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Objective To develop and validate new Juvenile Arthritis Disease Activity Score 10 (JADAS10) and clinical JADAS10 (cJADAS10) cutoffs to separate the states of inactive disease (ID), minimal disease activity (MiDA), moderate disease activity (MoDA), and high disease activity (HDA) in children with oligoarthritis and with rheumatoid factor-negative polyarthritis, based on subjective disease assessment by the treating pediatric rheumatologist. Methods The cutoffs definition cohort was composed of 1,936 patients included in the multinational Epidemiology, Treatment and Outcome of Childhood Arthritis (EPOCA) study. Using the subjective physician rating as an external criterion, 4 methods were applied to identify the cutoffs: mapping, Youden index, 90% specificity, and maximum agreement. The validation cohort included 4,014 EPOCA patients, patients from 2 randomized trials, and 88 patients from the PharmaChild registry. Cutoff validation was conducted by assessing discriminative and predictive ability. Results The JADAS10 cutoffs were 1.4, 4, and 13, respectively, for oligoarthritis and 2.7, 6, and 17, respectively, for polyarthritis. The cJADAS10 cutoffs were 1.1, 4, and 12, respectively, for oligoarthritis and 2.5, 5, and 16, respectively, for polyarthritis. The cutoffs discriminated strongly among different levels of pain and morning stiffness, between patients who were and those who were not prescribed a new medication, and between different levels of improvement in clinical trials. Achievement of ID and MiDA according to the new JADAS cutoffs at least twice in the first year of disease predicted better outcome at 2 years. Conclusion The 2021 JADAS and cJADAS cutoffs revealed good metrologic properties in both definition and validation samples, and are therefore suitable for use in clinical trials and routine practice.

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

Contains fulltext : 231528.pdf (Publisher’s version ) (Closed access) BACKGROUND: TNF receptor-associated periodic syndrome (TRAPS) is a rare autoinflammatory disease caused by dominant mutation of the TNF super family receptor 1A (TNFRSF1A) gene. Data regarding long-term treatment outcomes are lacking. OBJECTIVE: To assess correlations of genotype-phenotypes in patients with TRAPS, as defined by the International Study Group for Systemic Autoinflammatory Diseases (INSAID) classification and Eurofever criteria, with treatment responses. METHODS: Data from 226 patients with variants of the TNFRSF1A gene and enrolled in the Eurofever registry were classified according to the INSAID classification in groups A (pathogenic or likely pathogenic variants), B (variants of uncertain significance or not classified variants), and C (benign or likely benign variants) and screened for Eurofever criteria. RESULTS: In group A (127 of 226 patients, 56%), all fulfilled Eurofever criteria and 20 of 127 patients (16%) developed AA amyloidosis. In group B (78 of 226 patients, 35%), 40 of 78 patients (51%) did not fulfill Eurofever criteria, displaying a lower incidence of abdominal pain (P < .02) and higher efficacy rate of on-demand nonsteroidal anti-inflammatory drugs (P 85% complete response). No patients on anti-IL-1 treatments developed AA amyloidosis, and 7 women with a history of failure to conceive had successful pregnancies. CONCLUSION: Anti-IL-1 drugs are the best maintenance treatment in patients with TRAPS. The diagnosis of TRAPS should be considered very carefully in patients of group B not fulfilling Eurofever criteria and group C, and colchicine may be preferable as the first maintenance treatment.

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 Russian language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 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). A total of 100 JIA patients (25% systemic, 19% oligoarticular, 38% RF-negative polyarthritis, 18% other categories) and 198 healthy children, were enrolled in two centres. The JAMAR components discriminated healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Russian 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 clinical research.

ObjectivesTo describe the clinical characteristics, treatment response and genetic findings in a large cohort of patients with undefined systemic autoinflammatory diseases (SAIDs).MethodsClinical and genetic data from patients with undefined SAIDs were extracted from the Eurofever registry, an international web-based registry that retrospectively collects clinical information on patients with autoinflammatory diseases.ResultsThis study included 187 patients. Seven patients had a chronic disease course, 180 patients had a recurrent disease course. The median age at disease onset was 4.3 years. Patients had a median of 12 episodes per year, with a median duration of 4 days. Most commonly reported symptoms were arthralgia (n=113), myalgia (n=86), abdominal pain (n=89), fatigue (n=111), malaise (n=104) and mucocutaneous manifestations (n=128). In 24 patients, relatives were affected as well. In 15 patients, genetic variants were found in autoinflammatory genes. Patients with genetic variants more often had affected relatives compared with patients without genetic variants (p=0.005). Most patients responded well to non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, colchicine and anakinra. Complete remission was rarely achieved with NSAIDs alone. Notable patterns were found in patients with distinctive symptoms. Patients with pericarditis (n=11) were older at disease onset (33.8 years) and had fewer episodes per year (3.0/year) compared with other patients. Patients with an intellectual impairment (n=8) were younger at disease onset (2.2 years) and often had relatives affected (28.6%).ConclusionThis study describes the clinical characteristics of a large cohort of patients with undefined SAIDs. Among these, patients with pericarditis and intellectual impairment appear to comprise distinct subsets.

Background:Juvenile dermatomyositis (JDM) is the most common idiopathic inflammatory myopathy (IIM) of childhood, but the involvement of muscle also can be complication of systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) and different overlap syndromes. The presence of myopathy can significantly affect the prognosis of the disease and the quality of life. Despite of the absence of official indication for biological therapy fo IIM, it`s may be needed in severe course of disease.Objectives:To analyze in retrospective study the efficacy and safety of Biologics (B) in patients (pts) with IIM in our pediatric rheumatology center.Methods:The study included all pts with rheumatic diseases (RD), who had IIM and received B during past 10 years.Results:A total of 17 pts (10 females) were identified: 23.5% with JDM, 11.8% - SLE, 35.3% - MCTD, 29.4% - overlap syndromes. The median age at the onset of RD was 9.75 years [interquartile range (IQR) 6.9; 13.5]. The median disease duration at the onset of myopathy was 7.0 months [3.0; 10.0], in all pts with JDM – at onset. All pts had myopathic syndrome. The rash tipical for JDM was in 8 pts (47%). The lung involvement observed in 6 pts (35.3%). Levels of serum muscle enzymes (CK, ALT, AST and lactate dehydrogenase [LDH]) were elevated in 88.2% of pts: CK in 52.9% (mean ± std 624.35±1007.2 U/L), ALT – 82.4% (mean ± std 142.18±148.16U/L), AST – 82.4% (mean ± std 159.6±201.1 U/L), LDH – 88.2% (mean ± std 492.5±229.2 U/L). Abnormal EMG findings were in 10 pts (59.4%). Nailfold capillaroscopic changes tipical for IIM had 10 pts (59.4%). Before B 94.1% of pts received corticosteroids (CS), 58.8% - methotrexate, 29.4% - hydroxychloroquine, 17.6% - cyclophosphamide, 11.8% - cyclosporine, 5.9% - mycophenolate mofetil, 5.9% - azathioprine, 47% - IVIG. B therapy was started due to insufficient efficacy of previous therapy. The median age at start of B was 12.3 years [IQR 9.5; 15.0]. The median disease duration prior to treatment with B was 2.25 years [IQR 0,8; 3.6]. 58.8% of pts received rituximab (RTX), 41.2% - abatacept (ABA). The median time between each course of RTX was 182 days [IQR 156–315]. 80% of pts underwent more than one course of RTM therapy, with a maximum of 5 courses. The median duration of ABA therapy was 2.8 years [IQR 1.6; 5.0]. Discontinuation of B due to serious AE was observed in 1 patient with overlap syndrome (5.9%) – macrophage activation syndrome (MAS) 8 day after RTX infusion (5th course, 1st infusion). One patient (female, 12.3 yo) died from MAS (at onset of SLE, developed before B), the others achieved remission. B therapy allowed to reduce the dose of CS to maintenance in all pts, decrease of calcinosis in 2 pts and improve the quality of life.Conclusion:Our study demonstrated that B is highly effective in children with IIM and have the acceptable safety. Early diagnosis and initiation of intensive therapy are important in reducing symptoms of myopathy in RD. It seems that the development of IIM in other RDs, not JDM, indicates the need for B and its good efficacy. The further extended studies are needed.Disclosure of Interests:None declared

Background:About one year ago at the beginning of the new SARS-CoV-2 infection pandemic, it was expected, that rheumatic disease (RD) and immunosuppressive therapy could predispose to a more severe course of the Covid-19 infection. At that time, it was unspeakable how this infection would occur in children with RВ in compare to adults. Now it’s time to draw preliminary conclusions.Objectives:to analyze all features of COVID19 infection in children with RDMethods:The retrospective single center study of all patients with pediatric RD who had the COVID19 infection up to the end of January 2021. It was analyzed all variety of clinical manifestations, changing in therapy at the time of COVID-19 and after it, the dynamics of the RD and consequences of the new viral disease.Results:The study included 66 patients under the age of 18 with various RS, including autoinflammatory disease (AIDs). The diagnostic distribution, sex ratio, age and previous therapy present in the Table 1. There were patients treated with DMARDS (methotrexate -47, hydroxychloroquine -3, mycophenolate mofetil -2, colchicine -1), NSAID monotherapy -6, systemic steroids -10; 29 patients recived Biologics, including combination with methotrexate. None of our patients had a severe course of the COVID-19, none of 66 patients was hospitalized for emergency indications in the intensive care unit or in other specialized departments. The diagnosis of Covid-19 infection was based on different evidences: positive PCR in 15 (23%) cases, high levels of immunoglobulins G and M - in 64 (97%) and 7 (11%) respectively, viral pneumonia was confirmed by CT in 2 (10%) cases. A manifest clinical picture presented just in 21 (32 %) of patients, the others were carried the disease asymptomatically. Among the clinical manifestations of SARS-CoV-2 that were observed in our patients were the following: fever, as the most frequent symptom - 19 (90%), rhinitis - 12 (57%), anosmia - 10 (48%), sore throat - 3 (14%), arthralgia/myalgia in 4 (19%), rash - 1 (5%) case, cough - 4 (19%) cases. it is important to note that until July 2020, only 4 patients were registered, and in the next 6 months – 62. The treatment against Covid-19 in our patients with clinical symptoms included: NSAID monotherapy -4 (19%), Systemic steroids -2 (10%), Hydroxychloroquine -2(10%), Antibiotics-5 (24%).Table 1.Clinical characteristics of children with RD according to presence of symptoms of Covid-19ParameterCovid-19 symptomatic course (n=21)Covid-19 asymptomatic course (n=45)p-valuesSex ratio (F/M)9/1230/15nsDuration of RD (Me. Years)4 (2;6)4 (2;7)nsAge(years)Me>10 yrs15 (13; 17)12011 (8;13.5)1926Covid-19 evidencesIgG Covid-19 +1945nsIgM Covid-19 +34nsPCR Covid-19 +110nsDiagnosis of RDJIA non-systemic1431nssJIA13nsSLE41nsJDM11nsScleroderma6nsAIDs (CAPS, FMF, FOP)13nsPrevious therapyNSAID monotherapy36nsDMARDs1633nsSystemic steroids47nsTNF-inhibitors512nsAbatacept13nsIL6-inhibitors (Tocilizumab, Sarilumab)02nsJAK-kinase inhibitors12nsWorsening/flare of RD after Covid-19 infection50pConclusion:Our study suggests that the presence of RD and immunosuppression therapy does not lead to an increased frequency or severe course of Covid-19 infection in children. The final conclusion will be drawn as the data accumulates.Disclosure of Interests:None declared

Background:Biological agents (BA), especially TNF inhibitors, are high efficacy options for current therapy for patients (pts) with juvenile idiopathic arthritis (JIA). They are successfully used not only for the arthritis but also for JIA-associated uveitis, however, development of uveitis de novo in pts treated with BA is a well-established paradoxical phenomenon.Objectives:to evaluate the frequency of new onset (no-) uveitis, occurring under BA therapy in JIA pts, to establish clinical features, which may be associated with development of such effects.Methods:retrospective cohort study involved all JIA pts (1136) who were treated with BA in our clinic from 2004 to 2020. All cases of no-uveitis were collected for the describing of their clinical features in disease onset and course, activity level, JIA category, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27.Results:among of 1136 pts treated with different BA we identified 36 (3.3%) pts (19 female/17 male) with no-uveitis under BA. Mostly during etanercept (ETA) therapy (34 cases from 488 ETA courses, 7%), 1/166 - in abatacept (ABA) and 1/372 - in adalimumab (ADA). 30 pts (83%) with no-uveitis developed it on the 1st line of BA treatment (29 ETA vs 1 ADA). 4pts (11%) developed no-uveitis on 2 nd line (3 ETA vs 1 ABA). 2 pts (6%) on third line (all ETA, both pts had also psoriasis). There are no cases of no-uveitis under other BA. Frequency of no-uveitis was much higher in ETA group. ETA exposure was 26.8 ± 28.8 months (mo). It means there are no “safe” period of therapy from paradoxical phenomenon of no-uveitis. JIA subtypes were as follows: RF-neg polyarthritis 9 (25%), persistent oligoarthritis 3 (8%), extended oligoarthritis 21 (59%), enthesitis-related arthritis (ERA) - 3 (8%). Average age at JIA onset was 4.6 ± 3.9 yrs. 20/36 patients had high laboratory activity (CRP 54 ± 23 mg/l; ESR 41 ± 19 mm/h) and severe arthritis before BA initiation. However most of pts (25/36) achieved 90-100% ACRpedi-response by the uveitis development. 23/36 pts were ANA-positive, 17/36 pts had HLAB27, including 7 pts who had the both features. Uveitis was occurred earlier in ANA plus HLAB27 positive pts (mean exposure - 15.3 mo) than in only ANA-positive or HLAB27-positive pts (27.7 mo and 27.6 mo accordingly). 29/36 (81%) of pts received methotrexate (MTX) in mean dosage 11.5 mg/m2/week. There are no differences in time of uveitis development depending of MTX. In all cases of no-uveitis BA was switched.Conclusion:Our study suggested that new onset of uveitis is rare adverse event during BA therapy in JIA. Uveitis can develop despite the excellent effect of therapy on joint manifestation. The most typical development of no-uveitis is under ETA therapy, especially in the predisposed cases (certain variants of JIA, ANF positivity, HLAB27 presence) and in patients with very high disease activity at the time of the start of biological therapy.Disclosure of Interests:Irina Nikishina Speakers bureau: Novartis, MSD, Pfizer, Abbvie, Hofman la Roche, Svetlana Arsenyeva: None declared, Maria Kaleda Speakers bureau: Novartis, Roche, MSD, Olga Kostareva: None declared, Anna Shapovalenko: None declared, Ekaterina Denisova: None declared, Anna Panova: None declared

Background:Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is one of the best-known monogenic auto-inflammatory disorders resulting from an autosomal dominant variation in the TNF super family receptor 1A (TNFRSF1A) gene (1).Objectives:To define best treatment approach in patients with TRAPS and effect on long-term outcomes.Methods:We reviewed all data on patients with TRAPS enrolled in the Eurofever international registry according the INSAID gene variant classification and the new Eurofever/PRINTO classification criteria (EPCC).Results:Data on 226 patients were available. Patients not fulfilling the EPCC carrying likely benign/benign variants (21 patients, 9%) or VOUS/not classified variants (40 patients, 18%) displayed a milder disease than the patients fulfilling the EPCC with VOUS/not classified variants (38 patients, 17%) or pathogenic/likely pathogenic variants (127 patients, 56%). In particular, in patients not fulfilling the EPCC, less frequent abdominal pain and skin rashes, higher efficacy rate of colchicine and no development of AA amyloidosis have been reported. Almost 90% of patients fulfilling the EPCC required maintenance therapy and anti-interleukin (IL)-1 drugs were the most frequently used, with the highest efficacy rate (>85% complete response), while Etanercept was less effectively used and discontinued in 65% of patients.Conclusion:Anti-IL-1 drugs are the best maintenance treatment in TRAPS with potential to reverse the most serious disease complications of AA amyloidosis and infertility. The diagnosis of TRAPS should be considered very carefully in patients carrying VOUS/not classified variants not fulfilling the EPCC.References:[1]Lachmann HJ, Papa R, Gerhold K, Obici L, Touitou I, Cantarini L, et al. The phenotype of TNF receptor-associated autoinflammatory syndrome (TRAPS) at presentation: a series of 158 cases from the Eurofever/EUROTRAPS international registry. Annals of the rheumatic diseases 2014;73:2160-7.Acknowledgments:RP would like to thank the European Federation of Immunology (EFIS) for the short-term bursary and HL for her continuous support and guidance during the fellowship at the National Amyloidosis Centre in London.Disclosure of Interests:Riccardo Papa: None declared, Thirusha Lane: None declared, Francesca Bovis: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Isabelle Touitou: None declared, Luca Cantarini: None declared, Marco Cattalini: None declared, Laura Obici: None declared, Annette Jansson: None declared, Alexander Belot: None declared, Beata Woska-Kuśnierz: None declared, Rainer Berendes: None declared, Agustin Remesal: None declared, Marija Jelusic: None declared, Graciela Espada: None declared, Irina Nikishina: None declared, Esther Hoppenreijs: None declared, Maria Cristina Maggio: None declared, Taryn Youngstein: None declared, Tamer Rezk: None declared, Charalampia Papadopoulou: None declared, Paul Brogan Grant/research support from: Roche, Novartis, SOBI, Chemocentryx, Novimmune, Consultant of: Roche, SOBI, UCB, Novartis, Speakers bureau: Roche, SOBI, UCB, Novartis, Philip N Hawkins: None declared, Patricia Woo: 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, Marco Gattorno Consultant of: Sobi, Novartis, Speakers bureau: Sobi, Novartis, Helen J. Lachmann: None declared

Background:Juvenile psoriatic arthritis (JPsA) is one of the clinical variants of juvenile idiopathic arthritis (JIA), which is often characterized by an unfavorable course, refractory to therapy, requiring the prescription of Biological agents (BA).Objectives:analysis of BA use in patients with JPsA and therapy survival, switching to another line of BA.Methods:the retrospective cohort study included 1095 JIA patients who received BA and were observed in our clinic from 2004 to 2019. All cases of new onset psoriasis were collected; clinical features of disease onset and course, exposure to Methotrexate (MTX) and BA, presence of ANA, HLA B27 were studied.Results:among 1095 JIA patients who received BA over the past 15 years, a separate cohort of patients with JPsA for analysis was allocated. We identified 50 pts (57% female) aged 2-18 years (Me 13.3) at the time of initiation of therapy. All patients met the JPsA classification criteria, the average age of arthritis onset was 7.4±5.3 years (ME 6.75). However, cutaneous psoriasis occurred only in 68 %(34 pts), with manifestation at the age of 10±5 years. In 25 of 34 pts (73.5%) the development of psoriasis was preceded by joint manifestations in an average of 5±3.9 (ME 3) years. 6 pts from 1095 (0.65%) developed psoriasis under BA therapy: infliximab - 2 cases (0.62/100PY), adalimumab - 3 (0.15/100PY), abatacept -1 (0.31/100PY). 2/6 pts was ANA+, 3/6 – HLA B27+. Average age of disease onset was 9.8±7.8 years; BA exposure before psoriasis was 2.7±1.1 years and in 3.6±1.3 (ME 4) after the onset of arthritis. Therapy was continued in 4/6 pts; switched from infliximab to adalimumab in 2. Serious comorbid pathology was associated with JPsA in 7 pts (type 1 diabetes mellitus – 2 pts; Down syndrome; endogenous mental illness (schizophrenia); oligophrenia; ovaries polycystic; acute lymphoblastic leukemia in a state of incomplete remission). The clinical picture of the disease was represented by polyarthritis in 84%, oligoarthritis in 8%, the same number of patients 8% had an axial lesion. Sacroiliitis was detected in 20 patients (40%), dactylitis in 21 (42%), and uveitis in 10 (20%). HLA B27 was detected in 16/35 pts (45%), 32% pts were ANA-positive. The duration of the disease at the time of application of the first BA was 5±4 (Me 3.75) years. In 49 patients, BA was used in combination with methotrexate. The total number of BA courses switching included was 80 (infliximab-19, adalimumab-22, etanercept-27, golimumab-4, abatacept-5, tocilizumab-2, rituximab-1). 49% of patients have experience of using >2 BA (16 pts-2 BA, 4 pts-3 BA, 1 pt - 5 BA). Primary/secondary inefficiency (18/35; 51%), adverse events (8/35; 23%), organizational difficulties in market access mostly after the age of 18 (7/35; 20%), and remission (2/35; 6%) were the reasons for the withdrawn of BA. Among the serious adverse events, multiple sclerosis was registered after 6 years of abatacept using (the relationship with the drug used has not been proven), pregnancy in the 3rd year of adalimumab use (interruption at 16 weeks); serious local reaction after etanercept using– 1; infusion reactions (1-rituximab, 2-infliximab); uveitis de novo (2- etanercept).Conclusion:JPsA is one of the most severe variants of JIA, characterized by a high proportion of serious comorbid conditions, the development of refractoriness and adverse events of BA therapy (including uveitis, multiple sclerosis), requiring switching to line 2 and 3 with a limited choice of BA with pediatric indications. Special study requires the manifestation of psoriasis de novo mainly developed during TNF-monoclonal antibodies therapy.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is one of the frequent causes of the pulmonary arterial hypertension (PAH) which found in 6-15% patient with SSc. Patients with PAH, associated with SSc have a poorer prognosis than other forms of PAH. 6 World Symposium of PH lowered diagnostic cut-off to 21 mm Hg in hope of improved survival. PAH reversibility is described in congenital heart defects, HIV and some tumorsObjectives:The aim of the study to detect reversibility of PAH associated with SSc.Methods:Hemodynamics (mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), cardiac output (CO) and pulmonary vascular resistance (PVR)), functional class (NYHA), 6-minute walk distance (6MWD), biomarkers and DLCO were assessed. Patients with pulmonary fibrosis and left heart diseases were excluded.Results:The study includes 56 patients receiving start-up monotherapy with 1st generation PAH-specific drugs: bosentan (25 patients) and sildenafil (31 patients). The median age of the patients was 51.5 (37; 58) years. At the time of diagnosis, the MPAP in the sildenafil group was 49 (30; 50) mm Hg, bosentan - 50 (42; 56) mm Hg, differences not significant (p = 0.11). During observation against the background of sildenafil intake, the MPAP decreased by -3 (-7; 0) mm Hg, bosentan -6 (-13; -2) mm Hg. Decreasing of MPAP ≤ 21 mm Hg was at seven patients receiving sildenafil. Initial hemodynamic values in this group of patients was MPAP 25 (21; 27) mm Hg., RAP 2 (1; 5) mm Hg, PAWP 7 (6; 10) mm Hg., CV 5.9 (4.7; 6.7) l/min, PVR 3.0 (1.5; 4.2) Wood Unit. Among patients taking sildenafil, there were seven who had MPAP less than 35 mmHg, and among patients taking bosentan, there were 4 patients with less than 35 mmHg. However, the decreasing was observed only group who received sildenafil. ROC – analysis shown that cut-off for reversible is 29 mm Hg (AUC 0,977, sensitivity 97%, and specificity 100%)Conclusion:In patients with PAH, associated with SSc, on sildenafil treatment, at MPAP < 29 mm Hg reversibility is possible. Further study is required.Disclosure of Interests:None declared

Background:Juvenile Idiopathic Arthritis (JIA) is heterogeneous group of diseases which may include genetically determined conditions. Extremely rare monogenic hereditary autoinflammatory disease, such as Blau syndrome (BS) is usually difficult to recognize and JIA is initially established. BS is caused by a mutation in the NOD2/CARD5 gene and phenotypically characterized by triad of granulomatosis polyarthritis, uveitis and skin rash.Objectives:To present the family case of genetically confirmed BS in 2 siblings, initially diagnosed as patients with JIA.Methods:Two brothers of 15 and 3 years old were examined in our clinic. Additional genetic assay was performed because of unusual clinical picture.Results:Case report.Older brother, 15 y.o. developed arthritis of both wrist joints at the age of two. There was erythematous maculo-micropapular scaly rash on the trunk and extremities before the onset of arthritis. By 2009 (5 y.o.), the knees, ankles, and three PIP joints of the left hand were involved. Polyarthritis was characterized by severe effusion and periarticular tissues swallowing. He was treated in regional hospital by NSAID, methotrexate, cyclosporine A without significant positive effect. Since 2012 etanercept was added for treatment with variable result. Inactive status of the disease is never reached. Repeated intra-articular GC injections were needed from 4 to 10 times per year. The patient was admitted to our clinic in November 2019. He was suffering from severe polyarthritis and uveitis de novo (granulomatous chorioretinitis) was detected. At the same time his younger 3 y. o. brother with recently started disease was hospitalized in our clinic. He had polyarthritis with typical features of “boggy” synovitis and tenosynovitis of wrists, ankles and knees, anterior uveitis was determined. The onset of arthritis was preceded by a small-spotted rash with desquamation. This classical clinical features in younger brother let us suggest the BS. There was no increasing of ESR and CRP in both sibs throughout the course of the disease. A molecular genetic study of the NOD2/CARD15 gene in both brothers revealed the same mutation of c.1001G>A (p. Arg334Gln). Because of the absence of specific treatment for this disease and due to insufficient effect of etanercept with uveitis de novo therapy was changed to golimumab and good initial effect is reached. The youngest brother has started his therapy by methotrexate. It should be noted that the family has the eldest brother (20 y.o.), who has been suffering from arthritis since an early childhood with similar clinical picture. We are going to perform genetic analysis of the NOD2/CARD15 gene for the eldest brother.Conclusion:Our clinical case shows that extremely rare BS may be misdiagnosed as JIA. Lack of efficacy of the etanercept therapy and uveitis de novo developing may be caused by genetic (non-idiopathic) nature of disease. Classic triad of boggy-arthritis, granulomatous uveitis and/or skin lesions without acute phase markers is required to perform genetic assay for the detection of a pathogenic mutation of the NOD2/CARD15 gene. This case is remarkable by the presence of BS in two (or 3) children of the family.References:[1]Wouters C.H, Maes A, Foley K, et al. Blau Syndrome, the prototypic auto-inflammatory granulomatous disease. Pediatric Rheumatology. 2014; 12: 33.Disclosure of Interests:None declared

Background:Juvenile-onset SLE (jSLE) is a more aggressive disease than in adults due to several reasons including cognitive dysfunction, significantly affected the compliance and social rehabilitation of patients (pts).Objectives:To analyze the cognitive, emotional and communicative status of pts with jSLE.Methods:The study included 31 pts (90.3% girls) with jSLE, verified in accordance to SLICC criteria 2012. All pts underwent standard examination in accordance with the diagnosis; in case of suspected neuropsychiatric disorders pts were examined by a neurologist, psychiatrist. Classifying of neuropsychiatric disorders was performed in accordance with the recommendations of the ACR,1999. SLEDAI 2К was used for disease activity assessment. All pts were examined by a clinical psychologist using the standard pathodiagnostic testing.Results:The median age at the onset was 12.0 y.o. [10.6;14.5]. The median disease duration at the time of diagnosis - 0.75 ys [0.5;2.1]. 35.5% pts had neuropsychic disorders at the onset: psychoses – 12.9%, headaches – 12.9%, cognitive disorders – 19.4%, mood disorders – 16.1%, distal polyneuropathy – 12.9%. MRI of the brain was performed in 15 pts: CNS vasculitis was diagnosed in 3 pts (2 – with psychosis, 1 – with cognitive impairment). Median disease activity by SLEDAI at the time of diagnosis was 15 scores [10;23].At the time of examination by the clinical psychologist, the median age of pts was 15.2 ys [12.9;16.5]. The median disease duration was 1.1 ys [0.6;3.8]. Cognitive disorders were detected in 96.8% of the pts. The auditory-speech short-term memory was distributed between the medium and high levels (54.8% and 45.2%, respectively), and the high level of memorization prevailed in the long-term memory (67.7% high, 32.3% medium). A high level of indirect memory was revealed in 67.8% of pts, medium - in 25.8%, and low - in 6.4%. Distribution of the difficulties of attention were identified (64.5% - uneven distribution, 35.5% - sufficient distribution), as well as increased attrition of attention (74.2% - attrition is detected, 25.8% - no attrition). 58.1% of pts demonstrated a high level of inclusion into work, 41.9% - a low one. Concentration of attention was recognized as sufficient in 87.1% of pts, insufficient in 12.9%. The effectiveness of attention was rated as good in 87.1%, decreased – in 12.9%; stability is sufficient - in 64.5%, low - in 35.5%. In the operational side of thinking, a decrease in the level of generalization was revealed (48.4%); there were no disturbances in the motivational component, lability of thinking in the dynamic (12.9%). Various neurotic fears are characteristic for 54.8% of pts; the level of personal anxiety was increased in 41.9%, moderate - in 48.4%, low - in 9.7%. Signs of aggression were revealed in 19.4% of pts, a decrease in the level of social adaptation - in 51.6%. Communication difficulties experienced 83.9% of pts. According to the results of the clinical conversation, attention was focused on availability of conflict situations with peers in the disease onset in 38.7% of pts.Conclusion:Cognitive disorders were detected in the majority of pts with jSLE, regardless of the presence of neuropsychiatric disorders at the onset. The revealed features of the clinical and psychological status of pts with jSLE must be considered when working out an individual rehabilitation model and develop psycho-correctional programs.Disclosure of Interests:None declared

Background:Rituximab (RTX) is now approved only for pediatric patients (pts) 2 years of age and older with granulomatosis with polyangiitis or microscopic polyangiitis, but it has been used with success to treat another rheumatic diseases (RD) in children despite the status “of label”.Objectives:to analyze the safety of RTX in children with various RD who did not respond to conventional therapy.Methods:In our retrospective study safety data was analyzed for all pts, who received at least one infusion of RTX. The dose of RTX was established as 375 mg/m2of body surface area, administered by intravenous infusion once weekly for 1 to 4 weeks, depending on the CD19 lymphocyte count.Results:81 patients with RD, who received RTX, were included: 38 (46.9%) with systemic lupus erythemathosis (SLE), 16 (19.75%) – JIA, polyarthritis (2 pts - RF negative, 14 - RF positive), 9 (11.1%) - systemic JIA (sJIA), 6 (7.4%) –systemic sclerosis (SSc), 5 (6.2%) –primary Sjogren’s syndrome (pSS), 2 (2.5%) -juvenile dermatomyositis(JDM), 4 (4.9%) - mixedconnective tissue disease (MCTD) and 1 withlivedoid vasculitis(LV). Most were female – 69 (85.2%). The median age at onset – 11.6 years [interquartile range (IQR) 7.9; 14.3], median age of the starting therapy - 15.2 [IQR 12.5; 16.85] and median disease duration - 2.8 [IQR 1.0; 4.6]. 53 pts (65.4%) reported more than one course of RTX, maximum - 10. The median time between each course was 182 days [IQR 156–315]. The RTX was effective in 95% pts, ineffective in 5% (2 pts with sJIA, 2 pts with SLE and macrophage activation syndrome (MAS)). Adverse events (AE) were recorded in 23 (28.4%) pts, included upper respiratory tract infections – 7 (8.6%), urinary tract infections – 2 (2.5%), short-term infusion reactions that did not require discontinuation of therapy – 2 (2.5%), clinically insignificant neutropenia (grade I-II) – 4 (4.9%), decrease of IgG level was detected in 14 (17.5%) pts (median 5.5 g/l [IQR 4.0; 6.9]). The infection rate in pts with a low IgG level was 35.7%, in pts with neutropenia wasn’t recorded. Serious AE were recorded in 16 (19.7%) pts: sepsis – 4, pneumonia – 3, herpes zoster – 1, serious infusion reactions – 2, serious postinfusion reactions within 3 to 10 days – 4 (3 – MAS, 1 – hemorrhagic vasculitis), death – 2 pts with SLE and MAS (therapy of RTX was inefficiency). In general, various AE were registered in 55.6% of pts with sJIA, in 52.6% of pts with SLE, 50% of pts with SSc and JDM, and 80% of pts with pSS. Discontinuation of therapy due to SAE was observed in 15 pts (18.5%).Conclusion:Our study demonstrated that RTX is highly effective in children with RD, the majority with SLE, but the safety data obtained indicate the need for careful monitoring of therapy, primarily taking into account the frequency of infections. A decrease in IgG level was observed in a small proportion of pts and did not correlate with the incidence of infections. The frequency of serious infections was low.Disclosure of Interests:None declared

IntroductionAutoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting.MethodsThe ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an ‘observer-nested-within-subject’ design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach’s alpha.ResultsThe ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items.ConclusionThe ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.

ObjectiveThis report aims to determine the safety, pharmacokinetics (PK) and efficacy of subcutaneous golimumab in active polyarticular-course juvenile idiopathic arthritis (polyJIA).MethodsIn this three-part randomised double-blinded placebo-controlled withdrawal trial, all patients received open-label golimumab (30 mg/m2 of body surface area; maximum: 50 mg/dose) every 4 weeks together with weekly methotrexate during Part 1 (weeks 0–16). Patients with at least 30% improvement per American College of Rheumatology Criteria for JIA (JIA ACR30) in Part 1 entered the double-blinded Part 2 (weeks 16–48) after 1:1 randomisation to continue golimumab or start placebo. In Part 3, golimumab was continued or could be restarted as in Part 1. The primary outcome was JIA flares in Part 2; secondary outcomes included JIA ACR50/70/90 responses, clinical remission, PK and safety.ResultsAmong 173 patients with polyJIA enrolled, 89.0% (154/173) had a JIA ACR30 response and 79.2%/65.9%/36.4% demonstrated JIA ACR50/70/90 responses in Part 1. At week 48, the primary endpoint was not met as treatment groups had comparable JIA flare rates (golimumab vs placebo: 32/78=41% vs 36/76=47%; p=0.41), and rates of clinical remission were comparable (golimumab vs placebo: 10/78=12.8% vs 9/76=11.8%). Adverse event and serious adverse event rates were similar in the treatment groups during Part 2. Injection site reactions occurred with ConclusionAlthough the primary endpoint was not met, golimumab resulted in rapid, clinically meaningful, improvement in children with active polyJIA. Golimumab was well tolerated, and no unexpected safety events occurred.Clinical Trial RegistrationNCT01230827; Results.

ObjectivesAutoinflammatory diseases cause systemic inflammation that can result in damage to multiple organs. A validated instrument is essential to quantify damage in individual patients and to compare disease outcomes in clinical studies. Currently, there is no such tool. Our objective was to develop a common autoinflammatory disease damage index (ADDI) for familial Mediterranean fever, cryopyrin-associated periodic syndromes, tumour necrosis factor receptor-associated periodic fever syndrome and mevalonate kinase deficiency.MethodsWe developed the ADDI by consensus building. The top 40 enrollers of patients in the Eurofever Registry and 9 experts from the Americas participated in multiple rounds of online surveys to select items and definitions. Further, 22 (parents of) patients rated damage items and suggested new items. A consensus meeting was held to refine the items and definitions, which were then formally weighted in a scoring system derived using decision-making software, known as 1000minds.ResultsMore than 80% of the experts and patients completed the online surveys. The preliminary ADDI contains 18 items, categorised in the following eight organ systems: reproductive, renal/amyloidosis, developmental, serosal, neurological, ears, ocular and musculoskeletal damage. The categories renal/amyloidosis and neurological damage were assigned the highest number of points, serosal damage the lowest number of points. The involvement of (parents of) patients resulted in the inclusion of, for example, chronic musculoskeletal pain.ConclusionsAn instrument to measure damage caused by autoinflammatory diseases is developed based on consensus building. Patients fulfilled a significant role in this process.

Objective To evaluate genetic, demographic and clinical features in patients with cryopyrin-associated periodic syndrome (CAPS) from the Eurofever Registry, with a focus on genotype-phenotype correlations and predictive disease severity markers. Methods A web-based registry retrospectively collected data on patients with CAPS. Experts in the disease independently validated all cases. Patients carrying NLRP3 variants and germline-mutation-negative patients were included. Results 136 patients were analysed. The median age at disease onset was 9 months, and the median duration of follow-up was 15 years. Skin rash, musculoskeletal involvement and fever were the most prevalent features. Neurological involvement (including severe complications) was noted in 40% and 12% of the patients, respectively, with ophthalmological involvement in 71%, and neurosensory hearing loss in 42%. 133 patients carried a heterozygous, germline mutation, and 3 patients were mutation-negative (despite complete NLRP3 gene screening). Thirty-one different NLRP3 mutations were recorded; 7 accounted for 78% of the patients, whereas 24 rare variants were found in 27 cases. The latter were significantly associated with early disease onset, neurological complications (including severe complications) and severe musculoskeletal involvement. The T348M variant was associated with early disease onset, chronic course and hearing loss. Neurological involvement was less strongly associated with V198M, E311 K and A439 V alleles. Early onset was predictive of severe neurological complications and hearing loss. Conclusions Patients carrying rare NLRP3 variants are at risk of severe CAPS; onset before the age of 6 months is associated with more severe neurological involvement and hearing loss. These findings may have an impact on treatment decisions.

Objective.Abatacept (ABA) has recently been proposed as second-line treatment in patients with juvenile idiopathic arthritis (JIA)–associated uveitis refractory to anti–tumor necrosis factor-α (anti-TNF) agents, but little is known about its efficacy as a first-line approach. The aim of the present study was to compare the safety and efficacy of ABA as a first-line biological agent (ABA-1) with that of ABA as a second-line treatment after 1 or more anti-TNF agents (ABA-2), in patients with severe JIA-related uveitis.Methods.In this multicenter study, we collected data on patients with severe JIA-related uveitis treated with ABA as a first-line or second-line biological agent. Changes in frequency of uveitis flares/year and ocular complications before and after ABA treatment, clinical remission, and side effects were recorded.Results.Thirty-five patients with a mean age of 10.8 years were treated with ABA for a mean period of 19.6 months. In 4 patients, ABA administration was discontinued, owing to inefficacy on arthritis in 3 cases and allergic reaction in 1. Thirty-one patients, 14 in the ABA-1 group and 17 in the ABA-2 group, completed the 12-month followup period; of these, 17 (54.8%) had clinical remission. The mean frequency of uveitis flares decreased from 4.1 to 1.2 in the ABA-1 group (p = 0.002) and from 3.7 to 1.2 in the ABA-2 group (p = 0.004). Preexisting ocular complications improved or remained stable in all but 5 patients, all in the ABA-2 group. No significant difference was found between the efficacy of the 2 treatment modalities. ABA confirmed its good safety profile.Conclusion.ABA, used as first-line biological treatment or after 1 or more anti-TNF agents, induces a comparable improvement in severe refractory JIA-related uveitis.

Objective.The main objective was to determine the 2-year clinical benefit and safety of etanercept (ETN) in children with the juvenile idiopathic arthritis (JIA) categories of extended oligoarthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA).Methods.CLIPPER was a 96-week, phase IIIb, open-label, multicenter study. Patients with eoJIA, ERA, or PsA received ETN 0.8 mg/kg once weekly (50 mg max) for up to 96 weeks. The proportions of patients reaching the JIA American College of Rheumatology (ACR) 30/50/70/90/100 and inactive disease responses at Week 96 were calculated. Adverse events (AE) were collected throughout the study (intention-to-treat sample).Results.There were 127 patients (eoJIA n = 60, ERA n = 38, PsA n = 29) who received ≥ 1 dose of ETN. The mean disease duration was 31.6 (eoJIA), 23.0 (ERA), and 21.8 (PsA) months. At Week 96, JIA ACR 30/50/70/90/100/inactive disease responses (95% CI) were achieved by 84.3% (76.7, 90.1), 83.5% (75.8, 89.5), 78.7% (70.6, 85.5), 55.1% (46.0, 63.9), 45.7% (36.8, 54.7), and 27.6% (20.0, 36.2) of patients, respectively. The most common AE (no. events, events per 100 patient-yrs) overall were headache (23, 10.7), pyrexia (12, 5.6), and diarrhea (10, 4.6). The most common infections were upper respiratory tract infection (83, 38.6), pharyngitis (50, 23.2), gastroenteritis (22, 10.2), bronchitis (19, 8.8), and rhinitis (17, 7.9). No cases of malignancy, active tuberculosis, demyelinating disorders, or death were reported.Conclusion.Over 96 weeks of therapy, ETN demonstrated sustained efficacy at treating the clinical symptoms of all 3 JIA categories, with no major safety issues.

Objective In an international, multicenter, double-blind, randomized clinical trial we evaluated the short-term (3 months) and long-term (12 months) efficacy and safety of 2 different doses of meloxicam oral suspension compared with the efficacy and safety of naproxen oral suspension in children with oligoarticular-course (oligo-course) or polyarticular-course (poly-course) juvenile idiopathic arthritis (JIA). Methods Children ages 2–16 years who had active oligo-course or poly-course JIA and who required therapy with a nonsteroidal antiinflammatory drug were eligible for this trial. Patients were randomly allocated to receive therapy with meloxicam oral suspension, 0.125 mg/kg body weight in a single daily dose; meloxicam oral suspension, 0.25 mg/kg body weight in a single daily dose; or naproxen, 10 mg/kg body weight in 2 daily doses. The trial drugs were administered in a double-blind, double-dummy design for up to 12 months. Response rates were determined according to the American College of Rheumatology pediatric 30% improvement criteria (ACR pediatric 30). Safety parameters were assessed by evaluating the frequency of adverse events in the 3 groups. Results Of 232 patients enrolled, 225 received treatment, 6 were not eligible for randomization, and 1 randomized patient was not treated. One hundred eighty-two patients (81%) completed the 12-month treatment period. Response rates according to the ACR pediatric 30 criteria improved from month 3 to month 12, as follows: from 63% to 77% in the meloxicam 0.125 mg/kg group, from 58% to 76% in the meloxicam 0.25 mg/kg group, and from 64% to 74% in the naproxen group. No statistically significant differences in response rates were observed between the groups. There were no differences in the frequency of adverse events or abnormal laboratory values between the 3 groups. Conclusion The short- and long-term safety and efficacy of meloxicam oral suspension appear to be comparable with the safety and efficacy of naproxen oral suspension in the treatment of oligo-course and poly-course JIA. The once-daily administration of meloxicam oral suspension might represent an improvement in the treatment of JIA.

A distinctive feature of systemic juvenile idiopathic arthritis (sJIA) is its high resistance to therapy of DMARDs and biologics (B) used as the 1st line before the advent of IL-1 and IL-6 inhibitors.

Biologics are often used in therapy of DMARDs resistant JIA. The most complicated problem is choosing specific biological agent in particular case. AntiTNF inhibitors are well studied, but the application of Abatacept in real clinical practice hasn't been investigated enough.

Background Interleukin-1 inhibitor Canakinumab (a humanized anti- Il-1β monoclonal antibody) is gaining wider use in Russian clinical practice recently for treatment of auto-inflammatory diseases (AIDs). Experience with Canakinumab for systemic juvenile idiopathic arthritis (SoJIA), considered as AIDs, is being accumulated as first and second line biologic agents therapy. In Russia Canakinumab was initially marketed in 2011 for cryopyrin-associated periodic syndromes (CAPS), in 2013 – for SoJIA. Objectives To assess efficacy and tolerability of Canakinumab in AIDs and SoJIA patients in clinical practice. Methods Use Canakinumab at our Institute was commenced in 2012 y. The study included 19 pts, among them 12 had AIDs (including CAPS – in 8 pts: MWS – in 6, and CINCA/NOMID- in 2 pts; TRAPS - in 3 pts; Schnitzler syndrome – in 1), 7 pts had SoJIA. Among AIDs pts there were 7 females and 5 males, 9 pediatric and 3 adult pts, 2 pts from pediatric population getting adult by the time of analysis. Mean AIDs pts age at inclusion was 18,6 y (3–44), infantile disease onset was recorded in 9 pts, in 6 out of them – it was a neonatal onset from the moment of birth. Two familial MWS cases were included. Disease duration ranged from 3 to 44 years. Genetic mutations were established in 9 pts, including: gene NLRP3- 6 (Thr436Ile, Thr438Ile, Thr350Met – in 4 pts (two familial cases)), gene TNFRSF1A - 3 (His51Tyr, Cys59Arg, Cys99Arg). All AIDs pts presented with rash, fever, conjunctivitis or uveitis (8), neurosensory deafness (4), arthritis symptoms (9), lymphadenopathy (7), CNS involvement in 2, abdominal pain (5), stomatitis (4), physical retardation in CINCA/NOMID pts, intellectual retardation and cognitive impairment in 1 patient. SoJIA pts were aged 3,5 -17,5 y.o. predominantly males (5), with disease duration 1 - 16 y. All pts presented with systemic manifestations, 4 pts had severe polyarthritis. Increased levels of acute phase markers were documented in all pts. Canakinumab efficacy was estimated based on changes in ESR, CRP and WBC count vs baseline. Results Canakinumab was administered s/c at 2–4mg/kg (max 150 mg) once every 8 weeks in AIDs pts, and at 4–6mg/kg (max 300mg) once in every 4 weeks in SoJIA pts. Canakinumab therapy duration in AIDs pts varied from 3mo to 2,5y, in SoJIA pts – from 9mo to 4y. Rapid clinical improvement was documented in all pts, with resolution of systemic manifestations and normalizing levels of acute phase markers. Prolonged ESR and CRP normalization was observed in one CINCA/NOMID patient. In 4 SoJIA pts arthritis manifestations were not sufficiently controlled. Canakinumab tolerability was satisfactory in all AIDs and SoJIA pts. No serious adverse reactions were documented. Canakinumab discontinuation in one SJIA patient was associated with secondary drug failure and onset of macrophages activation syndrome (MAS). Conclusions The single Federal Center experience with Canakinumab in clinical practice in AIDs and SoJIA pts demonstrated high efficacy and good tolerability of this medication. No serious adverse events were noted. In SoJIA pts Canakinumab use should be viewed as possible option at early stages of the disease with systemic and initial joint involvement, whilst efficacy in pts with advanced arthritis turned out to be insufficient. Disclosure of Interest None declared

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2014-02-26T17:28:15Z No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Made available in DSpace on 2014-02-26T17:28:15Z (GMT). No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Previous issue date: 2007-02-15 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:29:57Z No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Made available in DSpace on 2014-05-20T15:29:57Z (GMT). No. of bitstreams: 1 WOS000244138100006.pdf: 158213 bytes, checksum: ebf0e660bfdbefc0e3aceeba876f1006 (MD5) Previous issue date: 2007-02-15 Objective. To investigate the proxy-reported health-related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA).Methods. In this multinational, multicenter, cross-sectional study, HRQOL of patients with JIA was assessed through the Child Health Questionnaire (CHQ) and was compared with that of healthy children of similar age from the same geographic area. of joint inflammation, Childhood Health Assessment Questionnaire (CHAQ), and erythrocyte sedimentation rate.Results. A total of 6,639 participants (3,324 with JIA and 3,315 healthy) were enrolled from 32 countries. The mean SD physical and psychosocial summary scores of the CHQ were significantly lower in patients with JIA than in healthy children (physical: 44.5 +/- 10.6 versus 54.6 +/- 4.0, P < 0.0001; psychosocial: 47.6 +/- 8.7 versus 51.9 +/- 7.59 P < 0.0001), with the physical well-being domain being most impaired. Patients with persistent oligoarthritis had better HRQOL compared with other subtypes, whereas HRQOL was similar across patients with systemic arthritis, polyarthritis, and extended oligoarthritis. A CHAQ score > 1 and a pain intensity rating > 3.4 cm on a 10-cm visual analog scale were the strongest determinants of poorer HRQOL in the physical and psychosocial domains, respectively.Conclusion. We found that patients with JIA have a significant impairment of their HRQOL compared with healthy peers, particularly in the physical domain. Physical well-being was mostly affected by the level of functional impairment, whereas the intensity of pain had the greatest influence on psychosocial health. Univ Genoa, Pediat Rheumatol Int Trials Org, IRCCS G Gaslini, I-16147 Genoa, Italy IRCCS G Gaslini, Serv Epidemiol & Biostat, Genoa, Italy Hop Necker Enfants Malad, Paris, France Univ Estadual Paulista, Botucatu, SP, Brazil Princess Margaret Hosp Children, Perth, WA, Australia Hanyang Univ, Med Ctr, Hosp Rheumat Dis, Seoul 133791, South Korea Univ Ziekenhuis Gent, Ctr Kinderreumatol, Ghent, Belgium Allgemeines Krankenhaus Eilbeck, Hamburg, Germany Inst Nacl Rehabil, Mexico City, DF, Mexico Wilhelmina Childrens Hosp, Utrecht, Netherlands Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland Fac Med 1, Prague, Czech Republic Gen Fac Hosp, Prague, Czech Republic Inst Madrileno Salud, Madrid, Spain Aristotle Univ Thessaloniki, Ippokration Gen Hosp, Thessaloniki, Greece Hop Univ Geneva, Geneva, Switzerland RAMS, Inst Rheumatol, Moscow, Russia Cerrahpasa Tip Fak, Istanbul, Turkey Cleveland Clin Fdn, Cleveland, OH 44195 USA HealthActCHQ, Boston, MA USA Univ Genoa, IRCCS G Gaslini, Genoa, Italy Univ Estadual Paulista, Botucatu, SP, Brazil

Background FMF has been reported to be frequently combined with rheumatic diseases also underlane by in inflammatory process. Objectives To describe the cases of FMF comorbid with rheumatic diseases in children of the Russian population followed up in Federal Rheumatologic Centers. Methods All the patients with periodic fever diagnosed as FMF who had been consulted in “Nasonova Research Institute of Rheumatology” from 2008 to 2014 were included in the study. The diagnosis of FMF was verified by Livneh criteria. Comorbid rheumatic diseases were diagnosed according to the criteria generally accepted in pediatric rheumatology. As a standard in pediatric rheumatology, coding sequences of MEFV gene were analyzed by direct automatic sequencing in all the patients (investigation of “hot spots” or complete genome analysis). Results FMF was diagnosed in 13 children, 9 girls and 4 boys. Average age of the onset was 7.0±4.4 years. Most patients (11) were the Armenians and 2 patients were related to the peoples of the Northern Caucasus. In 5 patients (38.5%) the disease combined with rheumatic pathology: oligoarticular juvenile arthritis in 2 patients; chronic recurrent multifocal osteomyelitis in 1 patient; acute rheumatic fever in 1 patient and two diseases, juvenile ankylosing spondylitis and Henoch-Schonlein hemorrhagic vasculitis, in 1 patient. In all the comorbid patients FMF diagnosis was verified by the detection of MEFV gene mutation: 3 homozygotes by M694V mutation, 2 compound heterozygotes M694V/V726A and M694V/M680I. The comorbid patients included 2 boys and 3 girls. Four of these patients developed rheumatic diseases on the background of FMF and 1 patient developed FMF after the attack of acute rheumatic fever. The age of FMF onset in the comorbid patients was 1 to 11 years, mean age was 7.75 years. The onset of concomitant rheumatic diseases was at the age of 5 to 11 years, mean age was 9 years; the interval between the onset of FMF and rheumatic disease was 1 month to 9 years. Concomitant rheumatic pathology developed in two patients treated with colchicine. The therapy with TNF inhibitors (Etanercept) was administered to the two patients with FMF and juvenile arthritis. Conclusions The patients with FMF in the Russian population quite often have concomitant rheumatic pathology. FMF may be combined with two rheumatic diseases in the same patient. Adequate colchicine therapy does not prevent the development of concomitant rheumatic disease. References Demirkaya E, Ozen S, Bilginer Y. et al The distribution of juvenile idiopathic arthritis in the eastern Mediterranean: results from the registry of the Turkish Paediatric Rheumatology Association. Clin Exp Rheumatol. 2011;29(1):111-6. Bayram C, Demircin G, Erdogan O et al. Prevalence of MEFV gene mutations and their clinical correlations in Turkish children with Henoch-Schonlein purpura. Acta Paediatr. 2011;100(5):745-9. Keles I, Aydin G, Tosun A et al Familial Mediterranean fever and ankylosing spondylitis in a patient with juvenile idiopathic arthritis: A case report and review of the literature. Rheumatol Int. 2006;26(9):846-51. Livneh A, Langevitz P, Zemer D et al. Criteria for the diagnosis of familial Mediterranean fever. Artritis Rheum, 1997; 40(10):1897-188. Disclosure of Interest None declared

Objectives To assess the value of rituximab (RTM) in a limited series of patients (pt) with juvenile systemic sclerosis (jSSc). Methods Three patients with jSSc were evaluated: 2 girls (ptA and ptB), 1 boy (ptC) with onset at 7, 8 and 7 years, and duration of the disease at the beginning of therapy 4, 6 and 7 years, all with diffuse form of jSSc. Patients had a high activity and aggressive course of the disease with predominant pulmonary (interstitial lung disease – ptA, ptB), heart (ptC), microcirculatory disturbances (ptA, ptB), typical and severe skin lesions and musculoskeletal system, immunological activity (ANA “+” - all, aScl70 “+” - ptA and ptB, ACA “+” – ptC). Therapy, previous RTM, included corticosteroids, cyclophosphamide, blockers ACE alprostadil. They received RTM at a dose of 375 mg/m 2 every 6 months; ptA received 4 infusions, pnB – 3, ptC – 6, with a total duration of use of RTM 24, 18 and 36 months. The use of RTM approved by local ethics committee. Results Improvement was noted in all patients. The first manifestations of improvement established after 6 months of the RTM treatment with subsequent increase. All patients showed marked improvement in health, increased exercise tolerance, reduction of skin tightening (after 6 months of therapy there was a decrease of the Rodnan total skin thickness score, 6 points; with a further decrease in accordance with the duration of the treatment), sclerodactyly, improving joint function (polyarthropathies), a gradual increase in DLCO, FVC (6-8%), indicators of heart disease (ptC, with a dominant extremely serious cardiac disease, reducing the size of the left ventricular end-diastolic dimension, from 58 to 52 mm, increase in ejection fraction from 32 to 48%, reducing the number of ventricular ectopic beats per day from 19,657 to 1,671). During the period of treatment revealed no significant adverse events associated with the use of rituximab. Conclusions The results of our observations of small number of patients with severe jSSc who had RTM therapy suggests that the use of RTM is a promising treatment for jSS with the presence of a good therapeutic effect, with an acceptable adverse event profile, reduces the need for glucocorticoids, limit the use of cytotoxic drugs. Further studies of the efficacy of this therapy in the treatment of jSSc are needed. Disclosure of Interest None declared

Background Biologic agents have improved the possibility of treatment of juvenile idiopathic arthritis (JIA). Infliximab has the longest history of using and despite of off-label status was administrated from 2004. Etanercept is available in Russia from 2009. Unfortunately some patients do not respond to them or have side effects. Drug survival is a general marker of the success of a treatment, as it depends on the drug efficacy and its side effects. Objectives To evaluate drug survival (continuation rates on drug) of Biologic agents (BA) in JIA patients (pts), non-responders to conventional therapy DMARDs included. Methods The study involved a prospective cohort of JIA patients taking different BA who attended our clinic from 2004 to 2014 with at least one year follow-up. Data on the disease course were used to estimate drug survival with Kaplan-Meier and calculate adverse event (AE) rates. Results A number of 431 JIA pts, treated with one or more BA were analyzed. The average age of patients is 10,5 years (from 1,5 to 18 years). Median disease duration, from onset to the beginning of BA therapy was 7.1 years (interquartil range 1.3 -14.1). In total, 543 treatment series with etanercept (n=155), adalimumab (n=141), infliximab (n=117), abatacept (n=77), tocilizumab (n=53) were administered. There were 131 cases of BA withdrawals. Reasons for drug discontinuation were inefficacy 42% (etanercept 5%, infliximab 17%, adalimumab 5%, abatacept 13%, tocilizumab 1%), AE 33% (etanercept 5%, infliximab 20%, adalimumab 2%, abatacept 2%, tocilizumab 4%) or other 24% (etanercept 2%, infliximab 11%, adalimumab 10%, abatacept 1%, tocilizumab 2%). Etanercept treatment survival at 12 months was 98%, infliximab - 80%, adalimumab - 93%, abatacept – 89%, tocilizumab – 91%. Data is presented on diagram below. Highest survival rates for TNF-inhibitors are associated with juvenile spondiloarthritis (JSA) group patients (Infliximab 64%, Adalimumab 89%, Etanercept 91%) and lowest with systemic arthritis (Infliximab 19%, Adalimumab 22%, Etanercept 78%). Conclusions Infliximab therapy associated with the most discontinuation rate due to adverse events and inefficacy in compare of other BA. Among the subtypes of JIA, the risk of treatment discontinuation, TNF-inhibitors mostly, was highest in systemic arthritis. On the contrary, in JSA group patients the discontinuation rate was markedly low. In whole cohort of JIA patients etanercept and adalimumab have the optimal drug survival profile. Disclosure of Interest None declared

Early onset of juvenile idiopathic arthritis (eoJIA) associated with pauci?polyarthicular joints involvement, antinuclear factor and uveitis is a special subtype of JIA. Generally accepted opinion of pediatric rheumatologists this JIA category isn`t belong to ankylosing spondylitis (AS)-related group of diseases.

Methods In prospective study were included 45 pts(19b/26g) with sJIA refractory to conventional treatment, who was treated by TCZ from 9 months to 54 months. At baseline mean age of 6.25(2.0-17.8)yrs; mean disease duration of 4.5(0.315.9)yrs. TCZ used as the 1 B in 28 pts, 2 – in 12, 3 – in 5. 37.8% pts previously received B:TNF-ingibitors-17, abatacept–2, rituximab–3. 41 pts(91.1%) had arthritis at the baseline. Systemic features were observed in 40(88.9%) pts. Mean number of systemic manifestations(NSM) was 2.82 (1.5;6). 2 pts had MAS before of TCZ initiation. Retrospectively all pts were separated into the groups depending on the age of manifestation of disease (before 3 yrs/older 3 yrs -22/23), duration of disease (less than 3 yrs/more – 20/25), the number of active joints (less than 10/more–22/23), the number of active systemic features (NSM 0 – 13 pts, 1/2 10, 3/4 12, 5/6 – 10), and previous B (B-naive/previous B-28/17). Efficacy of TCZ therapy was evaluated in accordance to ACRpedi criteria in 1, 3, 6, 9, 12 and every 6 months of treatment later. Results 36 pts continue the treatment, mean duration 27.4 months(9;54). In 9 pts TCZ was cancelled due to serious adverse effects(5), another reasons(4). All pts achieved more than 30-50% improvement by ACRpedi criteria. We found no significant differences in efficacy parameters at the response to therapy depending on the investigated factors. However, pts who had early manifestation of disease, long disease duration, large NSM achieved good response on arthicular status more slowly. Also we observed some increasing of disease activity in all groups between 30-36 months of therapy. Steady improvement allowed to decrease prednisolone (PR) dose in all pts, to cancel PR in 19.4% pts, to cancel NSAIDs in 14% pts. 9 pts achieved inactive disease status. Adverse events were observed independently of investigated factors and included postinfusion reactions (vomiting-1, headache-2, sore throat-4, chestpain-4, blood pressure increasing-1, eczema-2), infections (upper respiratory infections-16, bronchitis-1, pneumonia-2, gastroenteritis-1, ears ’ infections-3, periodontitis-2), temporary laboratory abnormalities (neutropenia-21, thrombocytopenia-8, IgG decreasing -10, hyperbilirubinemia-3, elevated transaminases-7). We have observed some SAE: infusion reaction (5); severe infections – varicella (2), atypical pneumonia (1), tuberculosis(1). MAS observed in 4 pts (1-after respiratory infection, 1after elective surgery, 1-after increase interval between infusion more than 4 weeks, 1-unknown reason), in all case of MAS TCZ was continued.

Juvenile dermatomyositis (JDM) is a rare rheumatic disorder, often associated with poor functional outcome because of the high incidence of diffuse calcinosis in skeletal muscles, especially in case of late diagnosis.

According to the data found in the literature on clinical psychology, RA refers to the group of psychosomatic diseases, the leading role in occurrence of which is played by negative life events that cause stress.

Juvenile idiopathic arthritis is a heterogeneous group of chronic inflammatory diseases with high risk of progressive articular damage. Clinical examination is the basis for assessing of the affected joints. Modern radiological techniques provide additional important information about the status of the damaged joints, allow the identification of subclinical inflammation.

Background Elevated IL-6 levels are associated with disease activity in patients (pts) with juvenile idiopathic arthritis (JIA). 1 Tocilizumab (TCZ), an IL-6 receptor inhibitor, was evaluated for the treatment of polyarticular-course JIA (pcJIA; RF+ and RF– poly- and extended oligoarticular JIA) in the CHERISH study. Methods CHERISH is a 104-wk study in pts age 2-17 y with active pcJIA for ≥6 mo who failed MTX. Prior to wk 16, all pts received open-label (OL) TCZ every 4 wks (if body weight [BW] ≥30 kg, 8 mg/kg [n=119]; if BW Results 188 pts entered the OL lead-in period (77% female; 79%/46% receiving concurrent MTX/oral corticosteroids [CS], respectively). 22 (12%) pts withdrew from the OL extension (15 pts [8%] insufficient response; 3 [2%] adverse events [AEs]; 4 [2%] other reasons), and 166 pts entered the DB period. Efficacy responses at the end of the OL extension at wk 16 are shown (Table). At wk 40, the primary endpoint was met (48.1% PBO pts vs 25.6% TCZ pts), and JIA ACR30/50/70 responses were significantly higher with TCZ than PBO (Table). The degree of improvement at wk 16 was lower for these endpoints in the TCZ 8 mg/kg Image/graph Conclusions The CHERISH trial supports that TCZ treatment in pcJIA is efficacious and leads to a sustained clinically meaningful improvement with a monthly regimen at doses of 8 mg/kg if BW ≥30 kg and 10 mg/kg if BW 2 References Clin Exp Rheumatol . 1992;493; Ann Rheum Dis 2011;70(S3):67 Disclosure of Interest F. De Benedetti Grant/research support from: Abbott, Pfizer, BMS, Roche, Novimmune, Novartis, SOBI, N. Ruperto Grant/research support from: Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Consultant for: (fees received by organization) Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Speakers bureau: Abbott, Boehringer, BMS, Novartis, Astellas, Italfarmaco, MedImmune, Pfizer, Roche, Z. Zuber: None Declared, C. Keane Employee of: Roche, O. Harari Employee of: Roche, A. Kenwright Employee of: Roche, R. Cuttica Grant/research support from: Roche, Novartis, Lilly, Centocor, Consultant for: Roche, Novartis, Centocor, Pfizer, Speakers bureau: Roche, Pfizer, BMS, Novartis, V. Keltsev: None Declared, R. Xavier: None Declared, I. Calvo: None Declared, I. Nikishina: None Declared, N. Rubio-Perez: None Declared, E. Alekseeva: None Declared, V. Chasnyk: None Declared, J. Chavez: None Declared, G. Horneff Grant/research support from: Abbott, Pfizer, Speakers bureau: Abbott, Pfizer, Novartis, Roche, Chugai, V. Opoka-Winiarska: None Declared, P. Quartier Grant/research support from: Abbott, Novartis, Pfizer, Consultant for: Novartis, Abbott, Pfizer, BMS, Roche, C. Silva Grant/research support from: Roche, E. Silverman: None Declared, A. Spindler: None Declared, A. Martini Grant/research support from: Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Consultant for: (fees received by organization) Abbott, AstraZeneca, BMS, Centocor, Lilly, Francesco Angelini, GSK, Italfarmaco, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, Wyeth, Speakers bureau: Abbott, BMS, Astellas, Boehringer, Italfarmaco, MedImmune, Novartis, Pfizer, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: AstraZeneca, Centocor, Wyeth, Amgen, BMS, Abbott, Pfizer, Hoffmann-La Roche Novartis, UCB, Forest Research, H. Brunner Shareholder of: PRCSG, Grant/research support from: National Institutes of Health, Lupus Foundation, Cincinnati Center for Clinical and Translational Research, Consultant for: Roche, Novartis, GSK, Medimmune, Pfizer, BMS

Background Macrophage activation syndrome (MAS) is a severe complication of systemic juvenile idiopathic arthritis (sJIA) often leading to multiple organ failure. Biological agents including tocilizumab are used extensively in the treatment of JIA, but can trigger MAS development in some patients and therefore MAS is often considered as a contraindication to tocilizumab. We have experience of successful use of tocilizumab in sJIA complicated by MAS. Objectives Clinical narrative of MAS in two sJIA patients. Results A 10 year old boy has suffered from sJIA for over 2 years, presents with fever, serositis, lymphadenopathy, hepatomegaly, polyarthritis, leukocytosis 22×10 9 , CRP 120 g/L, ESR 64 mm/hr. Treatment with glucocorticoids (GCs), methotrexate, and cyclosporine A was inadequately effective. While on intravenous administration of methotrexate 30 mg the patient presented with persistent febrile hyperthermia, hepatosplenomegaly, nephritis, rapid decrease in ESR - 2 mm/hr, cytopenia (platelet count 116×10 12 , WBC 5.4×10 9 , HB 90 g/L), ferritin – 905 µg/L, transaminase increases (LDH - 723 U/L, ALT), increase in triglycerides, and decrease in fibrinogen. The use of methylprednisolone 15 mg/kg for 3 days, GCs, cyclosporine and administration of tocilizumab 10 mg/kg every 12 weeks resulted in MAS resolution. Normalization of LDH and ferritin was observed after the second administration of tocilizumab. A 3 year old girl with sJIA and primary hyperinsulinism has been ill for 1 year. Following 2-month therapy with IL-1 receptor antagonist anakinra 2-4 mg/kg she developed sJIA relapse (fever, rash, polyserositis, arthritis) with symptoms of MAS (uncontrolled fever, CNS lesion, nephritis, splenomegaly +10 cm, hepatomegaly, lymphadenopathy, ESR 10 mm/hr, thrombocytopenia 115×10 12 , anaemia - HB 89 g/l, ferritin >10000 µg/L, transaminase increases - LDH 1702 U/L, increase in triglycerides; coagulation disorders. Anakinra was discontinued, GCs were administered orally 1 mg/kg, following which the disease activity persisted but cytopenia resolved. After 2 weeks, tocilizumab 12 mg/kg iv once every 2 weeks was administered with favorable effect. Normalization of ferritin and LDH was achieved after the third administration of tocilizumab. No adverse events were observed. The both patients continue to receive tocilizumab infusions every 2 weeks with good therapeutic response corresponding to ACR70-90%. Conclusions Our experience with tocilizumab given in combination with GCs in patients with sJIA complicated by MAS showed its high efficacy and good tolerability superior to that of GCs alone. References Journal of Rheumatology.2011;38 Current Opinion inRheumatology. 2002;14 Disclosure of Interest None Declared

Background It is known that Tocilizumab (TCZ) is effective option in systemic Juvenile idiopathic arthritis (sJIA). NNZ had “off label” status for children in Russia till December 2011, but with Ethics Committee approvement it used in clinical practice for most seriously affected sJIA patients (Pts). Objectives To analyzed effects of TCZ on activity and other disease features in Ptswith active sJIA, who were received TCZ in our clinic from Nov 2009 to Jan 2012. Methods TCZ was indicate to 23 Pts with sJIA (11 boys, 12 girls; mean age of 8.96, range 1.6–17.6 yrs; mean disease duration of 5.5, range 0.3–11,75 yrs) who had persistent disease activity in spite of adequate treatment, included NSAID, steroids, DMARDs (methotrexate (MTX) alone–7; MTX in combination with cyclosporine or leflunomide–16). After starting TCZ therapy second DMARD was cancelled andMTX therapy was continued in all children. 9 Pts were previously treated by biologics (7- TNF-inhibitors; 2-rituximab). Ongoing steroids was used in 19 Pts (meanprednisone dose - 0.35mg/kg/day, range 0,11–0.68), NSAIDs recievedall Pts. At baseline 22 Pts had active arthritis (mean number of active joints 14, range 3–30), 18 - systemic features, all Pts had high laboratory activity (mean CRP 108.25 mg/l, range 14.9-223 mg/l). We began TCZ use in a dose of 8 mg/kg intravenously every 4 weeks according to indications for adult RA patients. At 7 Pts the disease flare has developed for 15-20 day after infusion, therefore an interval have reduced till 2 weeks, the dose has been increased to 10-12 mg/kg. Results The ACR Pedi 30,50,70,90 responds were achieved by 96%,48%,9%,0% of Pts at Week 4 (n=23), by 87%,87%,40%,7% at Week 12 (n=12), by 100%,92%,75%,17% at Week 24 (n=12), by 100%,100%,70%,30% at Week 52 (n=10), by 100%,100%,100%,83% at Week 76 (n=6), by 100%,100%,100%,80% at Week 104 (n=5) respectively. Systemic features and CRP level responded rapidly within few days, the arthritis responded later. Steady improvemaent allowed to decrease prednisolone dose inall Pts. Neutropenia was observed in 2 children during 2-3 days after infusion, but it was recovered without treatment. Growth increasing reached 5.56±2.9 cm/year (range 3-11) in Pts receiving TCZ longer than 1 year. 4 Pts had worsening of hip damage by X-ray, however at 1 patient we found X-ray improvement similar to that described by other authors (ref.1). We have also observed some unexpected effects: allergic reaction (acute urticaria during 2nd infusion in 2 Pts, Quincke’s edema during 3rd infusion - 1); non-durable sore throat on the 2nd day after infusion - 3. 3 Pts had symptoms of dramatic disease flare on 2-3 days after infusion (increasing of poliarthritis, rash, leucocytosis to 36000), state improved without treatment during 1-2 days. 2 children put the weight on (+31% and +84% added during 2 years). Conclusions TCZ therapy is able to produce physical and emotional well-being of children with sJIA even in case of a very longstanding disease. In some Pts we have observed two types of disease flare - a resolved one on the 2-3d days after infusion and/or growing one on the 15-20 days after infusion. Both of them seem to be IL6-dependent phenomenon. Collecting data on unexpected but repeated effects of TCZ therapy is important for understanding of concealed TCZ actions. References Y.Inaba et al. Ann Rheum Dis 2011; 70, 9; 1693-94. Disclosure of Interest None Declared

Objectives To present the importance of the need to remember the differential diagnosis of tumors in patients with juvenile arthritis, even in the case of a typical clinical picture of disease. Methods Presentation of clinical picture of patient who had clinically almost typically manifestations of JA, with final diagnosis – acute lymphoblastic leukemia (ALL). Results The patient, male, became ill at the age of 16.5 years. Before admission to our Institutehe was observed in a small rheumatology department at the place of residence. During this time, the clinical picture was presented subfebrile fever, complainingof pain in temporomandibulars, elbows, knees and small joints of hands and feet; skinpapular rash, considered as a manifestation of streptococcal infection. Laboratory examinations: leukopenia (3.5-2.0I10 9 ), ESR and CRP normal; blood culture “negative”. The absence of visceral lesions. MRI of wrists: marked enhancement MR signal (T2WI) from the zone of the epiphyses and metadiaphysis of all bones. The foregoing was the basis for a diagnosis: streptococcal arthritis. He received treatment with high doses of glucocorticoids (GC) (prednisone p/e 60 mg a 2; methylprednisolone pulse therapy a 3, 1 g). The patientwas hospitalized in our clinicwithillness duration of 6 months.First examinationrevealed a symmetrical polyarthritis (elbows, wrists, MCP and PIP joints of the hands, knees, ankles, MTP and IP joints ofthe feet) with the presence of contractions of elbow joints, dactylitis 2 and 3 toes, severepain on palpation of the epiphysis and diaphysis of proximal phalanges of hands, the patella, the lateral surface of the right calcaneus.There were a lot of papular rash on the face and body.Laboratory examination: Hb 139, WBC 5.9, PLT 425, ESR 4 mm/h, CRP “normal”, normalbiochemical indices,lack ofimmunological disorders (ANA, RF, ACCP, RNP). HLA B27 negative. The absence ofvisceral lesions according to the comprehensive examination, except for a small increase in the spleen up to 130×64 mm.Important in the diagnosis was to evaluate the results of MRI of hands, made earlier. Based onthese data, we suspected non-rheumatological disease, accompanied bychanges in bone marrow. In this regard, we performedMRI of knee and ankle joints, which showed the presence of foci, with increased MR signal on T2WIand decreased on T1WI. Patient were examined in a specializedoncology department; bone marrow examinationrevealed the presence of35.4% blast cells,morphologicallylymphoblasts. Set ofdata allowedto diagnose - ALL.He was directed for treatment in a specialized oncology department. Thus, a careful examination ofa number ofstudies, mostimportant of whichwas theMRI, allowed usto assumethat the changes of musculoskeletal system —manifestationof non-rheumatologicaldisease. The mostlikely explanation for thepeculiarities ofthe manifestationsof ALL, namely the absence ofchanges in the peripheralblood, is amodificationof the disease by highGCtherapy. Conclusions The presenteddata confirm the difficulty of diagnosis of JA.Rcareful study ofdata from medical history, clinical and paraclinical investigations helps to recognize the diagnosis. Used therapy can alter the manifestations of the disease. Disclosure of Interest None Declared

Methods During 3-moths cross-sectional study in 30 centers of RUS the data of 1099 consecutive patients were collected. The following key determinants of disease activity were examined: numbers of tender, swollen joints; number of active joint and joints with patient assessment of pain and global health scores (VAS); ESR; DAS 28; JADAS-71, PhGloVAS. Relationship between studied variables was investigated using of a nonparametric method of Spearman’s correlation analysis.

Methods A web-based registry collecting baseline and clinical information of autoinflammatory diseases was located at the member area of the PRINTO website (www.printo. it). Participating hospitals included pediatric rheumatology centers of the PRINTO network and adult centers with a specific interest in autoinflammatory diseases. Data was collected on Blau’s syndrome, Behcet’s disease, CAPS, CRMO, DIRA, FMF, MKD, NLRP12-mediated periodic fever, PAPA, PFAPA TRAPS and undefined periodic fevers. In total, 704 patients were included in this retrospective study on therapy.

Case report We have observed a 14-years-old female patient suffering from SLE during 4 years. She has, severe progressive nephritis with nephrotic syndrome (proteinuria 4 g/24 h), hematuria, hypoalbuminemia, high positive autoimmunity tests (ANA, anti DNA), IV class of lupus-nephritis by kidney biopsy. In the first year of disease the treatment of pulse therapy with methylprednisolone (MP) and cyclophosphamide was effective and resulted in remission of the disease. Relapse was developed after 4 years. MP Pulse therapy (6 procedures) was not successful. Rituximab therapy 375 mg/m (500 mg) was started. 2 days later the first infusion widespread papular rash without itching was appeared and persisting for 2 weeks. Then we observed febrile fever, widespread polymorphic rash (macular, papular, pustular, bullous), ESR 90 mm/hour, CRP 60 mg/l, proteinuria 3.7-4.1 g/24. Procalcitonin test was negative. Plating of pustules secretions was sterile. Skin biopsy revealed the phenomenon of hyperkeratosis, exfoliation of superficial layers of epidermis. Antibiotic and antihistamine therapy were ineffective. It was increased the dose of methylprednisolone to 1.3 mg/kg, cyclosporine A and topical skin steroids were added. Rituximab was canceled. The treatment was result in positive effects: reduction of proteinuria, hematuria and cutaneous manifestations.

Biologics are often used in therapy of DMARDs resistant JIA. The important problem is discontinuation of Biologics therapy due to different reasons.

Juvenile arthritis (JIA) is chronic potentially disabling disease, which may form certain psychological features in children

Case report A 14-year-old girl with severe JIA is under our observation. Polyarthritis involving the hips joints was formed in second year of her life. Despite for 8 years of continuous treatment by DMARDs (methotrexate, cyclosporin A, leflunomide sequentially), NSAIDs, low doses steroids (

Methods 10 children aged 4 – 12 years with anterior uveitis associated with JIA were treated by Abatacept in standard infusions pattern and doses. Indication for using Abataceptwas ineffectiveness of standard therapy of arthritis and/or uveitis. 6 patients were suffering from polyarticular variants, 4 – oligoarticular JIA. Abatacept was combined with Methotrexate in 9, Sulfasalazin in 1 and lowdose steroids in 4 children. 3 patients were switched to Abatacept from Infliximab due to non-efficacy, 7 received abatacept as a first line biologic. 9 patients had bilateral eye involvement. At the administration of Abatacept severe inflammation was seen in 1, moderate in 7, mild in 2 of the cases. Follow up period ranged from 3 to 11 month (mean 7.6). The main outcome measure was the degree of inflammation.