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ObjectivesRecent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations.MethodsRecommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD. After a systematic literature review, separate recommendations were formulated for paediatric and adult patients. For pedAIIRD, six overarching principles and seven recommendations were formulated and provided with the level of evidence, strength of recommendation and Task Force level of agreement.ResultsIn general, the National Immunisation Programmes (NIP) should be followed and assessed yearly by the treating specialist. If possible, vaccinations should be administered prior to immunosuppressive drugs, but necessary treatment should never be postponed. Non-live vaccines can be safely given to immunosuppressed pedAIIRD patients. Mainly, seroprotection is preserved in patients receiving vaccinations on immunosuppression, except for high-dose glucocorticoids and B-cell depleting therapies. Live-attenuated vaccines should be avoided in immunosuppressed patients. However, it is safe to administer the measles–mumps–rubella booster and varicella zoster virus vaccine to immunosuppressed patients under specific conditions. In addition to the NIP, the non-live seasonal influenza vaccination should be strongly considered for immunosuppressed pedAIIRD patients.ConclusionsThese recommendations are intended for paediatricians, paediatric rheumatologists, national immunisation agencies, general practitioners, patients and national rheumatology societies to attain safe and effective vaccination and optimal infection prevention in immunocompromised pedAIIRD patients.

Background:People with rheumatic diseases may be at increased risk of contracting COVID-19 due to their rheumatic disease or immunosuppressive treatments. It is currently unclear what the COVID-19 disease burden is for these people and whether any of their personal or disease characteristics are associated with contracting COVID-19.Objectives:To explore the proportion of, and characteristics associated with, contracting COVID-19 in children and young people (CYP) with rheumatic diseases and adults with rheumatic diseases from March 2020 to December 2020 during the COVID-19 pandemic.Methods:CYP and adults recruited to the international COVID-19 European Patient Registry, a parent-led, online, self-referred prospective cohort recruiting participants from around the globe, were included in current study if enrolled between 20th March 2020 and 30th December 2020. Demographic information was collected at enrolment and rheumatic disease, diagnoses of COVID-19 and lifestyle factors were collected at weekly intervals.The proportion of CYP and adults diagnosed with COVID-19 were assessed separately. Associations between contraction of COVID-19 at any point over follow-up and participant demographics, rheumatic disease and lifestyle factors at enrolment were assessed descriptively and via Mann-Whitney U-tests, Chi-squared tests and Fisher’s exact tests.Results:Within 642 CYP and 3646 adults, the majority were female (67%, 89%) and most commonly from the UK (43%, 82%), respectively. The most frequent diagnoses were polyarticular JIA (37%) in the CYP cohort and RA in the adults (63%). Comorbidities were common (45%, 61%) and the majority were taking one or more immunosuppressive therapies (88%, 92%), respectively. At the time of enrolment, 51% and 54% were practising social distancing, respectively.In both cohorts ~3% contracted COVID-19 at some point during follow-up (n=18 (2.8%) in CYP and n=103 (2.8%) in the adult cohort).In CYP, those who contracted COVID-19 were older (no COVID, median: 10, IQR: 7, 13, vs COVID, median: 14, IQR: 12, 16, pIn the adult cohort, those contracting COVID-19 were more commonly from Russia (no COVID: 2%, COVID: 14%) and less commonly from the UK (no COVID: 82%, COVID: 71%, pConclusion:A low proportion of CYP and adults with rheumatic diseases contracted COVID-19 in the 9 months since March 2020. However, given the self-reported nature of the survey and limited testing available across many countries, this study may underestimate the true burden of COVID-19 in the rheumatic disease community. Factors associated with COVID-19 differ between CYP and adults, with age and type of rheumatic disease associated in CYP and gender, kidney comorbidity and social distancing associated in adults.Acknowledgements:The authors thank all of the participants and families involved in the international COVID-19 European Patient Registry, as well as administrators. We also thank the team of volunteers who helped translate the surveys. We also thank ENCA, PRES and representatives from the international rheumatology community for their expertise and support.Disclosure of Interests:Stephanie Shoop-Worrall: None declared, Suzanne Verstappen: None declared, Wendy Costello: None declared, Saskya Angevare: None declared, Yosef Uziel: None declared, Carine Wouters: None declared, Nico Wulffraat Speakers bureau: Sobi, Grant/research support from: AbbVie, Richard Beesley: None declared

ObjectivesJuvenile idiopathic arthritis (JIA) is the most common class of childhood rheumatic diseases, with distinct disease subsets that may have diverging pathophysiological origins. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed.MethodsHere we profiled the adaptive immune system of 85 patients with JIA and 43 age-matched controls with indepth flow cytometry and machine learning approaches.ResultsImmune profiling identified immunological changes in patients with JIA. This immune signature was shared across a broad spectrum of childhood inflammatory diseases. The immune signature was identified in clinically distinct subsets of JIA, but was accentuated in patients with systemic JIA and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and patients with JIA, machine learning analysis of the data set proved capable of discriminating patients with JIA from healthy controls with ~90% accuracy.ConclusionsThese results pave the way for large-scale immune phenotyping longitudinal studies of JIA. The ability to discriminate between patients with JIA and healthy individuals provides proof of principle for the use of machine learning to identify immune signatures that are predictive to treatment response group.

Objective To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA). Methods Patients eligible for the open-label extension (OLE, weeks 52–204) received infliximab 3–6 mg/kg every 8 weeks plus methotrexate. Results Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively. Conclusions In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate. Clinical trials registration number NCT00036374.

To examine the change in health-related quality of life (HRQOL) and its determinants in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX).Patients were extracted from the PRINTO clinical trial which aimed to evaluate the efficacy and safety profile of MTX administered in standard, intermediate or higher doses (10, 15 and 30 mg/m(2)/week respectively). Children with polyarticular-course JIA, who were less than 18 years and had a complete HRQOL assessment were included.A total of 521 children were included. At baseline, patients with JIA showed poorer HRQOL (p0.01) than healthy children. In 207/412 (50%) and 63 (15%) children, HRQOL values were 2 standard deviations below the mean of healthy controls in the physical and psychosocial summary scale, respectively. After 6 months of treatment with standard dose MTX, there was a statistically significant improvement in all HRQOL health concepts, particularly the physical ones. Similar improvements were observed in those who did not respond to a standard dose of MTX and were subsequently randomised to a higher dose. The presence of marked disability at baseline was associated with a fivefold increased risk of retaining poor physical health after 6 months of active treatment with standard dose MTX. Other less important determinants of retaining poor physical well-being were the baseline level of systemic inflammation, pain intensity and an antinuclear-antibody-negative status.MTX treatment produces a significant improvement across a wide range of HRQOL components, particularly in the physical domains, in patients with JIA.

Objective: Juvenile idiopathic arthritis (JIA) is a chronic disorder in which both genetic and environmental factors are involved. Recently, we identified the TRAF1/C5 region (located on chromosome 9q33–34) as a risk factor for rheumatoid arthritis (RA) (p combined = 1.4×10 −8 ). In the present study the association of the TRAF1/C5 region with the susceptibility to JIA was investigated. Methods: A case–control association study was performed in 338 Caucasian patients with JIA and 511 healthy individuals. We genotyped the single nucleotide polymorphism rs10818488 as a marker for the TRAF1/C5 region. Results: The A allele was associated with the susceptibility to rheumatoid factor-negative polyarthritis with an 11% increase in allele frequency (OR 1.54, 95% CI 1.09 to 2.18; p = 0.012). This association was stronger when combining subtypes with a polyarticular phenotype (OR 1.46, 95% CI 1.12 to 1.90; p = 0.004). In addition, we observed a trend towards an increase in A allele frequency in patients with extended oligoarthritis versus persistent oligoarthritis (49%, 38% respectively); p = 0.055. Conclusions: Apart from being a well replicated risk factor for RA, TRAF1/C5 also appears to be a risk factor for the rheumatoid factor-negative polyarthritis subtype of JIA and, more generally, seems to be associated with subtypes of JIA characterised by a polyarticular course.

Background Childhood-onset panniculitides are rare and classically include infectious, connective tissue, malignant, metabolic, and drugs, cold or trauma-induced panniculitis. Some specific types of panniculitis are only seen in neonates and very young infants, and include subcutaneous fat of the newborn, poststeroid panniculitis, sclerema neonatorum, and cold panniculitis. However, no specific discoverable etiology can be identified in many patients. Objectives To describe the spectrum of clinical and pathological manifestations of childhood-onset panniculitis of unknown cause Methods A retrospective single-center study of children presenting with panniculitis diagnosed by skin biopsy Results Eighteen patients were identified. The onset of symptoms occurred within the first two years of life in 15/18 patients (83%). Panniculitis was the revealing manifestation in 15/18 (83%) patients, and relapsed in 13/18 (72%) patients. Associated-non-cutaneous features occurred in 16/18 (89%) patients, especially autoinflammatory manifestations in 13/18 patients (72%), associated with immunodeficiency in 5 patients (low T or B cells count with hypogammaglobulinemia in 4 and 1 patients respectively). Autoinflammatory manifestations consisted in attacks of fever with an elevation of acute phase reactants associated with polyarthritis or polyarthralgia (2 patients), rash (2 patients) or aseptic adenitis (2 patients). Panniculitis was mostly lobular in 10 (55%) patients, septal in 3 (17%) patients or both in 5 patients (28%). Predominant infiltrate consisted of neutrophils, cytophagic histiocytes, lymphocytes, eosinophils in 8 (44%), 5 (28%), 3 (17%), and 1 (5.5%) patients respectively, and included granuloma in 1 patient. No relationship was found between clinical and pathological features. Genomic mutations were identified in 3 of the 4 patients who underwent genetic analysis: mutations in TRNT1, MVK (mevalonate kinase) and LCK genes. Conclusions This series underlines that auto-inflammatory diseases, possibly associated with inherited immunodeficiency, are a main cause of early-onset panniculitis. The identification of a monogenic cause in 3 patients and the early-onset presentation of the disease suggest that a subset of patients has a genetic predisposition to develop panniculitis, especially early-onset panniculitis. Disclosure of Interest None declared

Background Systemic juvenile idiopathic arthritis (sJIA) is a disease characterized by arthritis and systemic features such as fever, rash, lymphadenopathy and leukocytosis. The underlying pathogenic mechanism of sJIA is not understood but prolonged stimulation of immune cells and excessive production of cytokines are considered to be important in the pathogenesis of the disease. Objectives The lack of a suitable animal model is a major drawback in the investigation of the pathogenesis of sJIA. We examined whether complete Freund’s adjuvant (CFA), a widely used reagent for chronic stimulation of the immune system, can elicit sJIA-like features in mice. Since interferon-gamma (IFN-γ) exerts key functions in activating and regulating innate and adaptive immune responses and given the disputable role of IFN-γ in sJIA patients, we examined our hypothesis in wild type as well as IFN-γ-deficient mice. Methods IFN-γ-deficient (IFN-γ KO) and wild type mice were injected s.c. with CFA. Body weight, clinical signs of arthritis, complete blood cell counts and peripheral blood biochemistry were monitored. Inflammatory cytokine levels were measured by qPCR and ELISA. Flow cytometry and histology were performed on spleen, liver, bone marrow and lymph nodes. Results Consistent with the immune stimulating properties of CFA, both IFN-γ KO and wild type mice showed splenomegaly and lymphadenopathy from 10 days after CFA challenge onward. Both substrains also developed weight loss; however, while this was transient in wild type animals, it was prolonged and more severe in IFN-γ KO mice. Furthermore, a proportion of the IFN-γ KO, but not wild type mice developed skin rashes as well as redness and swelling in the joints, histologically consistent with prominent synovitis. Complete blood counts demonstrated an increase in platelets and neutrophils in both substrains of mice, the increase being more pronounced in IFN-γ KO mice. IL-6 serum levels were significantly elevated in CFA-challenged IFN-γ KO mice only. Interestingly, between 11 to 40 days post CFA injection, approximately 30% of IFN-γ KO mice developed cytopenia and anemia, as evident from their significantly decreased lymphocyte and red blood cell counts, and decreases in hemoglobin and hematocrit levels. Intriguingly, in CFA-challenged IFN-γ KO mice, bone marrow, spleen, liver and blood showed a prominent infiltration of macrophages, including increased numbers of hemophagocytic macrophages. Conclusions Upon challenge with CFA, IFN-γ KO mice developed clinical, biological and pathological features similar to those seen in patients with sJIA. A proportion of these mice also developed severe inflammation with wasting, anemia and hemophagocytosis, features that are seen in a subset of sJIA patients, diagnosed with macrophage activation syndrome (MAS). To our knowledge, this is the first animal model of sJIA showing an association with MAS. Our data demonstrate that IFN-γ is not required for chronic anemia and hemophagocytosis and challenge the concept that IFN-γ is the critical driver of MAS. Disclosure of Interest None Declared

Background Dry synovitis (DS) is considered to be a rare form of juvenile idiopathic arthritis (JIA), incompletely understood and following a potentially destructive course. Since its first description only a few reports mention this entity within the spectrum of JIA. Objectives To describe the clinical and radiological manifestations and clinical course of DS and to compare it with classic polyarticular RF negative JIA (c-poly JIA). Methods We performed a retrospective study of 10 patients followed in 3 pediatric rheumatology centers who presented with progressive articular limitations without clinical synovitis and radiologic signs of articular damage. This cohort was compared with a cohort of 35 consecutive patients with classical polyarticular RF negative JIA, seen at the Pediatric Rheumatology Unit of Padua in the period January-June 2012. Clinical, laboratory and imaging (X-rays, MRI) data of both groups were reviewed and compared. Treatment was grouped in 4 categories: no treatment, just corticosteroids (CS), Methotrexate (MTX) + CS, Biological agents (BA) + MTX. Outcome measures included growth, remission state as: clinical remission without medication (CR), clinical remission on medication (CRM), progressive arthropathy with mild functional disability (PA), severe arthropathy with ankylosis and irreversible disability (SA). Results The cohort included 4 male and 6 female, mean (range) age at first manifestation and diagnosis were respectively 4.3 yrs (1.3-8.5) and 7.3 yr (2.8-14). Presenting signs included delayed motor development, progressive articular stiffness and contractures. Little or no pain was present. Clinical examination showed a symmetric and polyarticular involvement without clinical signs of synovitis. CRP was normal in all and ESR>20mm/h in 1/10. In 9/10 patients ANA were absent. Radiological imaging showed osteopenia and/or erosions in all patients. MRI revealed synovial thickening in 9/10 patients; bone edema was variably present and bone erosions were demonstrated in 8/10 patients. Treatments comprised NSAIDs (n=8/10), corticosteroids (n=8/10), methotrexate (n=9/10), biological agents (anti-TNF, IL-RA) (n=6/10). The comparison of DS with c-poly JIA showed that the age at disease onset and at diagnosis were comparable in the two groups. Significant differential features of DS resulted: higher diagnostic delay, increased number of joint involved and joint contractures, lack of swelling/tenderness, prevalent upper limbs involvement, lack of acute phase reactants (ESR, CRP) and no ANA detection. X-ray revealed a significant higher prevalence of osteopenia, erosions and bone edema at MRI in DS. At the last evaluation 77% of patients with c-poly JIA were in CR or CRM while 50% of DS had PA. Growth was significantly impaired in DS (p 0.016). Conclusions Dry Synovitis is actually considered as a subtype of polyarticular JIA. Our study clearly shows that it represents a distinct and unique entity characterized by increased number of joint involved and contractures, prevalent upper limbs involvement, progressive course and lack of acute phase reactants or autoantibodies elevation. The exact nature of DS entity and the possible contribution of metabolic or intrinsic bone disorders into its pathogenesis remain to be determined. Disclosure of Interest None Declared

Background The main limitation to a better knowledge of Autoinflammatory diseases is related to the extreme fragmentation of the diagnosed cases that are spread over different centers and countries. The general aim of the Eurofever Project (agreement n 2007332, EAHC) is to build an international registry on Autoinflammatory diseases. Objectives To evaluate the number of patients enrolled in the Registry in the first 24 months after starting the enrolment. Methods A web-based registry collecting baseline and clinical information on Autoinflammatory diseases is available in the member area of the PRINTO web-site. The following monogenic autoinflammatory diseases were considered: FMF, CAPS, TRAPS, mevalonate kinase deficiency (MKD), Blau’s syndrome, PAPA, DIRA, NLRP12-mediated periodic fever. Information on CRMO, Behcet’s disease, PFAPA and undefined periodic fevers were also collected. Results During the first 24 months from the beginning of the enrolment 2293 patients from 51 centers in 38 countries have been entered in the registry. At present baseline demographic information from 2293 (M:F=1121:1172) patients are available. In 1797 (78%) complete information on clinical manifestations form disease onset to diagnosis and response to treatment is also available. For each disease the number of enrolled patients is: FMF 694 pts (493 with complete clinical data); TRAPS 215 pts (180 with with complete clinical data); CAPS 180 pts (155 with complete clinical data); MKD 129 pts (107 with complete clinical data); Blau’s disease 30 pts (18 with complete clinical data); PAPA 8 pts (all with complete clinical data); NLRP-12 mediated periodic fever 6 pts – 4 with complete clinical data); DIRA 3 pts (all with complete clinical data). In total 19 new mutations have been reported in 22 pts. Among multifactorial autoinflammatory diseases: PFAPA 405 pts (264 with complete clinical data); CRMO 372 pts (334 with complete clinical data); pediatric Bechet disease 79 pts (64 with complete clinical data) and 173 patients with undefined periodic fever (167 with complete clinical data). Conclusions A common registry for collection of patients with Autoinflammatory disease is available and the enrolment is ongoing. The analysis of data on the clinical presentation, outcome and response to treatment of Autoinflammatory diseases and comparative studies among different Autoinflammatory conditions are ongoing. Disclosure of Interest None Declared

Background The autoinflammatory syndromes (AISs) include monogenic and polygenic disorders characterized by primary dysfunction of the innate immune system. Objectives To describe the clinical spectrum, genetic background and therapy in a cohort of AIS patients followed in a reference Pediatric Rheumatology center. Methods Medical records of AIS patients followed until November 2010 and entered in the Eurofever Registry were studied. Results Fifty six patients were included: 17 CAPS, 4 TRAPS, 5 HIDS, 18 FMF, 6 CRMO, 2 SAPHO and 4 Behcet’s Disease (BD). The median follow-up was 2 years (0-14 years). The male/female ratio was 20/36. The median age was 2.5 years at disease onset and 4 years at diagnosis. Family history was positive in 34% of patients. Clinical manifestations included fever (79%), musculoskeletal (77%), gastrointestinal (63%), mucocutaneous (61%), neurological (41%), ocular (34%), cardiorespiratory (13%), and genitourinary (2%) findings, lymphadenopathy with/or hepatosplenomegaly (16%) and growth impairment (25%). The main organ system manifestations were arthralgia (70%), abdominal pain (50%), urticarial rash (34%), headache (34%), conjunctivitis (16%), generalized lymph node enlargement (13%), and chest pain (9%). Complications/sequelae developed in 45% of patients and involved the musculoskeletal (25%), neurological (21%), gastrointestinal (11%) and ocular (7%) systems. Six patients presented with severe/unusual manifestations: neonatal peritonitis (1 CAPS), pancreatitis (1 TRAPS), acute glomerulonephritis (1 FMF), complicated Henoch-Schonlein purpura (1 FMF), peritoneal adhesions with intestinal occlusion (1 FMF), periorbital pain (1 CRMO) and cerebral thrombosis (1 BD). AISs were associated with other diseases in 2 patients (FMF/Henoch-Schonlein purpura and CRMO/enthesitis-related arthritis). One mutant allele was found in 16/17 CAPS, 4/4 TRAPS and 4/18 FMF patients. Two mutant allelles were present in 5/5 HIDS and 11/18 FMF patients.The most used therapeutic agents were biologics (54%) (anakinra, canakinumab, etanercept, adalimumab), NSAIDs (48%), colchicine (45%) and corticosteroids (29%). Anti-interleukin-1 therapy and colchicine proved efficacy in CAPS and FMF patients, respectively. In addition, favorable responses demonstrated anti-interleukin-1 therapy in TRAPS, HIDS and colchicine-resistant FMF patients, as well as etanercept in TRAPS, HIDS and CRMO patients non-responsive to NSAIDs. Fifty seven% and 41% of patients were in complete and partial remission, respectively, at last visit. Conclusions AISs in children are associated with a broad spectrum of manifestations. A detailed history, thorough review of clinical manifestations and molecular testing of specific causative genes can provide early and accurate diagnosis and institution of efficient therapy. Disclosure of Interest None Declared

Background Systemic juvenile idiopathic arthritis (sJIA) is one of the most severe pediatric systemic immune-inflammatory disorders, characterized by arthritis and systemic features including fever, rash, lymphadenopathy and leukocytosis. A frequent, potentially fatal complication of sJIA is macrophage activation syndrome (MAS). An excessive production of pro-inflammatory cytokines has been demonstrated in sJIA with or without MAS, yet the exact cause and pathogenesis are still unknown. Studies on gene expression profiles performed on freshly isolated peripheral blood mononuclear cells (PBMCs) from sJIA patients revealed a conspicuous absence of interferon-gamma (IFN-γ)-upregulated genes. This is a peculiar finding, given the highly inflammatory nature of sJIA and the concept that IFN-γ is a driver of MAS. Objectives In this study we explored whether PBMCs of sJIA patients have a defect in IFN-γ signaling by studying induced genes and proteins upon in vitro stimulation with IFN-γ. Methods 9 sJIA patients (7 under treatment and in remission, 1 with active disease despite treatment, 1 untreated) and 1 sJIA patient presenting with MAS were recruited from the University Hospital of Leuven after giving informed consent. PBMCs from patients and healthy controls were obtained by gradient centrifugation and were cultured for 24 hours in the presence or absence of IFN-γ. RNA was extracted from the harvested cells. cDNA was synthesized and qPCR was performed on different IFN-γ-induced genes. IFN-γ-induced proteins (interferon-induced protein (IP-10) and monocyte chemotactic factor-1 (MCP-1)) were analyzed in supernatant of cells, by ELISA. Results In PBMCs from healthy control patients, IFN-γ induced - as expected - upregulation of STAT 1 mRNA, an important IFN-γ-induced transcription factor, as well as other IFN-γ-induced genes such as indoleamine 2,3-dioxygenase (IDO) and IP-10. Some genes such as suppressor of cytokine signaling 3 (SOCS3), MCP-1 and interferon regulatory factor-1 (IRF-1) were not upregulated in healthy PBMCs. Most importantly, all of the IFN γ-associated genes that were significantly induced in healthy control PBMCs were at the least equally well induced in sJIA patients (in both treated, untreated and MAS conditions). Significant production of IP-10 protein was found in the supernatant of IFN-γ-stimulated PBMCs, and here again there was no difference between patients and controls. Conclusions We conclude that PBMCs from sJIA/MAS patients have no intrinsic defect in the IFN-γ machinery. Thus the absence of an IFN-γ signature in sJIA, as reported in gene expression studies, cannot be explained by decreased in vitro responsiveness of PBMCs to IFN-γ, and further research is required to explain this discrepancy. Disclosure of Interest None Declared

Background Magnetic Resonance Imaging (MRI) is a very sensitive method to demonstrate muscle inflammation, but there is no standardized scoring system to assess both inflammation and damage in juvenile dermatomyositis Objectives To propose and to validate a MRI scoring system assessing acute inflammation and damages findings in Juvenile Dermatomyositis (JD). Methods Children with JD referred to our institution for proximal thighs MRI between 1998 and 2009 were retrospectively included. The MRIs were analysed twice by two musculoskeletal paediatric radiologists with a 6 weeks interval. Inflammatory activity was scored including muscle œdema (0=none, 1=mild and 2=severe), fascial, subcutaneous fat and skin œdema (qualitative scale). Damages were scored including calcinosis in muscles, fascias, subcutaneous fat and skin (qualitative scale), muscle and fat atrophy (qualitative scale) and muscle fatty infiltration (0=none, 1=mild and 2=severe). Results 20 children were included (median age, 7.1 years; range, 1-15; 6 boys and 14 girls). 45 MRI were analysed, which 10 were performed in the 2 months diagnosis. The most common MRI findings were muscle œdema (80%) regarding inflammatory activity, and muscle fatty infiltration (24%) regarding damages. Both intra- and inter-observers agreements were excellent regarding global score (Intraclass Correlation Coefficient [ICC], from 0.95 [CI 95%, 0.87-0.98] to 0.97 [0.94-0.99] and 0.88 [0.74-0.95], respectively). Inter-observer ICC were also excellent regarding inflammatory and damage subscores (0.84 [0.73-0.91] and 0.89 [0.66-0.97], respectively). Conclusions MRI is a reliable and reproductible tool for analysing inflammatory activity and damage during JD. Disclosure of Interest None Declared

Background Systemic juvenile idiopathic arthritis (SJIA) is an IL1β-mediated autoinflammatory disease, characterized by spiking intermittent fever, rash, and arthritis. Canakinumab (CAN), a selective, fully human, anti-IL1β monoclonal antibody has shown promising efficacy and safety data in SJIA patients (pts). Objectives To demonstrate CAN allows tapering of corticosteroids (CS) and to evaluate time to flare in CAN vs placebo (PCB) pts with SJIA and active systemic features. Methods This Phase 3 trial had two parts. In Part 1 (P1), all patients (2-20 yrs) received open label CAN to identify responders and to taper CS. In Part 2 (P2), pts who successfully tapered their CS were randomized to receive CAN or PCB. In P1, pts received CAN (4mg/kg; max 300 mg) sc injection every 4 wks. Primary objectives were to determine if ≥25% of pts on CS at study entry could successfully taper the CS dose (P1); if time to flare was longer for CAN vs PCB (P2), and safety. Results 177 pts (128 on CS; 49 steroid-free) entered P1, of which 100 pts (CAN, n=50; PCB, n=50) entered P2; most of the remaining 77 pts were eligible (>ACR30 at Day 15) to directly enter an open-label extension study following P1. In P1, 92 pts attempted CS tapering and 57 (62%) were successful, representing 44.5% (57/128; p Conclusions For SJIA patients with active features, canakinumab sc injection every 4 weeks allowed successful steroid tapering, with one third being able to discontinue their CS. Canakinumab significantly decreased the risk of SJIA flare, while demonstrating an acceptable safety and tolerability profile. Disclosure of Interest N. Ruperto Grant/Research support from: Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini” s.p.a, Glaxo Smith & Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, Novartis, Bristol Myers and Squibb, Roche, Janssen Bilogics B.V., H. Brunner Consultant for: Novartis, UCB, Genentech, Jansen, GSK and Medimmune, Paid Instructor for: Participant in Scientific Advisory Committee for Canakinumab program in SJIA, P. Quartier Speakers Bureau: Novartis, T. Constantin: None Declared, N. Wulffraat: None Declared, G. Horneff Grant/Research support from: Abbott, Pfizer, Consultant for: Abbott, Pfizer, Novartis, Roche, R. Brik: None Declared, L. McCann: None Declared, O. Kasapcopur: None Declared, L. Rutkowska-Sak: None Declared, R. Schneider Consultant for: Hoffman-La-Roche, Speakers Bureau: Hoffman-La-Roche, Y. Berkun: None Declared, I. Calvo: None Declared, M. Erguven Grant/Research support from: Novartis, L. Goffin: None Declared, M. Hofer Consultant for: Novartis, T. Kallinich Speakers Bureau: Novartis, S. Knupp: None Declared, Y. Uziel Consultant for: Novartis, S. Viola: None Declared, K. Nistala Grant/Research support from: Arthritis Research UK Career Progression Fellow, C. Wouters: None Declared, R. Cimaz: None Declared, M. Ferrandiz Grant/Research support from: Novartis, B. Flato: None Declared, M. Luz Gamir: None Declared, I. Kone-Paut: None Declared, A. Grom Consultant for: Novartis, J&J, B. Magnusson Grant/Research support from: Swedish Association of local Authorities and Regions, Consultant for: Roche AB, S. Ozen Consultant for: Novartis, F. Sztajnbok: None Declared, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, D. Kim Shareholder of: Novartis, Employee of: Novartis, K. Abrams Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/Research support from: Abbott, Astrazeneca, Bristol Myers and Squibb, Centocor Research & Development, Eli Lilly and Company, “Francesco Angelini” s.p.a, Glaxo Smith & Kline, Italfarmaco, Merck Serono, Novartis, Pfizer Inc., Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, Novartis, Bristol Myers and Squibb, Glaxo Smith & Kline, D. Lovell Consultant for: Abbott Laboratories, Centocor Inc, Amgen, Astra Zeneca Pharmaceutical, Bristol-Myers Squibb, Hoffmann-La Roche, Inc., Novartis Pharmaceutical Corporation, Pfizer Inc, Regeneron, UBC, Wyeth Pharmaceuticals, Xoma Corporation, Speakers Bureau: Wyeth Pharmaceuticals