureau: Chugai, Roche, Novartis, Kirsten Moenkemoeller: None declared, Angelika Thon: None declared, Ivan Foeldvari Consultant for: Chugai, Novartis, Kirsten Minden Consultant for: AbbVie

Background Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in a 1 000 000 children(1). Currently there is nearly no data published about the course of jSSc patients with standardized assessment. We report our date from Juvenile Scleroderma Inception cohort (JSSIC) with a follow up of 24 months. Objectives: to evaluate the organ involvement and patient reported outcomes (PRO) during the first 24 months in the JSIC Methods The JSSIC is a prospective multicenter registry of patients with jSSc, who fulfill the adult classification criteria(2), and presented the first non-Raynaud symptom before 16 years of age and were younger then 18 years at the time of inclusion in the JSSIC. Patients who were followed at least 24 months in the JSSIC, were evaluated. Results 52 patients were followed at least 24 months in the registry. 77% were female and 77% had diffuse subtype. 19% had overlap features. Mean disease duration at time of inclusion was 3.2 years. Mean age of at Raynaud’s onset was 8.8 years and the first non-Raynaud’s symptom 9.4 years. 85% received DMARDs at the time of inclusion and 96% after 24 months. 88% of the patients were ANA positive, 35% anti-Scl70 positive and 3% anticentromere positive. The mean modified skin score decreased from 14.3 to 12.6. The frequency of Raynaud’s stayed around 87%. The frequency of the nailfold capillary changes increased from 56% to 63%, but the frequency of active ulcerations stayed stable around 21%. The number of patients with FVC Several PROs improved significantly. Patient global disease activity (VAS 0-100) changed from 46 to 29 (p=0.002), patient global disease damage (VAS 0-100) from 46 to 28 (p=0.02) and patient Raynaud activity VAS 0-100) from 27 to 14 (p=0.009) as physician global disease activity (VAS 0-100) from 43 to 29 (p=0.021) and physician global disease damage from 46 to 28 (P=0.01). Conclusion Over the 24 months observation period patient and physician related outcomes improved significantly. Regarding organ involvement there was an increase in patients of pulmonary hypertension and joint contractures. References [1] Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90. [2] van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013;65(11):2737-47. Disclosure of Interests Ivan Foeldvari Consultant for: Chugai, Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Maria T. Tererri: None declared, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Tadej Avcin: None declared, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Maria Katsikas: None declared, Dana Nemcova: None declared, Maria Jose Santos: None declared, Cristina Battagliotti: None declared, Lillemor Berntson: None declared, Juergen Brunner: None declared, Liora Harel: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Kirsten Minden Consultant for: AbbVie, Monika Moll: None declared, Anjali Patwardhan: None declared, Kathryn Torok: None declared, Nicola Helmus: None declared

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 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] Gronlund 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. Ubergewicht 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 Horstermann: 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