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Objectives Burden of comorbidities are largely unknown in JIA. From 2000, national and international patient registries were established to monitor biologic treatment, disease activity and adverse events in patients with JIA. The aim of this analysis was to investigate in parallel, for the first time, three of the largest JIA registries in Europe/internationally—UK JIA Biologic Registers (BCRD/BSPAR-ETN), German biologic registers (BiKeR/JuMBO), multinational Pharmachild—to quantify the occurrence of selected comorbidities in patients with JIA. Methods Information on which data the registers collect were compared. Patient characteristics and levels of comorbidity were presented, focussing on four key conditions: uveitis, MAS, varicella, and history of tuberculosis. Incidence rates of these on MTX/biologic therapy were determined. Results 8066 patients were registered into the three JIA registers with similar history of the four comorbidities across the studies; however, varicella vaccination coverage was higher in Germany (56%) vs UK/Pharmachild (16%/13%). At final follow-up, prevalence of varicella infection was lower in Germany (15%) vs UK/Pharmachild (37%/50%). Prevalence of TB (0.1–1.8%) and uveitis (15–19%) was similar across all registers. The proportion of systemic-JIA patients who ever had MAS was lower in Germany (6%) vs UK (15%) and Pharmachild (17%). Conclusion This analysis is the first and largest to investigate the occurrence of four important comorbidities in three JIA registries in Europe and the role of anti-rheumatic drugs. Combined, these three registries represent one of the biggest collection of cases of JIA worldwide and offer a unique setting for future JIA outcome studies.

OBJECTIVE: To evaluate the long-term efficacy and safety of canakinumab and explore prediction of response in patients with systemic juvenile idiopathic arthritis (JIA) with or without fever at treatment initiation. METHODS: At enrollment, patients with active systemic JIA (ages 2 to

To assess the possible impact conferred by co-existing variants in MEditerranean FeVer (MEFV) and other genes on systemic autoinflammatory disease (SAID) phenotype.Consecutive patients (n = 42) who underwent screening for SAIDs by next generation sequencing (NGS) targeting 26 genes, and carried at least one MEFV gene variant, were retrospectively studied. A total of 63 MEFV gene variants mainly located in exon 10 (n = 29) and exon 2 (n = 19) were identified in 21 patients with juvenile- and 21 with adult-onset disease.The candidate clinical diagnosis was Familial Mediterranean Fever (FMF) in 11, polygenic SAIDs (PFAPA, Still's disease, atypical SAPHO and inflammatory bowel disease) in 9, whereas the disease could not be clinically defined in 22 patients. Notably, 33 out of the 42 patients (79%) had at least one co-existing variants in 19 genes other than MEFV. NGS confirmed all clinical diagnoses and helped defining diagnosis in 59% of the remaining cases. Patients with undefined SAIDs (n = 9) or atypical FMF phenotype (n = 12) carried significantly more disease-causing variants in genes other than MEFV compared to patients with typical FMF (n = 9). More than one variants in these genes were significantly associated with adult-onset disease, while disease-causing variants in the same genes were also associated with an overall more severe SAID phenotype.Co-existing variants in SAID-related genes may explain the phenotypic variability of these diseases. Further studies should validate combined molecular and clinical data in order to better understand the cumulative gene dosage effect and improve the classification of these patients.

Objective To describe the clinical characteristics, treatment, and outcomes of a multinational cohort of patients with macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). Study design International pediatric rheumatologists were asked to collect retrospectively the data of patients with the co-occurrence of MAS and TMA. Clinical and laboratory features of patients with systemic juvenile idiopathic arthritis (sJIA)-associated MAS and TMA were compared with those of an historical cohort of patients with sJIA and MAS. Results Twenty-three patients with MAS and TMA were enrolled: 17 had sJIA, 2 systemic lupus erythematosus, 1 juvenile dermatomyositis, 1 mixed connective tissue disease, and 2 undifferentiated connective tissue disease. Compared with the historical cohort of MAS, patients with sJIA with coexistent MAS and TMA had higher frequencies of renal failure and neurologic involvement, hemorrhage, jaundice, and respiratory symptoms, as well as more severe anemia and thrombocytopenia, higher levels of alanine aminotransferase, lactate dehydrogenase, bilirubin and D-dimer, and lower levels of albumin and fibrinogen. They also required admission to the intensive care unit more frequently. Among patients tested, complement abnormalities and reduced ADAMTS13 activity were observed in 64.3% and 44.4% of cases, respectively. All patients received glucocorticoids. Treatment for TMA included plasma-exchange, eculizumab, and rituximab. Conclusions The possible coexistence of MAS and TMA in rheumatic diseases may be underrecognized. This association should be considered in patients with MAS who develop disproportionate anemia, thrombocytopenia, and lactate dehydrogenase increase, or have multiorgan failure.

Aim of the work: To describe and compare sleep disturbance in children and adolescents with inactive juvenile idiopathic arthritis (JIA) and to study their relation to health-related quality of life (HRQoL). Patients and methods: Fifty JIA patients and 50 controls along with their parents were studied. Sleep disturbance was assessed by the Children's Sleep Habits Questionnaire (CSHQ) and HRQoL was assessed according to the revised KINDLR questionnaire. Results: The 50 JIA children were 14 boys (28%) and 36 girls (72%); 58% children and 42% adolescent. The mean age of participants was comparable between boys (11.6 ± 2.9 years) and girls (11.4 ± 3.3 years) either in JIA (p = .76) or control (p = .56). Patients enrolled had enthesitis-related arthritis in 6(12%), RF-positive polyarthritis in 8(16%), oligoarthritis in 32(64%), systemic arthritis in 2(4%) and psoriatic arthritis in 2(4%). Patients had higher CSHQ score (45.5 ± 8.2) and a lower KINDLR (72.4 ± 16.8) compared to the control (40.4 ± 3.4 and 78.3 ± 5.4; p

Introduction: ABIRISK is a project funded by Innovative Medicine Initiative, with the aim to investigate anti-drug antibody (ADA) formation in the treatment of JIA with biologics (BPs). A major limitation to the use of biologics is the development of ADA that may decrease the efficacy of BPs. Objectives: The aim of this project is to improve the capability to predict biologic immunogenicity in JIA patients. Methods: JIA Patients (by ILAR criteria) followed by 24 PRINTO centres in 12 countries were prospectively enrolled and treated with Etanercept, Adalimumab or Tocilizumab. Patient’s data were obtained from Pharmachild, a pharmacovigilance data registry of JIA patients. For each patient detailed demographic and clinical information were reported; biologic samples were collected for PK and ADA detection before therapy start as well as at periodic visits up to month 18 of follow-up. Disease activity was assessed with Juvenile Arthritis Disease Activity Score-10 (JADAS10) and JIA American College of Rheumatology (JIA ACR) criteria. Results: 148 patients were included in the analysis. Five patients were considered twice because treated with 2 different sequential biologics. Demographic and clinical data by therapy are represented in the table. 54% of the patients were treated with Adalimumab. Disease duration was higher in the group receiving Tocilizumab. Disease activity showed a pattern of improvement over time both globally and for each treatment group (Table 1). Anti-adalimumab and antitocilizumab antibodies were detected respectively in 14 and 3 patients, while no patient developed antibodies anti-etanercept. Conclusion: Preliminary data show a global improvement of disease activity during follow-up period. Analysis of the correlation between drug concentration/ADA development and clinical information will help to determine which patients will respond best to which biologic.

Background:Juvenile Idiopathic Arthritis (JIA) patients experience impaired health and wellbeing due to multiple causes of physical and psychosocial distress, including treatment burden. Despite emerging evidence of its relevance [1], the contribution of treatment adverse events to patient-reported outcomes (PROs) in JIA has been poorly explored.Objectives:To evaluate and rank the impact of patient-reported adverse events (AEs) on overall wellbeing, health-related quality of life (HRQoL), school problems and self-reported medication adherence using data from Pharmachild, a large international JIA pharmacovigilance registry.Methods:Registry entries on 5340 prospective visits of 2251 patients enrolled till December 2018 were analyzed; all included patients were treated with at least one DMARDS or Biologic agent at the time of visit. In the Juvenile Arthritis Multidimensional Assessment Report (JAMAR), patients and parents compiled a checklist of treatments, side effects, self-reported adherence, administration difficulties and disease-related school problems occurred in the previous 4 weeks. Evaluated outcomes included patient acceptable symptom state (PASS), VAS-measured patient assessment of overall wellbeing (PGA) and HRQoL, assessed through the physical health (PhH) and psychosocial health (PsH) subscales. The relationships between AEs and PROs were tested through generalized linear models, accounting for disease activity and symptoms levels. Bayesian Networks were used to explore the causal effects of specific AEs on outcomes to disentangle the confounding role of disease status.Results:AEs were reported in 22.9% of visits. For similar levels of physician global assessment (MD global), patient-assessed disease activity, pain and function, patients reporting AEs had worse PGA, PsH, and lower probability of reaching PASS (fig. 1, all p-values 20.031) and appears to be mediated by effects on PsH and school problems (p Conclusion:AEs have a measurable effect on the wellbeing and psychosocial health of JIA patients, particularly when disease activity is low, and significantly affect school activity and medication adherence. Mood swings and sleep problems show the strongest influence on HRQoL. Addressing AEs appears important to reduce disease impact, improve patients’ satisfaction and therapeutic compliance.References: :[1]Weitzman, Elissa R., et al. Journal of patient-reported outcomes 2.1 (2018): 1.Acknowledgments:for the Paediatric Rheumatology International Trials Organisation (PRINTO)Disclosure of Interests: :Alessandra Alongi: None declared, Alessandro Consolaro Grant/research support from: Pfizer Inc., AlfaSigma, Speakers bureau: AbbVie, Gordana Vijatov-Djuric: None declared, Giovanni Filocamo: None declared, Olga Vougiouka: None declared, Alma Nunzia Olivieri: None declared, Cristina Herrera Mora: None declared, Wolfgang Emminger: None declared, Angelo Ravelli: None declared, 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

To the Editor: The optimal duration of treatment in patients with juvenile idiopathic arthritis, especially systemic JIA (sJIA), is a major concern for parents and physicians alike. Innovative medicines have managed to control this otherwise potentially life-threatening condition1. However, questions remain regarding the duration and the best timing for cessation of treatment. We report the results of a retrospective study describing the longterm outcome of children with sJIA treated with the antiinterleukin (IL)-1β monoclonal antibody canakinumab. In these children, treatment was discontinued following sustained clinical remission; we aim to identify potential relapse-associated risk factors. This was a single-center retrospective case study conducted from January 2008 to January 2017 and including patients with sJIA (based on International League of Associations for Rheumatology criteria)2 who had clinically inactive sJIA (clinical remission on medication/Wallace criteria)3 for at least 2 years with canakinumab. Patients were monitored for up to 4 years [median time 3.4 yrs, interquartile range (IQR) 2.4–3.7] following attempted canakinumab withdrawal (the study period began at the time of canakinumab withdrawal). Demographics, clinical, and laboratory variables were recorded at the study onset. We also collected data … Address correspondence to Dr. D. Maritsi, Infectious Diseases, Immunology and Rheumatology Unit, Second Department of Paediatrics, P. & A. Kyriakou Children’s Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. E-mail: dmaritsi{at}gmail.com

Background Robust scientific evidence on the safety and efficacy of certain vaccines in patients with rheumatic diseases is available; therefore guidelines regarding immunizations in this vulnerable group of children are published via a variety of official health organizations/societies including the Greek Rheumatology Society. Nonetheless, the uptake of specific immunizations is suboptimal. In Greece, vaccinations are mainly delivered by primary care Paediatricians. Objectives The purpose of this study was to describe the knowledge, attitude and current practice of General Paediatricians working in primary care regarding vaccination in children with rheumatic diseases on immunosuppressive medication across Greece and to identify barriers and facilitators that could be used to promote uptake. Methods This was a cross-sectional survey, conducted with an anonymous questionnaire of 25 items distributed to Paediatricians via an online platform. Data collected included demographics, questions on knowledge, perceptions and opinions as well as advice given to families. Additionally, questions addressed three specific categories: live-vaccines, non-live vaccines and annual influenza vaccine. This study was approved by the “P. & A. Kyriakou” Children’s Hospital Research and Ethics Committee. Results Out of 400 questionnaires sent out, 256 were returned. Mean age was 48 years age ((+/-8.2) mean duration of working as a Pediatrician was 15 years (+/-6.7). 25% of the responders worked in rural areas and the remaining in urban areas. 67% worked in the private sector. The majority (78%) of doctors felt that vaccination in children with rheumatic diseases is of pivotal importance. 50% gave specific advice on immunisations at initial diagnosis and 25% checked vaccination status at regular intervals. Responders were using a variety of guidelines in order to reach a clinical decision; still 45% were unaware of the existing national guidelines. 50% were hesitant to adhere to the national vaccination scheme without expert input. Reasons were: not convinced from current literature that the vaccine is safe (32%), afraid to cause disease flare (43%), unable to deal with parental concerns/refusal (54%). 12% of responders felt that the rheumatic disease may have been triggered by a vaccine. The majority (95%) were pro annual influenza vaccination, while a minority (15%) was against live vaccines administration even if the patient was not on immunosuppressive treatment. 75% of doctors were keener to administer booster doses rather than primary ones, whlie 75% of respondents would postpone vaccinations in all cases if disease was active. Conclusion Variation in opinion and clinical practice exists. Overall, although Greek Paediatricians are well informed regarding efficacy and side effects of immunizations, there are steps to be made form principle to practice. Further research will allow the development of clear guidelines to aid in the management of increasing numbers of children with rheumatic diseases. Acknowledgement None Disclosure of Interests None declared

Background Macrophage activation syndrome (MAS) is a severe complication of rheumatologic conditions, mainly systemic juvenile idiopathic arthritis (sJIA), and is classified as a secondary form of hemophagocytic lymphohistiocytosis (HLH). Thrombotic microangiopathy (TMA) is a heterogeneous group of potentially fatal diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury. The association between TMA and HLH has been described only in single reports in renal transplant recipients1 and in two cases of virus-induced HLH2. TMA associated with MAS has never been reported so far Objectives To present the preliminary data from a multinational cohort of pediatric patients with MAS and TMA Methods The clinical charts of patients with MAS were retrospectively reviewed to identify the instances that were associated with TMA. Demographic, clinical and laboratory features at MAS and TMA onset, therapeutic interventions and outcome were collected. Results A total of 14 patients, 71.4% females, with MAS and TMA were collected. An underlying rheumatologic disease was reported in 9/14 (8 sJIA or sJIA-like illness and 1 systemic lupus erythematosus). The median age at MAS onset was 8.6 years. In 5 patients MAS and TMA occurred simultaneously, whereas in 4 TMA preceded and in 5 followed MAS. The main features at MAS and TMA onset are presented in Table. Low complement levels and reduced ADAMTS13 activity were observed in 75% and 43% of patients respectively. For MAS management, 85.7% of patients received high-dose corticosteroids and 71.4% cyclosporine; in 5 cases anakinra was added. TMA episodes were treated with plasma-exchange in 57.1% of patients; 7 patients were given biologics (1 rituximab and 6 eculizumab) with good results. Admission to the Intensive Care Unit was required in 85.7% of cases. All patients survived. Conclusion The association of MAS and TMA is a life-threatening condition, likely under-recognized. Clues to suspect TMA in a patient with MAS are the increase in LDH and decrease in platelet count out of proportion of other laboratory abnormalities, the drop in haptoglobin level, the finding of schistocytes in blood smear and the new onset of hematuria. Biologics, particularly rituximab and eculizumab, may offer an adjunctive therapeutic option for refractory cases. References [1] Esmaili H, et al. An update on renal involvement in hemophagocytic syndrome. J Nephropathol 2016; 2Fraga-Rodriguez GM, et al. Eculizumab in a child with atypical haemolytic uraemic syndrome and haemophagocytic lymphohistiocytosis triggered by cytomegalovirus infection. BMJ Case Rep2017. Disclosure of Interests Francesca Minoia: None declared, Jessica Tibaldi: None declared, Valentina Muratore: None declared, Romina Gallizzi: None declared, Claudia Bracaglia: None declared, Alessia Arduini: None declared, Elif Comak: None declared, Olga Vougiouka: None declared, Ralf Trauzeddel : None declared, Giovanni Filocamo: None declared, Concetta Micalizzi: None declared, Angelo Ravelli Grant/research support from: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Consultant for: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche, Speakers bureau: Angelini, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Novartis, Pfizer, Reckitt Benkiser, and Roche

Made available in DSpace on 2019-10-05T16:54:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-04-01 IRCCS Istituto Giannina Gaslini Background To our knowledge, the characteristics and burden of childhood arthritis have never been studied on a worldwide basis. We aimed to investigate, with a cross-sectional study, the prevalence of disease categories, treatment methods, and disease status in patients from across different geographical areas and from countries with diverse wealth status. Methods In this multinational, cross-sectional, observational cohort study, we asked international paediatric rheumatologists from specialised centres to enrol children with a diagnosis of juvenile idiopathic arthritis, according to International League of Associations for Rheumatology criteria, who were seen consecutively for a period of 6 months. Each patient underwent retrospective and cross-sectional assessments, including measures of disease activity and damage and questionnaires on the wellbeing and quality of life of the children. We qualitatively compared the collected data across eight geographical areas, and we explored an association between disease activity and damage and a country's gross domestic product (GDP) with a multiple logistic regression analysis. Findings Between April 4, 2011, and Nov 21, 2016, 9081 patients were enrolled at 130 centres in 49 countries, grouped into eight geographical areas. Systemic arthritis (125 [33.0%] of 379 patients) and enthesitis-related arthritis (113 [29.8%] of 379) were more common in southeast Asia, whereas oligoarthritis was more prevalent in southern Europe (1360 [56.7%] of 2400) and rheumatoid factor-negative polyarthritis was more frequent in North America (165 [31.5%] of 523) than in the other areas. Prevalence of uveitis was highest in northern Europe (161 [19.1%] of 845 patients) and southern Europe (450 [18.8%] of 2400) and lowest in Latin America (54 [6.4%] of 849), Africa and Middle East (71 [5.9%] of 1209), and southeast Asia (19 [5.0%] of 379). Median age at disease onset was lower in southern Europe (3.5 years, IQR 1.9-7.3) than in other regions. Biological, disease-modifying antirheumatic drugs were prescribed more frequently in northern Europe and North America than in other geographical settings. Patients living in countries with lower GDP had greater disease activity and damage than those living in wealthier countries. Damage was associated with referral delay. Interpretation Our study documents a variability in prevalence of disease phenotypes and disparities in therapeutic choices and outcomes across geographical areas and wealth status of countries. The greater disease burden in lowerresource settings highlights the need for public health efforts aimed at improving equity in access to effective treatments and care for juvenile idiopathic arthritis. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Univ Genoa, Ist Giannina Gaslini, IRCCS, Clin Paediat & Rheumatol, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Epidemiol & Biostat Serv, Genoa, Italy Univ Genoa, Ist Giannina Gaslini, IRCCS, Sci Directory, Genoa, Italy Univ Genoa, PRINTO, IRCCS, Ist Giannina Gaslini, Genoa, Italy Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy Wilhelmina Childrens Hosp, Dept Pediat Immunol & Rheumatol, Utrecht, Netherlands Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India Univ Hosp 12 Octubre, Dept Pediat Rheumatol, Madrid, Spain Alfaisal Univ, Dept Pediat Rheumatol, King Faisal Specialist Hosp, Riyadh, Saudi Arabia Alfaisal Univ, Res Ctr, Riyadh, Saudi Arabia Western Univ Childrens Hosp, Hlth Sci Ctr, London, ON, Canada Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway Oslo Univ Hosp, Med Fac, Oslo, Norway Univ Oslo, Oslo, Norway Oslo Univ Hosp, Norwegian Natl Advisory Unit Rheumat Dis Children, Oslo, Norway Univ Hosp Munster, Dept Pediat Rheumatol & Immunol, Munster, Germany Hosp Sor Maria Ludovica, Rheumatol Serv, La Plata, Buenos Aires, Argentina Bucharest Emergency Hosp, Cluj Napoca, Romania Childrens Emergency Hosp, Cluj Napoca, Romania Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA Alberta Childrens Prov Gen Hosp, Div Pediat Rheumatol, Dept Pediat, Calgary, AB, Canada Sofiamed, Pediat Dept, Sofia, Bulgaria Rigshosp, Juliane Marie Ctr, Paediat Rheumatol Unit, Copenhagen, Denmark Natl Inst Rheumatism & Physiotherapy, Clin Immunol Adult & Paediat Rheumatol Dept, Budapest, Hungary Univ Latvia, Pediat Dept, Riga, Latvia Univ Latvia, Univ Childrens Hosp, Riga, Latvia Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil Shariati Hosp, Rheumatol Res Ctr, Dept Pediat & Rheumatol, Tehran, Iran Inst Rheumatol Belgrade, Div Pediat Rheumatol, Belgrade, Serbia Thessaloniki Univ, Dept Pediat 1, Hippokrat Gen Hosp, Sch Med, Thessaloniki, Greece Univ Estadual Paulista, Botucatu Fac Med, Botucatu, SP, Brazil

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Greek language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographics, clinical data, and the JAMAR from 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach’s alpha, interscale correlations, test–retest reliability, and construct validity (convergent and discriminant validity). The Greek JAMAR was fully cross-culturally adapted with two forward and three backward translations. A total of 272 JIA patients (5.9% systemic, 57.7% oligoarticular, 21.3% RF negative poly-arthritis, 15.1% other categories), and 100 healthy children were enrolled in all centres. The JAMAR components discriminated well-healthy subjects from JIA patients; notably, there was no significant difference between healthy subjects and their affected peers in psychosocial quality of life and school-related items. All JAMAR components revealed good psychometric performances. In conclusion, the Greek version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and in clinical research.

Objective.To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.Methods.International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.Results.A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide.Conclusion.The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.

OBJECTIVE: To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis. STUDY DESIGN: The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples. RESULTS: Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from 99% for a score of =123. A cutoff value of =60 revealed the best performance in discriminating pHLH from MAS. CONCLUSION: The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

Objective To develop criteria for the classification of macrophage activation syndrome (MAS) in patients with systemic juvenile idiopathic arthritis (JIA). Methods A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of 28 experts was first asked to classify 428 patient profiles as having or not having MAS, based on clinical and laboratory features at the time of disease onset. The 428 profiles comprised 161 patients with systemic JIA-associated MAS and 267 patients with a condition that could potentially be confused with MAS (active systemic JIA without evidence of MAS, or systemic infection). Next, the ability of candidate criteria to classify individual patients as having MAS or not having MAS was assessed by evaluating the agreement between the classification yielded using the criteria and the consensus classification of the experts. The final criteria were selected in a consensus conference. Results Experts achieved consensus on the classification of 391 of the 428 patient profiles (91.4%). A total of 982 candidate criteria were tested statistically. The 37 best-performing criteria and 8 criteria obtained from the literature were evaluated at the consensus conference. During the conference, 82% consensus among experts was reached on the final MAS classification criteria. In validation analyses, these criteria had a sensitivity of 0.73 and a specificity of 0.99. Agreement between the classification (MAS or not MAS) obtained using the criteria and the original diagnosis made by the treating physician was high (κ = 0.76). Conclusion We have developed a set of classification criteria for MAS complicating systemic JIA and provided preliminary evidence of its validity. Use of these criteria will potentially improve understanding of MAS in systemic JIA and enhance efforts to discover effective therapies, by ensuring appropriate patient enrollment in studies.

Juvenile sarcoidosis is a rare, chronic, multisystem, granulomatous disease of obscure etiology which is seen in childhood and adulthood. The disease in childhood has a course different from that in adulthood.PubMed database was searched using terms sarcoidosis, children or childhood sarcoidosis or juvenile sarcoidosis in combination with one of the following terms: epidemiology, clinical manifestations, genetics, diagnosis, treatment, and prognosis. We also retrieved the terms such as early onset sarcoidosis and Blau syndrome. Furthermore, e-medicine and European Respiratory Society monographs for sarcoidosis were reviewed.Sarcoidosis in childhood presents with two age dependent, distinct forms. In younger children it is clinically evident before the age of four years and characterized by the triad of rash, arthritis and uveitis. In their older counterparts, the juvenile late onset sarcoidosis involves several organs and its clinical appearance resembles the adult type of the disease, with the respiratory system being most frequently affected (hilar lymphadenopathy, pulmonary infiltrations). Steroid is the main agent of treatment whereas methotrexate is also used for beneficial steroid sparing effects. New, novel therapies may change the outcome of the disease especially in difficult morbid cases.Sarcoidosis in childhood is recognized as a systemic disease affecting various organs and having diverse clinical course depending on the age of onset.

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR.

We report on the development of steroid-refractory recurrent cytopenias in a child with 22q11.2 deletion syndrome. His first hematological complication was autoimmune hemolytic anemia at 3 months of age. Thereafter, he developed severe autoimmune cytopenias of all 3 hematological lineages with poor response to steroids and intravenous immunoglobulin. At the age of 2½ years, a course of anti-CD20 therapy (Rituximab) was given with transient hematological recovery. Because of persistent symptoms, bone marrow transplantation from a matched unrelated donor was performed. Although the data in the use of anti-CD20 therapy in children with 22q11.2 deletion syndrome and autoimmune cytopenias are limited, our experience suggests its potential benefit.

Background The main therapeutic goals that can determine success of biologic treatment in systemic juvenile idiopathic arthritis (SJIA) include achieving and maintaining clinical remission, controlling disease activity and tapering corticosteroids (CS). Canakinumab (CAN) has been shown to improve several of these parameters in previous studies 1 . However, little is known about SJIA patients (pts) using CAN long-term. Objectives To evaluate the efficacy, safety and long-term treatment response of CAN treatment-naive pts with active SJIA. Methods This was an open-label, non-comparative study (NCT00891046) of CAN-naive SJIA pts (age ≥2 - 6 Mo) and changes in JADAS-CRP (Juvenile Arthritis Disease Activity Score- C-reactive protein) scores over time. Safety was assessed by adverse events (AEs) and serious AEs (SAEs) reports. Results A total of 123 pts with active SJIA were enrolled of whom 70 (57%) pts had fever and 71 (57.7%) pts used CS at BL. Mean CRP was 117.8 mg/L (normal: 0–10mg/L) and, on average, pts had, 9.9 active joints and 8.9 joints with limited motion. A rapid response was observed at Day 15, 59 (51%) with aACR ≥70 responses and 27 (26%) having aACR 100 responses. These responses increased and were maintained at subsequent time points (Table). Overall, 73.0% of pts had ID on at least 1 visit. At 6th month, clinical remission was achieved in 52 (42.3%) pts and 33 (26.8%) pts had clinical remission for at least 12 consecutive months. At BL, the median JADAS10-CRP score was 22.3 (indicating high disease activity), with median changes from BL of -12.0 at Day 15 and -16.8 at last assessment indicating moderate and low disease activity, respectively. At the last assessment, 59 (48.4%) pts were rated as ID (JADAS 1 and Conclusions In this long-term study, CAN treatment was associated with rapid response and sustained therapeutic effect over the long-term in the naive pts with active SJIA. The safety profile is consistent with other CAN studies. References Ruperto et al. N Engl J Med. 2012;367:2396–406. Disclosure of Interest N. Ruperto Grant/research support from: BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi and Merck Serono funded The Gaslini Hospital for the research activities of the hospital in a fully independent manner besides any commitment with third parties, Consultant for: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, Speakers bureau: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, H. Brunner Consultant for: Novartis, Genentech/Roche, BMS, Pfizer, Astrazeneca, Jannsen, Tekada, Biogen, BAXALTA, Speakers bureau: Novartis, Genentech/Roche, P. Quartier Grant/research support from: Abbvie, Novartis, Pfizer, Roche, Consultant for: Abbvie, Novartis, Sobi, Speakers bureau: Abbvie, BMS, Novartis, Pfizer, Roche, Sobi, T. Constantin Consultant for: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, Speakers bureau: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Pfizer, I. Kone-Paut Grant/research support from: Grant/research support to my institution: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, CHUGAI, Abbvie, K. Marzan Grant/research support from: Novartis and Abbvie, N. Wulffraat Grant/research support from: Sobi, AbbVie, Consultant for: Novartis, Pfizer, R. Schneider Consultant for: Novartis, Roche, Sobi, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: Unrestricted grant support GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich Speakers bureau: Novartis, B. Lauwerys: None declared, E. Haddad Grant/research support from: Unrestricted Institutional Educational Fund, E. Nasonov: None declared, M. Trachana Grant/research support from: Pfizer, O. Vougiouka Grant/research support from: Novartis, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Employee of: Novartis, A. Martini Grant/research support from: Abbott, Bristol Myers and Squibb, Francesco Angelini S.P.A., Glaxo Smith & Kline, Janssen Biotech Inc Novartis,Pfizer Inc,Roche,Sanofi Aventis and Schwarz Biosciences GmbH funded Gaslini Institute for the PRINTO research activities, Consultant for: Bristol Myers and Squibb, Janssen Biotech Inc,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis and Schwarz Biosciences GmbH Biosciences GmbH funded Gaslini Institute for the PRINTO research activities, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech

Background SJIA is a distinct and debilitating form of arthritis associated with elevated cytokine (interleukin [IL]-1 and IL-6) levels. 1 Studies have shown that biologics (IL-1 and IL-6 inhibitors), including canakinumab (CAN), a selective, human anti-IL-1β monoclonal antibody, are more effective than conventional medications (NSAIDs, corticosteroids, methotrexate) in the treatment of SJIA patients (pts). 1,2 However, little is known about long-term efficacy and safety of biologics in SJIA. Objectives To assess long-term efficacy and safety of CAN treatment in a 5-year (yr) follow-up of SJIA pts. Methods This was an open-label extension study of SJIA patients participating in the clinical trials of CAN, with details reported earlier. 3 Pts (age, 2–20 yrs) received subcutaneous (sc) CAN (4 mg/kg) every 4 wks. Baseline is defined as the starting point of the extension trial. Efficacy measurements were done every 3 months including adapted paediatric response criteria (aACR), clinical inactive disease, clinical remission on medication (12 months of continuous clinical inactive disease) and juvenile arthritis disease activity score (JADAS). Safety was assessed monthly. Results Overall, 147 pts had a median treatment duration of 3.2 yrs, and 82 (56%) were exposed to CAN for >3 yrs (total treatment exposure of ∼365 pt-yrs). At 3 month of CAN therapy, 50% of pts had inactive disease, increasing to 49% at last assessment. Of the 107 pts with an aACR 30 at entry to the extension, 61.7% had aACR 100, with 86.0%, 87.9% and 91.6% having aACR 70/50/30 responses, respectively at last assessment. Clinical remission on medication was achieved in 43.0% of pts. Median JADAS10-CRP at baseline was 8.2 (indicating moderate disease activity), and at last assessment, median change from baseline was −0.2, with a median score of 1.8, indicating low disease activity, with similar results noted for JADAS27-CRP. Most common adverse event (AE) was infection (2.0 infections/100 pyr) typically involving the upper respiratory tract. Overall, 47 (32.0%) pts had >1 serious AE (SAE; mostly infections, macrophage activation syndrome [MAS] or SJIA flare), 10 cases of MAS (43.8 events/100 pyr) were reported, and 18 (12.2%) pts discontinued due to an AE. No deaths were reported. Conclusions In patients previously treated with CAN in pivotal trials, response to treatment was sustained or improved during long-term treatment in the extension study. Safety profile of CAN was consistent with safety findings from previous studies. References Ruperto N, et al. N Engl J Med. 2012;367:2396–406. Ringold S, et al. Arthhritis & Rheum. 2013;65(10):2499–512. Ruperto N, et al. Ann Rheum Dis. 2015;74(2):608. Disclosure of Interest N. Ruperto Grant/research support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Speakers bureau: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, Vertex, H. Brunner Consultant for: Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK, BMS, Speakers bureau: Novartis, Roche, P. Quartier Grant/research support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, T. Constantin: None declared, E. Alexeeva Grant/research support from: Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb, Centocor, Speakers bureau: Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac, Pfizer, R. Schneider Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, I. Kone-Paut Grant/research support from: SOBI, Novartis, Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Roche/Chugai, K. Schikler Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, K. Marzan Grant/research support from: Novartis, Abbvie, N. Wulffraat Grant/research support from: Novartis, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich: None declared, B. Lauwerys: None declared, E. Haddad: None declared, E. Nasonov: None declared, M. Trachana Grant/research support from: Novartis, Abbvie, Bristol Meyers, Consultant for: Novartis, Roche, Pfizer, O. Vougiouka: None declared, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Speakers bureau: Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, Takeda, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech, Roche, Novartis

Results Ocular symptoms were unresponsive to treatment with local and systemic steroids, methotrexate plus cyclosporine in all patients. One child had also received etanercept for 2.5 years with poor response. Due to frequent relapses of uveitis (especially when tapering local steroids) we commenced treatment with adalimumab (24mg/m of body surface sc/14 days), while cyclosporine was withdrawn. The mean duration of uveitis until then was 27 months and the mean age of patients at the initiation of treatment was 7.3 years. All patients had at least one complication of uveitis (synechiae: 2 children, band keratopathy: 2 children, cystoid macular edema: 2 children, cataract: 1 child, glaucoma: 2 children). The mean duration of adalimumab treatment was 4.5 months. No side effects were observed. During adalimumab treatment uveitis subsided in all patients with no recurrence neither requiring local treatment. Methotrexate was reduced to the lower dose of 7.5 mg/wk.

Materials The boy was referred to our department with right retrobulbal pain and bilateral papilledema, while brain MRI was normal. Physical examination revealed faint left radial pulse, non palpable left femoral artery, and hypertension, with right hand blood pressure 162/64 mmHg, in a difference with left hand blood pressure 128/70 mmHg. Bruits were auscultated all over the chest (precordium, supraclavicular, axillary and scapular area).

Background/Purpose: In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR. The aim of this study was to evaluate the degree of IR among children with systemic juvenile idiopathic arthritis (sJIA) and to determine whether treatment with tocilizumab (TCZ) results in attenuation of IR in sJIA. Methods: Patients from TENDER[1] were included if baseline and week 6 fasting insulin were measured. Glucocorticoid tapering was not permitted until week 6. Insulin sensitivity was quantified using the homeostatic model of insulin resistance (HOMA-IR). Patients were classified as having IR if their HOMA-IR was ≥2.2 U. Change in HOMA-IR after 6 weeks was assessed using paired t-test. Baseline associations with HOMA-IR and factors predicting change of HOMA-IR from baseline were assessed using regression analyses. Factors changing in association with HOMA-IR change were assessed. Results: Ninety-two patients with sJIA were analyzed. 62 were randomly assigned to TCZ and 30 to placebo, 12 of whom required escape therapy with TCZ by week 6. At baseline, 40 patients (43%) had IR. Baseline HOMA-IR was associated with higher standardized body mass index and higher IL-6 levels (β-coefficients [95% CI]: 0.20 [0.05, 0.35] and 0.019 [0.001, 0.038], respectively) but not with JADAS, CRP, active joint count, or presence of fever. Of the 74 patients who received TCZ, 34 (46%) had IR at baseline, including 4 patients who escaped from the placebo arm, compared with 6/18 (33%) who received only placebo. IR patients treated with TCZ but not placebo had significant reductions in HOMA-IR at week 6 (1). Across all IR patients, improvement in JADAS and active joint count was not associated with improvement in HOMA-IR (β-coefficients [95% CI]: 0.04 [−0.07, 0.14] and 0.08 [−0.06, 0.22], respectively). Table 1. Change in HOMA-IR After 6 Weeks of TCZ Treatment in Children With sJIA in the TENDER Study Change in HOMA-IR Mean (95% CI) pa a NS, not significant; PBO, placebo. aPaired t-test. TCZ (n = 34) −0.2 (−3.8, −0.2) 0.03 PBO (n = 6) 0 (−1.7, 1.6) NS Conclusion: After only 6 weeks of TCZ treatment, HOMA-IR was improved in IR patients with sJIA in the presence of unchanged glucocorticoid dose. These data support a mechanistic contribution of IL-6 to IR in vivo in humans.

Background Canakinumab (CAN) leads to improvement for patients (pts) with systemic juvenile idiopathic arthritis (SJIA) 1 . However, little is known about potential differences in response to CAN treatment between pts with vs. without SJIA associated fever at the time of the first CAN administration. Objectives To evaluate the long-term efficacy and safety profile of CAN-naive children with SJIA pts with and without SJIA associated fever. Methods Pts aged 2-20 yrs with SJIA with and without SJIA associated fever at enrollment received open-label CAN 4mg/kg s.c. every 4 wks. Every 3 months, response to CAN was measured by adapted JIA ACR response criteria (aACR/JIA); juvenile arthritis disease activity score [JADAS]; clinical inactive disease; clinical remission on medication [6 months continuous clinical inactive disease]. Safety was assessed monthly. Results Data on 122/267 pts, 53 (43%) with and 69 (57%) without SJIA associated fever, were available for analysis with a median 94 wk study duration. At Wk4, ∼75% of both subgroups had responded (≥aACR/JIA30), increasing to 90% at Wk12. At Wk2, ∼21% of both subgroups had inactive disease; 44% at Wk8; 60% at Wk20 and then 60-70% for the remainder of the trial. Clinical remission on medication was achieved in about 29% of pts in both subgroups with ∼22% maintaining it for ≥12 consecutive months. At baseline, the median JADAS score was 21.5 with 8 (7.5%) and 99 (92.5%) pts meeting the criteria for moderate (JADAS >3.8 and ≤10.5) and high disease activity (JADAS >10.5), respectively. At Day15, the median JADAS was 6.8 and 1.5 at the last assessment. In addition, at the last assessment, 53 (48%) pts were rated as inactive disease (JADAS ≤1); 10 (9%) with low active disease activity (JADAS >1 and ≤3.8); while 14 (13%) had moderate and 31 (28%) with high disease activity. A similar long-term safety profile to the pivotal program in children with fever at enrollment was observed in these CAN-naive pts with or without fever. The most common type of adverse event (AE) reported was infection (0.56 infections/100 PT-days) typically involving the upper respiratory tract. Fifteen pts discontinued due to an AE and 40 had >1 SAE (mostly infections, macrophage activation syndrome [MAS], or flare-associated) and no deaths. Eight cases of MAS (0.013 events/100 pt-days) were reported. Conclusions Canakinumab provides similar efficacy (inactive disease, clinical remission) in SJIA pts with and without SJIA associated fever at treatment onset. The long-term safety profile was acceptable and similar to the pivotal program in SJIA children with fever at enrollment. References Ruperto et al. N Engl J Med. 2012; 367: 2396-406. Disclosure of Interest N. Ruperto Grant/research support from: Abbott, Bristol Myers and Squibb, Francesco Angelini S.P.A., Glaxo Smith & Kline, Janssen Biotech Inc Novartis,Pfizer Inc, Roche,Sanofi Aventis,Schwarz Biosciences GmbH: I declare that the GASLINI Hospital which is the public Hospital where I work as full time employee has received contributions to support the research activities of the network of PRINTO, Consultant for: Bristol Myers and Squibb, Centocor Research & Development,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, I declare that the Gaslini Hospital which is the public Hospital where I work as full time employee has received contributions to support the PRINTO research activities from the industries above mentioned, Speakers bureau: Abbott, Abbvie, Amgen, Astellas, Biogenidec, Boehringer, Bristol MyersSquibb, Celgene, CrescendoBio, EMD Serono, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Reumatic.com, Roche, Sanofi, Servier, Sinergie, Takeda, H. Brunner Consultant for: Novartis, Genentech, Pfizer, UCB, AstraZeneca, Biogen, Boehringer-Ingelheim, Regeneron, Speakers bureau: Novartis, Genentech, P. Quartier Grant/research support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, T. Constantin Consultant for: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, Speakers bureau: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp &Dohme, Abbott, Bristol-Myers Squibb, Medac, Novartis, Pfizer, I. Kone-Paut Grant/research support from: To my institution: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, CHUGAI, Abbvie, K. Marzan Grant/research support from: Novartis and Abbvie, Employee of: University of Southern California, N. Wulffraat Grant/research support from: Novartis, Pfizer, Abbvie, SOBI, Consultant for: Novartis, Pfizer, SOBI, R. Schneider Consultant for: Novartis, Roche, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: Unrestricted grant support GSK, Novartis, Roche, J. Kummerle Deschner Grant/research support from: Novartis, Consultant for: Novartis, T. Kallinich Speakers bureau: Novartis, BMS and Pfizer, B. Lauwerys: None declared, E. Haddad: None declared, E. Nasonov: None declared, M. Trachana Grant/research support from: Abbvie, Novartis, Pfizer, Consultant for: Novartis, Pfizer, Roche, Speakers bureau: Novartis, Pfizer, Roche, O. Vougiouka Grant/research support from: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, K. Leon Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support from: The Gaslini Hospital, which is the public Hospital where I work as a full time employee, has received contributions to support the research activities of the network of PRINTO from Bristol Myers and Squibb, Glaxo Smith & Kline, Janssen Biotech Inc, Novartis, Pfizer, Roche, Schwartz Bioscences GmbH, Speakers bureau: AbbVie, Boerhinger, Celgene, CrescendoBio, Janssen, Meddimune, Novartis, NovoNordisk, Pfizer, Sanofi Aventis, Vertex, Servier, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech, Roche, Novartis

Background Hepatitis A is an indolent disease with a varying clinical spectrum and consequences. Little is known about the immune response to hepatitis A virus (HAV) vaccination, in children auto-inflammatory disorders including SoJIA. Objectives To assess the sero-protective efficacy and safety of immunization against hepatitis A in patients with auto-inflammatory disorders on treatment, not previously exposed to HAV, and compare this to healthy controls. Methods Matched case control study including patients with FMF, HIDS, FCAS and SoJIA and controls. All subjects received two doses of the inactivated anti-HAV vaccine at 0 and 6 months. Seroconversion and seroportection rates and anti-HAV IgG antibodies were assessed at enrollment, one month after the first dose and at one and 12 months after the last dose. Exclusion criteria were infection or disease flare concomitant or up to four weeks prior to immunization, recent steroid use (dose>0.5mg/kg/day), known liver disease or immunodeficiency, and serum testing positive for HAV infection. Clinical and demographic data as well as medications used were collected for each patient. Onset of typical disease symptoms within two weeks from immunization was considered as a flare. Results Twenty-eight patients with a mean age of 5.3 years completed the study; 13 (46%) had SoJIA, 13 (46%) had FMF, one had HIDS and one had FCAS. Thirteen (46%) patients received colchicine, 12 (42%) received methotrexate and 10 (35.7%) received steroids while 7 (25%) were on biologics. The control group consisted of 76 healthy individuals (mean age 4.75 years). At four weeks after primary vaccination, 75% of patients and 77.6% (p=0.4) of the controls attained seroprotection. Ninety-two percent and 100% of the patients while 96.1% and 96.1% (P=0.3) of the controls maintained their antibody status four weeks and 52 weeks after the second dose respectively. Seroconversion rates were 90.8%,98.7% and 98% for the patient group and 92.8%,100%, 100% for the controls at 4 weeks after the first dose, and four and 52 weeks after the second dose. Mean IgG concentration at 4 weeks was 52.7mIU/ml in the patient and 96.2mIU/ml in the control group (t-test, p=0.003) while it reached 131mIU/ml and 218mIU/ml after the second dose respectively (p=0.001). At 18 months mean IgG concentration was 164 mIU/ml in the patient group and 245 mIU/ml in the control group (p=0.002). Subgroup analysis showed that only 72% patients on DMARDS (MTX=/-biologics) achieved seroprotection after the initial vaccine dose, compared to 92.4% of patients on colchicine, however numbers were small to reach statistical significance.Patients with FMF mounted a better immune response compared to SoJIA patients at all time points [74.5IU/ml vs 36.5IU/ml (p=0.046), 172IU/ml vs 99IU/ml (p=0.015), 210IU/ml vs 129 IU/ml (p=0.015) Kolmogorov-Smirnof test]. Three patients developed a flare (1 HIDS and 2 FMF). Vaccines were well tolerated in the other patients. Mild adverse events were noticed in 6/28 (21.4%) patients and 15/76 (19.7%) controls. Conclusions Two doses of HAV vaccine are safe and effective in the majority of children with autoinflammatory disorders. Systemic illness should not preclude from completion of the vaccination schedule in cases where immunization against Hepatitis A is mandatory. However, based on our small cohort, there seems to be a significant possibility of flare. Disclosure of Interest None declared

Background Targeted treatments are becoming the mainstay for many autoinflammatory diseases, including the systemic juvenile idiopathic arthritis (sJIA). Canakinumab (CAB), a fully human anti-interleukin-1β (IL-1β) antibody, has recently been shown to be effective in refractory sJIA patients. Experience on the safety and efficacy of this treatment is still limited and completely lacking for Greek children with sJIA. Objectives To assess the efficacy and safety of CAB administration in Greek children with sJIA. Methods The recorded demographic, clinical, lab data were retrieved from the recently established “National Registry for sJIA under CAB”. Response was assessed according to the adapted American College of Rheumatology (ACR) pediatric criteria 1, 3, 6 and 12mos post-treatment. Results Six children (M:F 3:3) from different country regions, aged 4-16.4 years, all with a systemic disease course have been recorded in the Registry so far. Four pts were previous non responders to Methotrexate (MTX) +prednisolone (PDN) and 2 of them were additionally receivers of etanercept (1/4) or anakinra (1/4) prior to CAB. The remaining 2 pts were either non compliant to anakinra (1) or steroid dependent (1). Their disease duration prior to CAB treatment was 0.6- 16.2 yrs (median 7.66). All pts received the drug within the 1st to 7th mo after their flare (median 1mo), 5/6 have completed a follow-up period of 12mo to date while the remaining one, 8mo. CAB was administered (4mg/kg/mo, sc) together with PDN (6/6), plus MTX (5/6) or Leflunomide (1/6). At baseline, the systemic features were fever (6/6), rash (4/6), lymphadenopathy (2/6) and serositis (1/6). The range of active joints was 0-12 (median 2) and of the CRP 4-195mg/dL (median 71, cut off value ≤5). All pts responded to CAB without any adverse events; 5/6 achieved disease remission 1mo post-treatment, and the other one in the 3rd mo. Fever disappeared in 5/6 pts after the first drug administration and in the other one after the 3rd mo, while the rest systemic features, 1st mo post-treatment. The 6 pts achieved the following post-treatment ACRped 30/50/70/100 scores: 1st mo 2/0/1/3, 3rd mo 0/2/1/3, 6th mo 0/1/2/3 and 12th mo 0/1/1/3. 4/6 pts were able to discontinue PDN within the first to 6th mo, 1pt achieved a 20% PDN reduction and the latter one is still under PDN, but in clinical remission. No correlation was found between the level of ACRpedi and the disease duration prior to CAB administration for any time point of the study. Conclusions CAB was well tolerated by all 6pts, had a steroid sparing effect and a rapid efficacy in the vast majority of them. This on-going registry will be enriched and will follow-up all CAB recipients in a long-term base. References Ruperto N, Quartier P, Wulffraat N et al. A phase II study to evaluate dosing and preliminary safety and efficacy of canakinumab in systemic juvenile idiopathic arthritis with active systemic features.Arthritis Rheum. 2011 Sep 27. doi: 10.1002/art.33342. [Epub ahead of print] Disclosure of Interest M. Trachana Grant/Research support from: Abbott/Novartis/Pfizer, P. Pratsidou-Gertsi Grant/Research support from: Abbott/Novartis/Pfizer, O. Vougiouka: None Declared

Since the incidence of benign hypermobility syndrome is significantly high in otherwise healthy children, paediatricians should consider this benign entity when they evaluate musculoskeletal complaints in childhood.

Methods Patient data were collected retrospectively by pediatric rheumatologists (PR) or pediatric hemato-oncologists (PHO). Clinical features, treatments and outcome were compared between groups by Mann-Whitney or chisquare tests. “Severe course” was defined as ICU admission or death. Results 362 patients with MAS in sJIA were collected by 95 investigators from 33 countries. 179 patients (49.4%) were enrolled in Europe (EU), 72 (19.9%) in North America (NA) and 111 (30.7%) in other continents (OC). 79 (21.8%) patients were included by PHO. HP was detected in 44% of patients and was not detected or looked for in 56%. Severe course was reported in 92 (25%) patients. Comparison by geographic origin showed a lower frequency of CNS disease in EU patients. NA physicians used more frequently ivIg and biologics. Patients entered by PHO had greater frequency of multiorgan failure and were given more commonly biologics and etoposide, whereas PR used more frequently cyclosporine (CsA). Patients with HP had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen and received more frequently CsA, ivIg and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, greater frequency of haemorrhages and CNS dysfunction, lower levels of ESR, albumin and fibrinogen, higher levels of LDH and D-dimer and were treated more commonly with CsA, ivIg and etoposide. Conclusion

methotrexate and 27 received both. The control group consisted of 76 healthy individuals (mean age 5.2 years). At four weeks after primary vaccination 48% of patients and 65% (P