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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.

Text detoxification is the task of rewriting a toxic text into a neutral text while preserving its original content. It has a wide range of applications, e.g. moderation of output of neural chatbots or suggesting less emotional version of posts on social networks. This paper provides a description of RUSSE-2022 competition of detoxification methods for the Russian language. This is the first competition which features (i) parallel training data and (ii) manual evaluation. We describe the setup of the competition, the solutions of the participating teams and analyse their performance. In addition to that, the large-scale evaluation allows us to analyse the performance of automatic evaluation metrics.

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.

We tested four methods of making document representations cross-lingual for the task of semantic search for the similar papers based on the corpus of papers from three Russian conferences on NLP: Dialogue, AIST and AINL. The pipeline consisted of three stages: preprocessing, word-by-word vectorisation using models obtained with various methods to map vectors from two independent vector spaces to a common one, and search for the most similar papers based on the cosine similarity of text vectors. The four methods used can be grouped into two approaches: 1) aligning two pretrained monolingual word embedding models with a bilingual dictionary on our own (for example, with the VecMap algorithm) and 2) using pre-aligned cross-lingual word embedding models (MUSE). To find out, which approach brings more benefit to the task, we conducted a manual evaluation of the results and calculated the average precision of recommendations for all the methods mentioned above. MUSE turned out to have the highest search relevance, but the other methods produced more recommendations in a language other than the one of the target paper.

The article defines the importance of simulation modeling of traffic flows for the development of both individual territories and the entire city. The object of the study is a transport artery connecting two major districts of the city of Moscow: Strogino and Shchukino. As part of the work, the key quantitative and qualitative parameters of the object are highlighted, allowing to determine the input parameters for the simulation model of the real object in order to implement a scenario of reducing the number of lanes for personal road transport and adding a dedicated lane for public transport.

The results of formal model design of a major intersection area essential for providing residents with transport accessibility and mobility are presented in the article. Simulation methods were applied to develop a model. The quantitative and qualitative characteristics crucial for the functioning of the model as its input parameters were determined. The importance of using a model when modelling different behavior scenarios of model objects based on typical situations of the real world is established.

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783

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.

Background Biological therapy in patients with pediatric rheumatology disease may be associated with adverse events up to demyelinative lesion of CNS including multiple sclerosis (MS). It is a rare condition in the pediatric practice. Objectives to describe the clinical case of newly diagnosed psoriasis and subsequently developing of multiple sclerosis in pediatric patient revealed in JIA who has been followed-up in Pediatric department of V.A. Nasonova Research Institute of Rheumatology for 8 years. Methods Description of clinical case of 13 y.o. male Caucasian pts presented with polyarthritis variant of juvenile idiopathic arthritis (JIA) since 2006. Results The first symptoms (at the age of 1,5) were polyarthritis with fever, morning stiffness and inflammatory activity in laboratory tests in chronological link of DTP – re-vaccination. The patient admitted to the regional hospital where JIA was diagnosed and he received traditional therapy including NSAIDS, methotrexate, numerous of intraarticular injections, methylprednisolone pulse therapy with initial response. By the 2012 the child deteriorated with progressive polyarthritis, deformation of wrist joints, bilateral camptodactylia with progressive destruction on X-ray. Under the administration of abatacept therapy in our clinic in 2012 the significant improvement (70-90% ACR response) was achieved. 2 years later the plaque psoriasis developed. The cutaneous changes were impaired by the regular local application of GC so infusions of abatacept were continued. In 4th years of regular therapy (in the age of 13) sudden neurological symptoms such as headache, loss of sensitivity, ataxia, visual field defect appeared. He was admitted to neurological clinic. Multiple sclerosis was diagnosed based on the presenting signs and symptoms supporting cranial MRI – multiple focal areas of demyelination. Conclusion We presented a patient with JIA who developed two different immunological related adverse events under long-term abatacept using: psoriasis “de novo” appeared as a native origin of juvenile arthritis and CNS – multiple sclerosis. This is the first case of developing MS under the abatacept therapy among the 1118 pts (2002-2018) who receive biological therapy in our clinic. Disclosure of Interests None declared

Background Fibrodysplasia Ossificans Progressiva (FOP), also known as a “second skeleton disease” is extremely rare (1: 2000000) and disabling genetic disorder, caused by mutation of ACVR1 gene, a bone morphogenetic protein receptor. Among medical specialties there are no certain, capable to provide not only diagnostics, but also all medical maintenance (assessment and monitoring of extent of damages, the differentiated drug treatment, rehabilitation, contact with adjacent experts). It would be reasonable if the rheumatologist carried out a role of the main attending physician for the patient with FOP. It seems to be a lot of similarities between rheumatic diseases, especially spondyloarthritis (SpA) and FOP in the pathophysiology, clinical manifestation and the therapy approach. Objectives: to present the single-center experience of the FOP patients and to identify similar symptoms in FOP and rheumatic disease. Methods The analysis of the large series of patients with FOP, who observed in the rheumatologic clinic. Results Our single center experience includes 26 patients with FOP. All 26 patients (13 male and 13 female) had 3 basic FOP clinical manifestations. In 23 patients molecular-genetic tests were performed and typical mutation (Arginine 206) occurred in 22 cases and one had an extremely rare mutation (Glicine 328). 22 (85%) patients had common for FOP massive heterotopic ossifications. 3 of them had formed heterotopic ossification through the X-ray negative stage to visible changes. Among typical phenotypic stigmas were: great toe malformation; thumbs malformation; peripheral osteochondromas; cervical spine abnormalities. Majority of the cases presented some similarities to SpA manifestations: ankylosis of the apophysial joints and vertebral bodies mostly in cervical spine; X-ray/CT evidence of the sacroiliitis in all patients, who were examined (n=8). Because of severe body deformity or metal details after previous surgery intervention there were no possibility to perform MRI in most patients, but we confirm typical sacroiliitis with extended bone edema on MRI in 3 patients. Recurrent episodes of the large joints synoviitis were present in 5 patients. 4 patients demonstrated gradually formation of great toe ankylosis during the follow-up observation. The involution and decreasing of new FOP nodes associated with non-steroidal anti-inflammatory drug intake and/or glucocorticoids therapy were occurred in all patients. Conclusion Appearance of the similarities in FOP and SpA manifestation and the therapy approach could identify FOP as a potential rheumatic disease. Clinical observation of FOP patients could provide the important information for rheumatologist about insufficiently explored process of new bone formation. Disclosure of Interests None declared

Background Rare genetic pathologies involving the musculoskeletal system can be erroneously misdiagnosed as juvenile idiopathic arthritis (JIA). Idiopathic multicentric carpotarsal osteolysis (MCTO) is a congenital disease, liked to MAFB-gene mutation, described in 2012. MCTO is characterized by progressing osteolysis, mostly of carpal and tarsal bones, leading to articular deformities and functional impairment, with or without nephropathy. The incidence has not yet been established. And there is no available treatment as of today Objectives To share the experience of MCTO identification in pediatric rheumatologist practice at federal center. Methods Totally 2 MCTO cases were identified in boys 6 ad 13 years old during the period 2009 – 2018. Standard rheumatological examination was performed. Genetic testing (Sanger sequencing) in 1 patient identified MAFB-gene mutation. Results Both patients had pain and swelling in wrist and ankle joints, flexion contractures in elbow joints, and gait abnormalities. Disease duration at the time of MCTO verification was 4 and 11 years. Both patients went through erroneous polyarticular JIA diagnoses. During the follow up patients’ ESR and CRP were normal, HLA B27 - negative, ANA and RF – negative. No visceral pathology, including kidneys, was found. Therapy included NSAIDs, glucocorticosteroids – in one case, MTX and Tocilizumab gave no effect in the second patient. Radiographic findings were severe osteolysis of wrist and feet bones. JIA diagnosis was ruled out and MCTO suspected, and later confirmed in both patients by a geneticist. Heterozygous MAFB gene c.206C>T (p.Ser69Leu) mutation was detected in one patient. Conclusion Specific phenotypical features and patient’s articular status, osteolysis of the carpal and tarsal bones, absence of laboratory activity signs and of response to antirheumatic therapy is a sound motive to continue diagnostic elaboration in order not to miss rare genetically-linked conditions of the musculoskeletal system. Disclosure of Interests None declared

Background Treatment of juvenile onset rheumatic diseases (RD) is an ongoing problem because of the more aggressive disease course and more various clinical manifestations than adult-onset RD. Since the main clinical symptoms may overlap between well-known various RD, in some cases the path to diagnosis and the search for optimal therapy takes longer, especially in patients of pre-adolescence and adolescence. Objectives We described a rare case of one boy with RD who presented initially with severe dermatomyositis with sequential evolution to systemic lupus erythematosus. Methods Case report. Results A 8 yo male patient with normal physical, psychosocial and cognitive development experienced muscle weakness, periorbital erythema, Gottron symptom, dysphagia in September 2015 y, which developed after insolation. When he was admitted to hospital, increased levels of muscle-derived enzymes and positivity of ANA 1:640 were found. He was diagnosed as having juvenile dermatomyositis and was treated with prednisolone (Pr) for 3 years (IV courses repeated and per os constantly, max dose 1.5 mg/kg/day, min dose 0.5 mg/g/day), IVIG courses repeated and sequentially methotrexate, hydroxychloroquine, cyclosporine with short time of remission. Muscle weakness disappeared after the treatment, but in October 2015 y he experienced new eruptions on his face, heavy aphtosis stomatitis, lymphadenopathy, distal polyneuropathy, weight loss without strong effect after increase the dose of Pr, IVIG courses repeated, cyclosporine and added of abatacept during 6 months. Because the response to this treatment was low, etanercept was started in June 2016 y, but after two injections he had flare of disease: bright rash on the face, scalp and legs, hard aphthosis stomatitis, cheilitis, cognitive disorders, diffuse alopecia. He received IV course of Pr without significant stable effect. We reviewed diagnosis as systemic lupus erythematosus and changed therapy in November of 2016. Because he had steroid’s osteoporosis with spondylopathy, this combination that made us initiate treatment with mycophenolate mofetil and repeating courses of rituximab (3 courses in total) without increased dose of Pr. Clinical features gradually improved and now he feel goog and receive mycophenolate mofetil and Pr 5 mg/day. Conclusion This clinical observation can be considered as a course of overlap-syndrome with a successive phase change that could be triggered by anti-TNF therapy, or as an unusual course of SLE in a male patient with a predominance of myositis at onset. Treatment strategy, including of Pr, mycophenolate mofetil and rituximab in a young patient proved successful for treatment and seems to be justified in similar cases. Disclosure of Interests None declared

Background Systemic lupus erythematosus is a complex autoimmune disorder characterized by multisystem involvement, including the nervous system, which elevate damage and mortality. The investigation of neuropsychiatric involvement in childhood-onset SLE (cSLE) is important in real clinical practice to improve the prognosis. Objectives The aim of this study was to assess neuropsychiatric manifestations (NM) in cSLE in one single center. Methods The study included all pts with cSLE who undergoing in-patient treatment in our center from 1992 to 2017 yy. Diagnosis of SLE was reviewed based on 2012 SLICC criteria. Data including sex, age at the time of onset, age at the time of diagnosis, physical examination, laboratory review, and neuropsychiatric inventory were extracted from our database. Classification of NM of cSLE was according to the 1999 American College of Rheumatology (ACR) neuropsychiatric manifestations of SLE case definitions. Results We included 218 consecutive pts with cSLE, of which 45 pts (20.6%) had neuropsychiatric involvement at the time of diagnosis (Tab.1). Neurolupus was significantly more frequently detected during the acute development of SLE (46.7% of patients, p = 0.003). Among immunological disorders, patients with NM often had antibodies to RNP (p = 0.073) in the absence of any differences in other immunological parameters. Of the clinical manifestations in patients with NM, chronic skin lesions were recorded more often (p = 0.076), while arthritis was detected relatively less frequently (p = 0.028). Serositis and nephritis were diagnosed significantly more often in the group of patients with NM (p = 0.003, 0.003, respectively). Of the hematological disorders, NM was relatively more frequently accompanied by leuco/lymphopenia (p = 0.087) and thrombocytopenia (p = 0.077). In general, the group of patients with NM was characterized by a higher degree of multiorgan involvment (the number of clinical manifestations was on average 5.6 and 3.7, respectively, p As early signs of NM, all patients had mood disorders and impaired school adaptation. In the structure of NM, central nervous system involvement prevailed (89%). 15 pts (33.3%) had experienced more than one NM. Headaches, cognitive dysfunction and cerebrovascular disease were the most common (28.9%, 28.9% and 24.4%, respectively). Other NM included distal polyneuropathy - 20%, episyndrom – 15.5%, acute confusional state – 11.1%, anxiety disorder – 11.1%, psychosis – 8.9%, paresis – 6.7%, chorea – 4.4%. Conclusion Acute onset, multiorgan lesions, mood disorders, impairment of school adaptation in a patient with suspected SLE should prompt investigations into diagnosis of the primary nervous system involvement. Patients with neuropsychiatric disorders require earlier complex aggressive therapy due to greater disease activity and poor prognosis. Disclosure of Interests None declared

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.

Double-blind peer reviewing has been proved to be pretty effective and fair way of academic work selection. However, to the best of our knowledge, nobody has yet analysed the effects caused by its introduction at the Russian NLP conferences. We investigate how the double-blind peer reviewing influences gender and location (according to authors’ affiliations) biases and whether it makes two of the conferences under analysis more inclusive. The results show that gender distribution has become more equal for the Dialogue conference, but did not change for the AIST conference. The authors’ location distribution (roughly divided into ‘central’ and ‘not central’) has become more equal for AIST, but, interestingly, less equal for Dialogue.

Background To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) Methods Patients who completed the 2-year, open-label, phase III CLinical Study In Pediatric Patients of Etanercept for Treatment of ERA, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and the Juvenile Arthritis Disease Activity Score (JADAS). Efficacy data are reported as responder analyses using a hybrid method for missing data imputation and as observed cases. Safety assessments included treatment-emergent adverse events (TEAEs). Results Out of 127 patients originally enrolled in CLIPPER, 109 (86%) entered CLIPPER2. After 6 years of trial participation (2 years in CLIPPER and 4 years in CLIPPER2), 41 (32%) patients were still taking ETN, 13 (11%) entered the treatment withdrawal phase after achieving low/inactive disease (of whom 7 had to restart ETN), 36 (28%) discontinued treatment for other reasons but are still being observed, and 37 (29%) discontinued treatment permanently. According to the hybrid imputation analysis, proportions of patients achieving JIA ACR90, JIA ACR100, and JADAS inactive disease after the initial 2 years of treatment were 58%, 48%, and 32%, respectively. After the additional 4 years, those proportions in patients who remained in the trial were 46%, 35%, and 24%. Most frequently reported TEAEs [n (%), events per 100 patient-years] were headache [28 (22%), 5.3], arthralgia [24 (19%), 4.6], and pyrexia [20 (16%), 3.8]. Number and frequency of TEAEs, excluding infections and injection site reactions, decreased over the 6-year period from 193 and 173.8, respectively, during year 1 to 37 and 61.3 during year 6. A single case of malignancy (Hodgkin’s lymphoma) and no cases of active tuberculosis, demyelinating disorders, or deaths were reported. Conclusions Open-label etanercept treatment for up to 6 years was safe, well tolerated, and effective in patients with eoJIA, ERA, and PsA. Trial registration ClinicalTrials.gov: CLIPPER, NCT00962741, registered 20 August, 2009, CLIPPER2, NCT01421069, registered 22 August, 2011. Electronic supplementary material The online version of this article (10.1186/s13075-019-1916-9) contains supplementary material, which is available to authorized users.

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

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: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: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

Federal clinical recommendations were approved at the presidium meeting of the All Russian Organization “Association of ophthalmologists” 24.09.2015