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In most cases, COVID-19 has a favorable outcome. However, the risk of developing critical forms of the disease, including secondary hemophagocytic lymphohistiocytosis HLH (cytokine storm syndrome), remains high. This dictates the interest in studying pathogenetic mechanisms, features of the clinical picture, laboratory and instrumental criteria for covid-19 disease. The article analyzes the causes of acute respiratory distress syndrome and multiple organ failure as manifestations of HLH. The necessity of monitoring signs of hyperinflammation (ferritin, C-reactive protein, etc., biomarkers of inflammation) and activation of thrombosis is substantiated, in order to make timely decisions about the beginning of pathogenetic therapy. However, there are limitations for routine testing of the level of Pro-inflammatory cytokines. Information about the diagnostic criteria of HLH is summarized, and the expediency of these criteria for establishing secondary HLH, which has complicated the course of COVID-19, is emphasized.

Background New biologics developed to treat juvenile idiopathic arthritis (JIA) and the broadening range of indications for young children offer new drug switch options if the first-line treatment has proved ineffective. Nevertheless, the question regarding selection of the optimal medication depending on patients' characteristics and prior therapy still needs to be solved. Aim of the work To evaluate the efficacy and safety of adalimumab (ADA) as the first and subsequent biologic drug in children under 4 years of age. Patients and methods Analysis was performed using the Research Center for Children’s Health registry data, including the prospective observational results involving children with JIA who had started ADA treatment between 2009 and 2012. Patients were allocated into the biologic-switcher (n = 8) and biologic-naive (n = 17) groups according to prior treatment. The response to therapy was assessed using the ACR Pedi and the modified Wallace criteria. Results The percentage of patients who had achieved ACR50/70/90 after 24-month therapy was 82.4/76.5/64.7% in the biologic-naive and 62.5/50.0/37.5% in the biologic-switcher group. The percentages of patients who had achieved remission were comparable between the two groups (41.2 and 37.5%, respectively). 23 AEs occurred in 16 (64%) patients throughout the follow-up period. ADA was withdrawn from 6(24%) patients. One (5.9%) biologic-naive patient and 2(25%) biologic-switchers discontinued treatment because of lack of efficacy. Conclusions ADA is efficacious and relatively safe in children younger than 4 years. However, ADA showed better efficacy in achieving ACR70/90 and maintaining the lowest disease activity at 24 months treatment in biologic-naive patients.

Evaluation of the safety profile of vaccines in patients with rheumatic diseases requires an assessment of their impact on disease activity. The effect of antipneumococcal vaccination on the activity of systemic juvenile idiopathic arthritis (sJIA) has not been studied so far. Objective. To evaluate the dynamics of sJIA activity after immunization with pneumococcal 13-valent conjugate vaccine (PCV13) of patients receiving biologicals. Patients and methods. This study included patients with sJIA in remission or active disease receiving biologicals during inpatient treatment and vaccinated with PCV13. To evaluate the effect of immunization on sJIA activity, we measured serum levels of high-sensitivity C-reactive protein (hs-CRP) and calprotectin. In addition to that, we assessed the number of new cases, when concentration of these markers was above the upper limit (UL) 4 weeks after PCV13 administration. Results. In 18 out of 53 patients in remission (34%) and 3 out of 25 patients with active sJIA (12%), hs-CRP levels were undetectable (0.1 mg/L) at both time-points (baseline and after 4 weeks). Among those with detectable hs-CRP levels in at least one time-point 4 weeks after vaccination, patients in remission (n = 35) had no significant changes in hs-CRP (median -0.17 mg/mL; 95% CI -0.84…0.41), whereas patients with active sJIA (n = 22) demonstrated a 3-fold decrease in hs-CRP level (median -0.94 mg/mL (95% CI -3.93…0.05). We observed no significant difference in calprotectin levels in the groups. Concentration of hs-CRP above the UL 4 weeks after vaccination was detected in 2 out of 53 sJIA patients in remission (4%) and none of the patients with active sJIA. Сoncentration of calprotectin above the UL 4 weeks after vaccination was detected in 8 out 53 (15%) and 5 out 25 (20%) sJIA patients in remission and with active disease, respectively. Conclusion. Vaccination against pneumococcal infection in patients with sJIA led to an increase in the level of highly sensitive laboratory markers of sJIA activity in 4–20% of patients. Key words: disease activity, safety, high-sensitivity C-reactive protein, biological drugs, calprotectin, juvenile idiopathic arthritis, pneumococcal 13-valent conjugate vaccine

Background: Both the steroid- and NSAID-sparing effects of biologics in juvenile idiopathic arthritis (JIA) treatment are key aspects of the dynamics of patient’s condition. The proper selection of biologics enables maximum treatment effectiveness and reduction of the dosage of concomitant therapy. Our aim was to study the dynamics of concomitant therapy during etanercept (ETA) and methotrexate (MTX) treatment in patients with JIA. Methods: This analysis included 215 JIA patients (63.3% females) showing sufficient response to main therapy. One hundred patients received MTX as main therapy, 24 received ETA monotherapy, and 91 received ETA þ MTX combination therapy. The dynamics of concomitant therapy were analyzed after 1 month, every 3 months during the first year, and every 6 months during the long-term follow-up (up to 5 years). Results: At the baseline, 24 (11.2%) patients received concomitant oral glucocorticoids (orGCs) and NSAIDs; the remaining 191 (88.8%) patients were treated with concomitant NSAIDs only. Within 1-year treatment, NSAIDs were discontinued in 162 (75.3%) patients. There were no significant differences in the dynamics of withdrawal of NSAIDs in patients who received and did not receive concomitant MTX. However, the percentage of treatment discontinuation in the MTX group was significantly lower compared to the other two groups (p < 0.001). Oral GCs were discontinued completely in 4 children (16.7%), and the dose of oral GCs was reduced in another 4 patients (16.7%). By the end of the follow-up period, 44 of 115 patients (38.3%) treated with ETA in combination with any concomitant therapy could switch to ETA monotherapy. Conclusion: Therapy with ETA makes it possible to reduce the dosage or completely discontinue most concomitant medications (orGCs, NSAIDs, MTX) in a significant percentage of patients. This reduces the risk of development of NSAID- and GC-induced pathological conditions, while the effectiveness of therapy of the underlying condition remains high. Key Words: concomitant treatment, etanercept, juvenile idiopathic arthritis, NSAID

Introduction: In 2011, Etanercept (ETA) was approved for clinical application in patients with Juvenile Idiopathic Arthritis (JIA) older than 2 years of age; Adalimumab (ADA) was approved in 2013. However, the available data for these patients are not sufficient even in large-scale registers. In older children, uveitis is a factor taken into consideration when choosing anti-TNF therapy, so we believe that its onset at an early age may affect the efficacy of treatment with different anti-TNF drugs. Objectives: This study aimed to evaluate the comparative efficacy of ADA and ETA in children of young age depending on their uveitis status. Methods: Comparative analysis involved patients who had initiated ETA (n=49, no active uveitis) or ADA (n=25; 13 patients with active uveitis and 12 patients without uveitis) therapy at an age of ≤4 years. Treatment efficacy was evaluated according to the dynamics of clinical signs and laboratory values, the ACRPedi and Wallace criteria. Results: ETA and ADA proved very efficacious in children under 4 years of age already after the first month of therapy according to the disease activity scores, laboratory values, and morning stiffness duration. After 3 months of therapy, the number of affected joints was substantially reduced in all three groups (pp-values are insignificant). Conclusion: In children younger than 4 years, ADA shows higher efficacy in patients with uveitis as compared to those without uveitis. Children without uveitis show a better response to ETA, although there is a risk of de novo uveitis. Therefore, ADA is the drug of choice for children with uveitis under 4 years of age, while ETA is preferred in children without uveitis.

Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the ...

BackgroundSystemic lupus erythematosus (SLE) is characterized by multiple autoantibodies associated with a multisystem illness where any organ can be targeted. There are different classification criteria for SLE. Sensitivity and specificity of three criteria have been debated and may vary in different populations and clinical settings.ObjectivesWe aim to evaluate the clinical and laboratory symptoms of the onset of systemic lupus erythematosus in pediatric population.MethodsA total of 116 SLE patients (female –92, male-24) were included into the study. We analyzed the primary diagnosis, the time before identification the SLE, clinical and laboratory symptoms, their combination, and fulfilling the classification criteria of SLE. All data is presented as Me (IQR).ResultsThe age of the onset of SLE was 13.3 (10.7, 15.2) years. 55/116 patients had other diagnosis before the verification of SLE, the time before the verification was 10 (5, 26) months. The loss of weigh was in 63(54%) of patients, fever – in 83(72%) (febrile – 57, subfebrile -26), adenopathy in 55(47%), malar rash – in 45(39%), discoid rash – in 19(16%), alopecia – in 19 (16%), photosensitivity – in 39(34%), oral ulcers – in 38 (33%), nazal ulcers – in 11(9.5%), arthritis – in 31(27%), pleuritis- in 18(16%), pericarditis- in 20(17%), renal disorder – in 52(47%), seizures- in 7(6%), psychosis – in 1(0.9%), myelitis – in 2(1.7%), peripheral neuropathy – in 3(2.6%), cranial neuropathy – in 2(1.7%), hemolytic anemia – in 59(51%), leukopenia- in 62(53%), thrombocytopenia- in 27(23%), ANA positivity – in 100(86%), anti-dsDNA antibody positivity – in 91(78%), antiphospholipid antibody positivity– in 27 (25%), direct Coombs’ test- in 22(19%). SELENA–SLEDAI Score was 13 (9, 20): low activity- in 14(12%) patients, moderate activity- in 23(20%), high activity – in 42(36%), very high activity – in 37(32%).96 (83%) patients met the eligibility criteria ELAR/ACR 2019, 112(97%) – ACR criteria modified in 1997, 106(91%) – SLICC in 2012.ConclusionIn this cohort, although all three criteria have sufficient. Some SLE patients with a clinical diagnosis lacked sufficient number of criteria.Disclosure of InterestsRina Denisova Speakers bureau: Speaker for Roche, AbbVie, MSD, Novartis., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Sanofi and Novartis., Ekaterina Alexeeva Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., Tatyana Dvoryakovskaya Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly,AbbVie, Bristol-Myers Squibb, MSD, Amgen and Novartis., Ksenia Isaeva Grant/research support from: Financial grants from Roche, Novartis and Sanofi., Aleksandra Chomakhidze: None declared, Anna Mamutova Speakers bureau: Speaker for Novartis., Grant/research support from: Financial grants from Eli Lilly., Olga Lomakina Grant/research support from: Financial grants from Pfizer, Eli Lilly., Anna Fetisova Grant/research support from: Financial grants from Amgen., Marina Gautier: None declared, Kristina Chibisova: None declared, Ivan Kriulin Speakers bureau: Speaker for Novartis., Elizaveta Krekhova Speakers bureau: Speaker for Novartis., Irina Tsulukiya: None declared

BackgroundUveitis is the most common extra-articular manifestation of JIA which may lead to sight-threatening ocular complications. Topical corticosteroids are still used in the initial treatment for JIA-associated uveitis. The goal of treatment in these patients should be topical corticosteroid-free remission and prevention of recurrences. The most commonly used corticosteroid-sparing immunomodulatory are TNF-α inhibitors (TNFi), especially adalimumab.Currently, limited data are available about when or how to stop adalimumab when remission of JIA-associated uveitis is presumed.ObjectivesTo evaluate rates of relapse after discontinuation adalimumab in patients with JIA-associated uveitis.MethodsMedical records of 33 patients with JIA-associated uveitis who were successfully treated with adalimumab to a state of topical corticosteroid-free remission and discontinued adalimumab due to a long-term remission were analyzed retrospectively.Remission of uveitis was defined as ResultsCorticosteroid-sparing control of inflammation was achieved in all patients. Adalimumab was discontinued after 50 (range 12–120) months after initiation of adalimumab. Duration of remission prior to discontinuing adalimumab was 42 (range 6 – 114) months. The mean duration of remission after adalimumab discontinuation was 14 (range 1–59) months. 13 (40%) of patients had flares after less than 12 months after discontinuing adalimumab, 5 (15%) had flares after 12 – 24 months, 15 (45%) had not flared due to 24 months after discontinuation adalimumab and had had a long-term non-biological remission. Disease was successfully controlled in 11(33%) patients with non-biological DMARDs, 22 (66%) patients restarted biological therapy after flares, due to lack of improvement after non-biological DMARDs. All patients in whom biological therapy was reinitiated responded satisfactorily. None of the flared patients didn’t require restarting corticosteroids.ConclusionCorticosteroid-sparing control of inflammation was achieved in all patients. Data from our experience with adalimumab in patients with JIA-associated uveitis suggest that 45 % of patients can be successfully withdrawn from biologics for at least 24 months without disease recurrence.References[1]Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of uveitis nomenclature for reporting clinical data: results of the First International Workshop. Am J Ophthalmol 2005;140: 509-16.Disclosure of InterestsIrina Tsulukiya: None declared, Ekaterina Alexeeva Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., Tatyana Dvoryakovskaya Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis., Rina Denisova Speakers bureau: Speaker for Roche, AbbVie, MSD, Novartis., Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Sanofi and Novartis., Anna Mamutova Speakers bureau: Speaker for Novartis., Grant/research support from: Financial grants from Eli Lilly., Ksenia Isaeva Grant/research support from: Financial grants from Roche, Novartis and Sanofi., Aleksandra Chomakhidze: None declared, Olga Lomakina Grant/research support from: Financial grants from Pfizer, Eli Lilly., Anna Fetisova Grant/research support from: Financial grants from Amgen., Marina Gautier: None declared, Kristina Chibisova: None declared, Ivan Kriulin Speakers bureau: Speaker for Novartis., Elizaveta Krekhova Speakers bureau: Speaker for Novartis., Maria Botova: None declared

BackgroundSystemic juvenile idiopathic arthritis (sJIA) is the rarest variant of juvenile idiopathic arthritis, characterized by severe course, frequent exacerbations, the development of life-threatening extra-articular manifestations and complications, which requires the use of expensive medications and frequent hospitalizations of patients. In the Russian Federation, the provision of medicines to patients with sJIA is carried out at the expense of the federal budget, in this regard, the Federal Register of sJIA was created in 2018.ObjectivesTo analyze biologic therapy in patients with sJIA according to the data of the Federal Register of the Russian Federation.MethodsRetrospective analysis of epicrisis of patients receiving biologic therapy with a diagnosis of sJIA included in the Federal Register of the Russian Federation. The analysis included patients receiving the following drugs of biologic therapy: tocilizumab, сanakinumab, etanercept, adalimumab.ResultsIn 2018, 582 patients receiving biologic therapy were included in the Federal Register. Since 2019, the number of patients has steadily increased: in 2019 there were 796, in 2020 - 949, in 2021 - 1041 patients.The Federal Register of the Russian Federation includes patients under the age of 18 (in 2018 – 471, in 2019 – 666, in 2020 – 806, in 2021 – 790 patients) and patients over the age of 18 (in 2018 – 111, in 2019 – 130, in 2020 – 143, in 2021 – 250 patients).During the four-year follow-up, patients receiving tocilizumab predominate - on average 72.25% (in 2018 – 74%, in 2019 – 73.1%, in 2020 – 70.3%, in 2021 – 71.6% of patients).Therapy with using of TNF-α inhibitors remains without statistically significant dynamics: in 2018 – 38 (6.5%) received etanercept, in 2019 – 42 (5.3%), in 2020 – 44 (4.6%), in 2021 – 46 (4.4%); in 2018 – 22 (3.8%) received adalimumab, in 2019 – 25 (3.1%), in 2020 – 27 (2.9%), in 2021 – 29 (2.8%) patients.The number of patients receiving сanakinumab has more than doubled since 2018 (in 2018 – 91 (15%), in 2019 – 147 (18.5%), in 2020 – 210 (22.3%), in 2021 - 220 (21.1%) patients.ConclusionThe number of patients receiving biologic therapy with sJIA in the Russian Federation has increased, which is due to the natural growth of the disease and more affordable provision of patients with sJIA by the state.References[1]Lee JJY, Schneider R. Systemic Juvenile Idiopathic Arthritis. Pediatr Clin North Am. 2018 Aug;65(4):691-709. doi: 10.1016/j.pcl.2018.04.005. PMID: 30031494.Disclosure of InterestsMaria Botova: None declared, Ekaterina Alexeeva Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer.,, Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis.,, Tatyana Dvoryakovskaya Speakers bureau: Speaker for Roche, AbbVie, Bristol-Myers, Squibb, MSD, Novartis and Pfizer.,, Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Eli Lilly, AbbVie, Bristol-Myers Squibb, MSD, Sanofi, Amgen and Novartis.,, Rina Denisova Speakers bureau: Speaker for Roche, AbbVie, MSD, Novartis.,, Grant/research support from: Financial grants from Roche, Pfizer, Centocor, Sanofi and Novartis.,, Anna Mamutova Speakers bureau: Speaker for Novartis.,, Grant/research support from: Financial grants from Eli Lilly.,, Ksenia Isaeva Grant/research support from: Financial grants from Roche, Novartis and Sanofi.,, Aleksandra Chomakhidze: None declared, Olga Lomakina Grant/research support from: Financial grants from Pfizer, Eli Lilly.,, Anna Fetisova Grant/research support from: Financial grants from Amgen.,, Marina Gautier: None declared, Kristina Chibisova: None declared, Elizaveta Krekhova Speakers bureau: Speaker for Novartis.,, Ivan Kriulin Speakers bureau: Speaker for Novartis.,, Irina Tsulukiya: None declared, Tatyana Kriulina: None declared, Natalya Kondratyeva: None declared

Background:The efficacy of tocilizumab for treatment patients with systemic juvenile idiopathic arthritis (sJIA) was demonstrated before. We want to describe tocilizumab drug survival based on data from a single-center observation.Objectives:To analyze the drug survival of tocilizumab in patients with sJIA treated at the National Medical Research Center of Children`s health, Moscow, Russia.Methods:Medical records from sJIA patients treated with tocilizumab (TOC) were analyzed retrospectively from the National Medical Research Center of Children`s health, Moscow, Russia.Results:One hundred ninety-two patients presenting with sJIA were included in this observation, with a median age at treatment initiation of 7,2 (interquartile range, IQR 3,9-10,8) years and a median disease duration of 1,9 (IQR 0,4-5,9) years. All patients had been bio-naive. TOC therapy was highly effective in patients with sJIA. At 6 month of follow-up 148/172 (86%) patients achieved inactive disease according the criteria C. Wallace, disease activity persisted in 24/172 (14%) patients. At 1 year of medication 139/150 (92%) patients had inactive disease. We analyzed the reason of TOC withdrawal retrospectively. A total of 82/192 drug withdrawals were performed. TOC was discontinued due to primary ineffectiveness in 4 patients, due to secondary ineffectiveness in 39 patients. 33 patients achieved drug-free remission. Six patients developed side effects that required discontinuation of TOC therapy (4 patients had allergic reactions, 1 patient developed tuberculosis, 1 patient had severe neutropenia). 47/82 patients were switched on other biologic drug: on canakinumab (31), on TNF-inhibitors (11), on rituximab (5). In summary, TOC was canceled in 49/192 (25%) patients due to ineffectiveness or AEs in our cohort.Conclusion:These results demonstrated that TOC is highly effective as the first biologic drug in patients with sJIA. Our observations have shown a good tolerability and survival of the IL-6 inhibitor TOC in patients with sJIA treated in a real-world clinical setting.Disclosure of Interests:None declared

Made available in DSpace on 2021-06-25T10:38:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 Healthway Objective. To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. Methods. The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. Results. A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. Conclusion. The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively. UOC Clinica Pediatrica e Reumatologia IRCCS Istituto Giannina Gaslini Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno-Infantili (DiNOGMI) Università degli Studi di Genova Dipartimento di Epidemiologia e Biostatistica IRCCS Istituto Giannina Gaslini Faculty of Medicine Ain Shams University Pediatric Rheumatology Division Institute of Child Health Section of Pediatric Rheumatology SRCC Children's Hospital Rheumatology Division Pediatric Department Faculty of Medicine Ramathibodi Hospital Mahidol University Pediatric Rheumatology Clinic R G Kar Medical College Division of Rheumatology IRCCS Ospedale Pediatrico Bambino Gesù Division of Pediatric Rheumatology Institute of Child Health Sir Ganga Ram Hospital Faculty of Medicine Benha University Faculty of Medicine Alexandria University Faculty of Medicine Tanta University Faculty of Medicine Cairo University Pediatric Rheumatology Division Adolescent Health Care Unit Universidade do Estado do Rio de Janeiro Department of Internal Medicine Universidade Federal do Rio de Janeiro Servicio de Inmunología y Reumatología Hospital de Pediatría Garrahan Department of Clinical Sciences and Community Health University of Milan Division of Rheumatology University Hospital Meyer Rheumatology Division National Medical Research Center of Children's Health Sechenov First Moscow State Medical University Department of Immunology Rheumatology and Allergy Queen Rania Children's Hospital Saint-Petersburg State Pediatric Medical University UOC Pediatria a Media Intensità di Cure Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Rheumatology Department Faculty of Medicine Suez Canal University Department of Pediatrics King Faisal Specialist Hospital and Research Center Dipartimento Promise G. D'Alessandro Università degli Studi di Palermo Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP UOC Pediatria Servizio di Immuno-Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Messina UO Nefrologia e Reumatologia Pediatrica Azienda Ospedaliera Universitaria Gaetano Martino Department of Pediatrics School of Medicine Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Pediatric Unit Ospedale Vito Fazzi Pediatric Unit AON SS Antonio e Biagio e Cesare Arrigo Children's Hospital Pediatric Department Hospital das Clínicas Botucatu Medicine University UNESP

Objectives To assess the influence of the genetically engineered biologic drug etanercept on the quality of life of patients with juvenile idiopathic arthritis (JIA). Methods The research included 85 children with poly-and oligoarticular variant of the JIA at the age of 5 (2; 17) years. The assessment of the quality of life of patients was carried out by means of the parental version of a special questionnaire CHAQ (Childhood Health Assessment Questionnaire), Health Utilities Index Mark 3 (HUI3) questionnaire. The doctor and parents of the patient also assessed the global activity of the illness by the 100-mm visual analog scale (VAS) before the etanercept prescription and in 1, 6 and 12 months. All patients before the etanercept prescription received immunosuppressive agents. Results Impressive increase in an average point of the quality of life (the response in 1 month after the therapy beginning) was noted by the attributes of a questionnaire of HUI3 «emotions» — from 0.82 (± 0.18) to 0.90 (± 0.13), p =0.001, «cognitive abilities» — from 0.85 (± 0.17) to 0.91 (± 0.18), p =0.006, and «pain» — from 0.78 (± 0.23) to 0.91 (± 0.1), p Conclusions Treatment with the etanercept provided the improvement of the quality of life of children with the JIA and their families, improvement of physical activity and emotional state of patients.

Background Macrophage activation syndrome (MAS) is a rare and severe complication of juvenile idiopathic arthritis (JIA) that most typically develops in patients with its systemic form (sJIA). Tocilizumab proved to be efficacious for treatment of both systemic JIA and polyarthritis. Nevertheless, the question regarding the effect of MAS on efficacy of TOC therapy in patients with sJIA is still to be solved. Objectives To evaluate the efficacy of tocilizumab therapy in patients having sJIA and MAS versus the patients without MAS. Methods Throughout the period between 2009 and 2018, 251 children with the acute phase of sJIA started to be treated with TOC at the Rheumatology Department of the National Medical Research Center of Children’s Health (Moscow, Russia). Of those, 69 patients had active MAS at initiation of TOC therapy. Patients were diagnosed with MAS according to the preliminary diagnostic guidelines for MAS complicating sJIA [1]. Treatment efficacy was evaluated according to the dynamics of clinical and laboratory signs using the ACRPedi criteria. The Wallace criteria were used to evaluate whether or not remission had been achieved. Results At initiation of TOC therapy, patients with and without MAS were comparable in terms of their sex and age characteristics, as well as the overall severity of arthritis (the percentage of women, 56.6% (intergroup p=0.396); the median age, 7.83 (4.39-11.3) years (intergroup p=0.640); and JADAS-71, 17.4 (13.7-22.8) (intergroup p=0.055)). Nevertheless, patients differed in terms of intensity of certain clinical manifestations and prior history of the disease. The group with MAS was characterized by such parameters as shorter disease duration, shorter duration morning stiffness, and smaller number of affected joints but higher activity and severity score (Patient/Parent and Physician VAS score). After treatment initiation, TOC was discontinued after treatment for 4-12 weeks only in 2 out of 69 (2.9%) patients because of persistent MAS or MAS flare. The patients successfully achieved remission after therapy switching. No intergroup differences were observed for the rate of treatment discontinuation within the first year of therapy: the drug was discontinued in 5 (7.2%) patients in the MAS+sJIA group (2 MAS flares + 3 cases of poor efficacy) and in 25 (13.7%) patients in the sJIA group (4 SAEs + 21 cases of poor efficacy). One-year treatment with TOC proved that this drug is highly efficacious to treat sJIA regardless of whether or not patients had MAS at treatment initiation (Figure). No deaths were reported throughout the entire treatment period. We attributed this to early diagnosis and high efficacy of treatment of JIA patients. Conclusion Tocilizumab therapy in patients with sJIA in the presence of MAS is as efficacious as in patients without MAS and does not aggravate the course of MAS. Reference [1] Ravelli A, Magni-Manzoni S, Pistorio A, Besana C, Foti T, Ruperto N, Viola S, Martini A. Preliminary diagnostic guidelines for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2005;146(5):598-604. Disclosure of Interests None declared

Background Development of biologics and their launching into clinical practice has yielded significant progress in pediatric rheumatology. Nevertheless, treatment of severe disorders, and systemic JIA in particular, still remains a challenge. JIA often has the early-onset form. If its course is aggressive and persistent, patients exhibit poor response to treatment with first-line biologics. Effectiveness of the second-line and subsequent biologics, as well as the optimal sequence of prescribing drugs belonging to different classes to children younger than 4 years, remains an open question Objectives To compare the efficacy of canakinumab (CAN) in children with sJIA younger than 4 years (in biologic-naive patients and when prescribed as a second-line biologic). Methods The study was conducted as a subanalysis of the prospective cohort study to evaluate the efficacy of biologics in children with sJIA. Comparative analysis involved 17 patients who had initiated CAN treatment at the National Medical Research Center of Children’s Health (Moscow, Russia) when aged Results At baseline, patients had comparable duration and severity of the disease. The biologic proved efficacious already after 4 weeks of treatment. Five (55.6%) patients in the naive group and 4 (50%) patients in the switched group achieved ACR90 (p>0.999) within one year of treatment. A state of inactive disease according to the Wallace criteria was achieved in one patient in each group, (12.5% and 11.1%, respectively (p>0.999). JADAS-71 decreased significantly from 12.8 (IQR 10.4-16.2) to 4.4 (IQR 2-6.8) in the naive group (p=0.012) and from 11.6 (IQR 8-13.88) to 2.35 (IQR 1-3.03) in the switched group (p=0.017). Conclusion CAN was found to be highly efficacious and have a good safety profile in children younger than 4 years regardless of prior biologic treatment. Disclosure of Interests None declared

Background:Familial Mediterranean fever (FMF) is a monogenic autoinflammatory hereditary disease characterized by recurrent episodes of fever with sterile peritonitis, pleural inflammation, arthritis, and/or erysipelas-like rash. Among all variants of the MEFV gene, according to the literature, five pathogenic ones have been identified, which in 75% of cases lead to the development of a typical clinical presentation: V726A, M694V, M694I, M680I, and E148Q. Among them, the M694V variant is the most common and occurs in patients with FMF in 20-65% of cases. At the same time, approximately 10 to 20% of patients meeting the diagnostic criteria for FMF do not have pathogenic variants in the MEFV gene. Despite the fact that the molecular genetic, pathogenetic and clinical features of the disease have been studied detailed, the diagnosis remains difficult due to the lack of a clear correlation between the patient’s clinical and genetic data.Objectives:To analyze the obtained genetic data of patients with pathogenic variants in the MEFV gene.Methods:The study included 103 patients who are mainly observed at the rheumatology department of the National Medical Research Center of Children’s Health of Ministry of Health of the Russian Federation in Moscow. All patients underwent analysis of the MEFV gene using Sanger sequencing with further statistical processing of the data obtained.Results:Of 103 patients, the pathogenic variant of the MEFV gene was found in 93 patients (90.3%), in 10 patients (9.7%) - the pathogenicity of the revealed variant was contradictory. Of 93 patients with the pathogenic variant of MEFV, the clinical presentation of the disease fits to FMF in 37 patients (39.6%). 11 (29.7%) of them had a mutation in M694V. Out of 37 children who met the criteria for FMF diagnosis, 15 (40.5%) children had a homozygous pathogenic variant of MEVF, and 22 (59.5%) children had two mutations in a heterozygous state. 57 patients who do not have a typical clinical presentation, which is specifical for FMF are observed at the departments of rheumatology, cardiology and nephrology, 13 patients are on an outpatient observation, and 6 patients at the time of the study are over 18 years old. 8 (14%) of them had a mutation in M694V. Among 57 patients with pathogenic heterozygous variants in a, 22 patients (38.6%) are observed in the rheumatology department, among them:• Enthesitis-related arthritis - 2 patients (9%);• Systemic juvenile arthritis - 13 patients (59%);• Oligoarthritis - 5 patients (23%);• Polyarthritis- 2 patients (9%).Conclusion:Analysis of the obtained data showed that FMF is characterized by a combination of the clinical presentation and the pathogenic variant in the MEFV gene. However, the disease manifests itself not only in the homozygous pathogenic variant, but also in the combination of two mutations in heterozygous. The presence of one heterozygous mutation, generally, does not lead to the development of FMF.References:[1]Konstantopoulos, A. Kanta, C. Deltas, V. Atamian, D. Mavrogianni, A.G. Tzioufas, I. Kollainis, K. Ritis, H.M. Moutsopoulos, Familial Mediterranean fever associated pyrin mutations in Greece Ann. Rheum. Dis., 62 (2003), pp. 479-481, 10.1136/ard.62.5.479.[2]Gershoni-Baruch R, Brik R, Zacks N, Shinawi M, Lidar M, Livneh A: The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with Mediterranean Fever,Seminars in Arthritis and Rheumatism,Volume 43, Issue 3, 2013, Pages 387-391familial Mediterranean fever. Arthritis Rheum 2003; 48: 1149–1155.[3]Booty MG, Chae JJ, Masters SL, et al. Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 2009; 60:185.Disclosure of Interests:None declared

Background:Macrophage activation syndrome (MAS) is a life-threatening complication of systemic-onset juvenile idiopathic arthritis (sJIA) characterized by fever, hepatosplenomegaly, lymphadenopathy, coagulopathy, and rapid development of multiple organ failure. MAS is triggered by viral and bacterial infections, most often Epstein-Barr viruses, cytomegalovirus, influenza and parainfluenza viruses, parvavirus B19, yersiniosis, salmonellosis, sepsis.Despite modern diagnostic and treatment technologies, MAS still remains a formidable complication of sJIA, it is characterized by an aggressive course, a heterogeneous clinical presentation, especially in conditions of treatment with genetically engineered biological drugs, an ambiguous response to pathogenetic therapy and is accompanied by mortality in 5-10% of patients.Objectives:To analyze the clinical and laboratory features of MAS in children with sJIA and to study the genetic predisposition of this syndrome.Methods:The study included 24 patients with MAS who are being followed up in the rheumatology department of the National Medical Research Center of Children’s Health, Moscow. The clinical presentation and laboratory manifestations were assessed in 24, and genetic features were described in 7 patients using a new generation sequencing with further biostatistical processing of the obtained genetic data.Results:Of 24 patients, 23 (98%) had fever, 16 (68%) patients had rash, 17 (72%) - organomegaly, 4 (16%) - polyserositis, 2 (7%) - myalgia and myopathy. All 24 (100%) patients had an increase in ferritin level of more than 684 ng/ml, 98% of them had a high level of lactate dehydrogenase (LDH) and 97% - a high level of triglycerides. In CBC, cytopenia was found in 80% of children: in 54% - erythrocytopenia, in 74% - leukopenia, in 88% - thrombocytopenia, in 15% - sharp decrease in erythrocyte sedimentation rate. In a coagulogram of 24 patients, 90% had an increase in D-dimer, 85% had a decrease in fibrinogen. Hyponatremia presented in 95% of patients. Thus, 85% of patients met the diagnostic criteria of the HLH-2004 protocol, adapted for children with sJIA. Genetic characteristics were analyzed in 7 children out of 94 patients with MAS. They are presented in Table 1. These patients have rare and frequent variants, as well as genes polymorphisms that are associated with macrophage activation syndrome.Table 1.The number of genetic variants in children with MAS (n=7).GenePatient № 1Patient №2Patient № 3Patient № 4Patient №5Patient №6Patient №7LYST02473464NLRC44444463NLRP12510644124NLRP31855575TNFAIP32220222UNC13D182510182618XIAP1100131Conclusion:The macrophage activation syndrome has a typical clinical presentation, there are clinical and laboratory manifestations: fever, hyperferritinemia, cytopenia, hyponatremia, increased levels of LDH and triglycerides, based on which, a diagnosis can be made. Patients with MAS at our center also had genetic characteristics that predisposed to the development of this condition.References:[1]Crayne CB, Albeituni S, Nichols KE, Cron RQ. The Immunology of Macrophage Activation Syndrome. Front Immunol. 2019 Feb 1;10:119. doi: 10.3389/fimmu.2019.00119. PMID: 30774631; PMCID: PMC6367262.[2]Henderson LA, Cron RQ. Macrophage Activation Syndrome and Secondary Hemophagocytic Lymphohistiocytosis in Childhood Inflammatory Disorders: Diagnosis and Management. Paediatr Drugs. 2020 Feb;22(1):29-44. doi: 10.1007/s40272-019-00367-1. PMID: 31732958; PMCID: PMC7334831.[3]Ravelli A, Davì S, Minoia F, Martini A, Cron RQ. Macrophage Activation Syndrome. Hematol Oncol Clin North Am. 2015 Oct;29(5):927-41. doi: 10.1016/j.hoc.2015.06.010. Epub 2015 Aug 25. PMID: 26461152.Disclosure of Interests:None declared

Background:The safety of vaccination of children with rheumatic diseases is determined not only by the risk of adverse events but also by the risk of exacerbation of the disease. The simultaneous administration of several vaccines can increase the likelihood of these events.Objectives:To evaluate the clinical and laboratory signs of disease activity in children with juvenile idiopathic arthritis (JIA) after simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) infections.Methods:We included hospitalized patients with JIA ages 2 through 18 without serious comorbidity, immunized with polysaccharide conjugate vaccines against pneumococcal (PCV13) and Hib infections. Vaccines were administered (0.5 ml each) concurrently subcutaneously into the deltoid area. In all children before and 3 weeks after vaccination, clinical (joints with active arthritis, uveitis activity) and laboratory signs (increased ESR, concentrations of highly sensitive C-reactive protein – hsCRP, and calprotectin) of JIA activity were assessed. Serum hsCRP and calprotectin were quantified by ELISA. The upper limit of the reference interval for hsCRP was considered (according to the manufacturer’s instructions) a value of 8.2 mg/L, for calprotectin – 2.9 μg/ml, and for ESR – > 10 mm/h.Results:The study included 430 patients with JIA (girls 60.9%), median (IQR) age – 11.1 years (7.3 to 14.4), onset of JIA – 4.7 years (2.4 to 8.6). Patients with persistent oligoarticular JIA numbered 149 (34.7%), polyarticular RF-negative – 148 (34.4%), systemic – 101 (23.4%), enthesitis-related – 20 (4.7%), and polyarticular RF-positive JIA – 12 (2.8%). Biologic disease-modifying antirheumatic drugs (DMARDs) were administered to 278 (64.7%), non-biologic DMARDs (mostly methotrexate) – 282 (65.6%), corticosteroids – 45 (10.5%), and NSAIDs – 18 (4.2%) patients. Three weeks after vaccination, out of 100 (23.3%) patients with initially active joints, signs of active arthritis remained in 96 patients, of which 16 patients had a decrease in the median (IQR) number of active joints by 4 (2 to 8). Among patients without active joints at baseline, signs of active arthritis were not subsequently detected. Before vaccination, 9 patients had uveitis in the exacerbation phase, 7 - in the subactive phase, and 41 - in the remission phase. After vaccination, exacerbation of uveitis persisted in 4 patients. There were no new cases of uveitis or its exacerbation. The dynamics of laboratory signs of JIA activity are presented in Table 1. Initially, the high concentration of calprotectin was found in 191 (44.4%) patients, and after vaccination – in 220 (51.2%) patients; the difference was 6.7% (95% CI 1.0 - 12.5); hsCRP - in 34 (7.9%) and 51 (11.9%) patients; the difference was 4.0% (95% CI 0.6 - 7.3); high ESR – in 76 (17.7%) and 41 (9.5%) patients; the difference was -8.1% (95% CI -11.6 to -4.7), respectively. An independent predictor of new cases of high concentration of hsCRP (n = 36), but not new cases of high concentration of calprotectin (n = 94), was the initial number of joints with active arthritis – odds ratio 2.37 (95% CI 1.14 - 4.93).Table 1.Laboratory signs of JIA activity after simultaneous administration of vaccines against pneumococcal (PCV13) and Hib-infectionsVariablesBaselineAfter 3 weeksRatio*p**Geometric mean (95% CI)Calprotectin, μg/ml2.93 (2.70 – 3.17)3.15 (2.92 – 3.40)1.08 (0.99 – 1.17)0.087hsCRP, mg/L0.69 (0.60 – 0.78)0.79 (0.69 – 0.90)1.15 (0.99 – 1.33)0.073ESR, mm/h4.4 (4.0 – 4.8)3.7 (3.4 – 4.0)0.84 (0.78 – 0.90)0.001Note. CI – confidence interval. * Ratios of paired observations (95% CI). ** P-value calculated in paired samples t-test.Conclusion:Simultaneous vaccination against pneumococcal (PCV13) and Hib-infections in children with JIA produced no negative dynamics of the traditional indicators of disease activity (joint activity, uveitis, high ESR). At the same time, 3 weeks after vaccination, an increase in the concentration of calprotectin and hsCRP was found in a small number of patients (Disclosure of Interests:None declared

Background:Results from various phase 3 clinical studies have demonstrated the efficacy of canakinumab to treat patients with systemic juvenile idiopathic arthirtis (sJIA). However, limited information is available on the long-term efficacy and safety of this drug to treat children with sJIA.Objectives:To evaluate the long-term efficacy and safety of canakinumab in patients with sJIA treated at the National Medical Research Center of Children`s health, Moscow, Russia.Methods:This was a prospective, single-center study that included canakinumab (CAN)-naive patients diagnosed with sJIA following the International League of Associations for Rheumatology (ILAR) criteria and start receiving CAN treatment from 10/2012 to 03/2016. Patients included in this study also participated, for defined periods of time, in the clinical trialNCT02296424. Patients with active disease started treatment with canakinumab 4 mg/kg. A treat-to-target approach was used, canakinumab was discontinued in patients on clinical remission, either following theNCT02296424protocol or by investigator’s decision, and re-introduced in those patients who experienced a relapse afterwards. Disease characteristics and demographics were recorded at the time of diagnosis and initiation of treatment (study entry). Disease activity was evaluated periodically using the adaptedJIAACR core set measures, and percentages of patients with inactive disease and on clinical remission were calculated using the sJIA ACR criteria. Response to treatment was also evaluated by calculating modified ACR responses and JADAS-71 scores. Safety was assessed by collecting and classifying adverse events (AEs) at each visit.Results:Nineteen patients presenting with sJIA were included in this study, with a median age at treatment initiation of 9.6 (interquartile range, IQR 6.4-11.1) years and a median disease duration of 4.4 (IQR 1.2-7.0) years. Most patients (17/19) had been treated previously with one or more biologic agents for sJIA. As of 23 December of 2019, the median time of follow up was 55.5 (47-71.7) months, with all patients being followed for at least 3.5 years and 5 patients followed for more than 7 years. As it is shown in figure 1, most patients (16/19) were on clinical remission one year after starting therapy, and this effect was sustained at year 3.5 (17/19). ACR 90 responses were observed in 84.2% (16/19) patients at one year and 94.7% (18/19) patients at 3.5 years, whereas JADAS-71 scores decreased from 15 (14: 28.5) at baseline to 0 (0: 0) at one year with 4/19 patients maintained with JADAS-71 >0); at 3.5 years, only one patient had JADAS-71>0 (0.47, due to slight ESR increasing). Concerning the 5 patients with >7 years of follow up, three of them were in clinical remission for more than 3 years, including one who had discontinued therapy more than 2 years. Another patient had a relapse after attempting drug discontinuation, but recovered clinical remission after reintroducing canakinumab, and remained in this state for the last two years. The remaining patient has persistent low levels of disease activity during the last four years of follow up. AEs required hospitalization were reported in 36.8% (7/19) patients.Conclusion:Sustained clinical remission was observed in most patients with sJIA treated with canakinumab for up to 7 years, with no new or unexpected adverse events reported.Disclosure of Interests:Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Elizaveta Krekhova: None declared, Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Meyri Shingarova: None declared, Ivan Kriulin: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

Background:Early-onset form of systemic juvenile idiopathic arthritis (sJIA) often presents severe disease course. Choosing the optimal therapy option as first-line treatment is necessary for rapid improvement of patients’ quality of live and prevention of further radiologic progression.Objectives:To evaluate the long-term effectiveness and safety of tociliizumab (TOC) in sJIA patients depending on the duration of the disease treated in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:The study was conducted as a subanalysis of the prospective cohort study to evaluate the efficacy of biologics in children with sJIA. Analysis included sJIA patients younger than 4 years of age at the moment of TOC initiation. Patients were divided into 2 groups: with disease duration shorter than 6 month (ShorterDD group, n=35) and more than 6 month (LongerDD group, n= 19). Treatment efficacy was evaluated according to the dynamics of clinical and laboratory signs using the ACRPedi criteria. The Wallace criteria were used to evaluate whether or not remission had been achieved. Treatment safety was evaluated according to the data presented in the Adverse Event Reports.Results:TOC was first biologics in 34/35 (97.1%) patients in ShorterDD group and 18/19 (94.7%) patients in LongerDD group. Groups were comparable in terms of disease activity at TOC initiation with 100% of patients presented active systemic features. 31/35 (88.6%) patients in ShorterDD group and 17/19 (89.5%) patients in LongerDD group have median 3 (IQR 1: 6) and 5 (IQR 3: 7.5) active joints, respectively (p=0.119). JADAS-71 level was 17.14 ± 6.25 ShorterDD group and 17.36 ± 5.45 in LongerDD group (p=0.895).TOC showed high efficacy after first months of treatment with only 6/35 (17.1%) patients in ShorterDD group and 7/19 (36.8%) in LongerDD group remained with active systemic features (p=0.181). JADAS-71 level decreased to 0 points 26/35 patients (74.3%) in ShorterDD group and in 11/19 patients (57.9%) LongerDD group (p=0.237). After 3 month of treatment, WID was achieved by 27/35 patients (77.1%) in ShorterDD group and by 9/19 patients (47.4%) LongerDD group (p=0.038). ACR Pedi 50/70/90 was achieved by 88.6%/85.7%/80% of patients in ShorterDD group and by 84.2%/73.7%/68.4% of patients in LongerDD group after 1 months of treatment and in 77.1%/74.3%/74.3% and 84.2%/78.9%/68.4%, respectively, after 3 months of treatment.Conclusion:Initiation of tocilizumab treatment in sJIA patients under 4 years of age is highly effective. However, early treatment within first 6 month after disease onset had advantages in speed of reaching an inactive disease as soon as after 3 months of therapy.Disclosure of Interests:Elizaveta Krekhova: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared, Ivan Kriulin: None declared

Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

Background:Cryopyrine-associated periodic syndromes (CAPS) are a group of rare congenital auto-inflammatory diseases (AID) that include diseases such as familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and CINCA/NOMID syndrome. At present, there are limited data on demographic and clinical features of children with CAPS in Russia.Objectives:To reveal demographic, genotype and phenotype characteristics in CAPS patients at the National Medical Research Center of Children`s health, Moscow, Russia.Methods:Retrospective study included 12 patients (7 females, 58.3%) with CAPS confirmed by next generation sequencing (NGS). Median age of disease onset was 5.7 (interquartile range (IQR) 0.5:12.8) years. Characteristics of disease onset as well as dynamics of disease activity during long-term treatment were evaluated.Results:At the onset, systemic features were as follows: fever in 11 (91.6%) patients, rash in 8 (66.7%), hepatosplenomegaly in 7 (58.3%) patients, and lymphadenopathy in 6 (50%). Active arthritis in the onset of the disease was in 9/12 patients (75%), presented by polyarthritis in 7/9 (77.8%), and oligoarthritis in 2/9 (22.2%). Two patients (16.7%) had cataract, one (8.3%) had bilateral uveitis, and one (8.3%) had optic atrophy. Sensorineural hearing loss was observed only in 3/12 (25%). Hydrocephalus was detected in 3/12 (25%). Delayed mental and psycho-speech development was observed in 6/12 (50%) patients. In 3/12 (25%), the development of MAS was recorded.All patients had nucleotide variants inNLRP3gene. According to NGS results and clinical characteristics, 8/12 (66.7%) patients were diagnosed with MWS and 4/12 (33.3%) had CINCA/NOMID syndrome. In children with MWS, heterozygous variantc.2113C>AinNLRP3gene was the most common (5/8 (62.5%) patients). One of 8 (12.5%) patients with novel heterozygous variantc.2861C>Twas detected; also one child (12.5%) have heterozygous variantc.598G>Aand one (12.5%) – heterozygous variantc.943A>G. Four patients with CINCA/NOMID syndrome also had heterozygous variants inNLRP3gene:c.598G>A,c.2173C>A,c.1991T>Candc.796C>T.Prior to genetic testing, 12/12 (100%) patients received NSAIDs; 6/12 (50%) were treated with oral glucocorticoids (GC), 3/12 (25%) – with intravenous GC, 2/12 (22.2%) – with methotrexate. Biologics treatment included: 5/12 (41.7%) CAN, 4/12 (33.3%) tocilizumab, and 1/12 (8.3%) etanercept. After genetic testing, 7/12 (58.3%) patients were successfully switched to CAN. Only 1/12 (8.3%) child with MWS developed secondary inefficiency on CAN treatment.Conclusion:Systemic manifestations were detected in 91.6% of children, while active arthritis was observed in 75% of patients, which can cause difficulties in the diagnosis and treatment of CAPS. The effectiveness of canakinumab therapy was estimated in 91.6% of patients. The most frequent variant of theNLRP3gene in MWS wasc.2113C>A. In patients with CINCA/NOMID syndrome all nucleotide variants were individual.Disclosure of Interests:Meyri Shingarova: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Kirill Savostyanov: None declared, Aleksander Pushkov: None declared, Evgeniya Chistyakova: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Ivan Kriulin: None declared, Natalia Zhurkova: None declared, Rustam Tepaev: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared

Background The use of therapy with anti-cytokine biologicals in routine practice has significantly increased the percentage of children showing good response to therapy and reduced the time to achieve pharmacological remission. Nevertheless, the problem related to selecting the optimal drug for a certain patient still remains to be solved. Objectives This study was aimed at identifying clinical and laboratory parameters associated with response to tocilizumab (TOC) treatment in patients with RF-negative polyarticular JIA. Methods The prospective study to assess TOC efficacy involved 55 patients with RF-negative polyarticular JIA aged 9.42 years (IQR 5.96–13.42), with females (85.5%) predominating was conducted at the National Medical Research Centre of Children’s Health (Moscow). Treatment efficacy was evaluated using the ACRPedi criteria; Wallace’s criteria were used to assess whether a patient had reached inactive disease or remission. The potential baseline characteristics associated with treatment response were identified using univariate and multivariate logistic regression analyses. Baseline factors included the clinical, laboratory, and anamnestic data. Results TOC therapy showed high efficacy in children with RF-negative polyarticular JIA: 81.8/67.3/47.3/23.6% of patients reached the ACR30/50/70/90 criteria for the end of follow-up, respectively. The median time of achieving at least 30% improvement from baseline (ACR30) was 1 months (IQR 1:3). Univariate analysis showed that earlier age at initiation of Tocilizumab therapy, higher physician’s global assessment score using the 100-point Visual Analogue Scale, and longer morning stiffness were the factors associated with reaching ACR90. Younger age at therapy initiation, greater number of swollen joints and joints with limited range of motion, and history of using fewer biologicals are the factors associated with reaching inactive disease and remission. However, multifactorial analysis showed that only earlier age at initiation of TOC therapy was a statistically significant factor associated with reaching the best response to therapy in all the models. Conclusions Earlier initiation of TOC therapy is associated with higher chances for reaching ACR90 and pharmacological remission in patients with RF-negative polyarticular JIA. Further studies in larger cohorts are needed to identify the optimal age at therapy initiation. Disclosure of Interest E. Alexeeva: None declared, T. Dvoryakovskaya Grant/research support from: Roche, Pfizer, M. Soloshenko: None declared, R. Denisova: None declared, K. Isaeva: None declared, A. Mamutova: None declared, V. Gladkikh: None declared, A. Moskalev: None declared

Background Remission is the major goal of treatment of juvenile idiopathic arthritis(JIA). Advances in treatment options allowed achievement of remission to come into reach. Timing for initiating intensive treatment in a treat to target approach to early reach remission is still a debate. Objectives Multi-centre, double-blind, randomised study in polyarticular JIA patients (pts) receiving either Etanercept+Methotrexate (cohort 1) or Placebo +Methotrexate (cohort 2) for 24 weeks followed by 24 week open label phase. Escape to open-label ETN and MTX for pts not achieving paedACR30 at week 12 or not achieving inactive disease at week 24. Results 35 pts were randomised to cohort 1 and 33 to cohort 2. Baseline demographic and clinical characteristics were comparable between the groups except mean tender joint count, physician assessment of global disease activity and JADAS10 which all were higher in cohort 1. At week 12, 12 pts randomised to cohort 2 did not reach paedACR30. At week 24, further 10 pts of cohort 2 not reaching inactive disease escaped to ETA and MTX. 5 pts of cohort 1 and 4 pts of cohort 2 dropped out. At week 12, significantly more pts on ETA and MTX (33 (94%)/27 (79%)) than on PLC and MTX (17 (52%)/15 (47%) reached paedACR30/50 (p Conclusions Early combination of ETA and MTX proved to be highly effective with a high rate of patients reaching high paediatric ACR response and 50% reaching inactive disease. Pre-defined targets to treat to, paediatric ACR30 at week12, defining minimal response or inactive disease at week 24/48 were more often reached upon ETA and MTX than with MTX alone. Compared to immediate intense antirheumatic combination treatment with ETA and MTX, a comparable rate of patients on targeted therapy reached the final endpoint of inactive disease at week 48 but numbers of visits with active arthritis were higher in patients receiving delayed combination therapy. Reference [1] Wallace CA, et al. Arthritis Care Res2011;63:929–36. Acknowledgements The study was sponsored by an unrestricted grant by Pfizer, Russia Disclosure of Interest None declared

Background Development of biologics gives rise to novel classes of drugs, offering more options for treating children with primary or secondary failure of anti-TNF therapy. However, the question of whether or not previous exposure to biologic therapy and the number of previously administered biologics influence the efficacy of current treatment still needs to be solved. Objectives To compare tocilizumab efficacy in biologics-naive and biologics-switched patients with JIA. Methods Comparative analysis involved patients who had initiated TOC treatment at the National Medical Research Centre of Children’s Health (Moscow) depending on previous history of biologics therapy. Treatment efficacy was evaluated according to the dynamics of clinical and laboratory signs using the ACRPedi criteria. The Wallace criteria were used to evaluate whether or not remission had been achieved. Results Thirty-two patients were biologics-naive and 43 patients switched to TOC were previously treated with ETA (n=10), ADA (n=34), certolizumab (n=2), and infliximab (n=1). Children in the biologics-naive group differed from the switchers in a number of important baseline parameters: shorter disease duration (2.13 [1.25:5.34] and 7.42 [3:10.75] years, respectively; p 0.999). Conclusions Tocilizumab therapy is highly efficient both as the first and subsequent biologic agent. Children with history of therapy with at least one biologic agent have lower chances for achieving remission during the first 12 months of therapy. However, this difference is most likely caused by the longer and more severe arthritis course in children allocated to the group of biologics-switched patients compared to biologics-naive ones. Further matched large-cohort study is needed to identify predictors of response to therapy. Disclosure of Interest E. Alexeeva: None declared, T. Dvoryakovskaya Grant/research support from: Roche, Pfizer, M. Soloshenko: None declared, R. Denisova: None declared, K. Isaeva: None declared, A. Mamutova: None declared, V. Gladkikh: None declared, A. Moskalev: None declared

Background Juvenile idiopathic arthritis (JIA) is one of the most frequent and most disabling rheumatic diseases in children. Children with JIA receiving immunosuppressive and genetically engineered biologic drugs belong to the high-risk group for the development of bacterial and viral infections, including those administered by preventive vaccines. Objectives Our aim was to evaluate the tolerability of the pneumococcal 13-valent conjugate vaccine (PCV) in children with JIA. Methods In a prospective cohort study, 3 groups were formed: children with JIA in the remission phase on methotrexate or etanercept (group I), with JIA in the active phase prior to the appointment of methotrexate or etanercept (group II), control group (conditionally healthy children). 0.5 ml of the 13-valent PCV was administered once subcutaneously during therapy in patients in the remission phase or 3 weeks before the appointment of methotrexate or etanercept in patients in the active phase. Results At this stage of work, the tolerability of the 13 PCV vaccine was evaluated in patients with JIA, without systemic manifestations. In our study, the post-vaccination period was asymptomatic in 58% of the children in Group I, 66% in children in Group II, and in 60% in the control group. Most often in the postvaccinal period, local reactions were noted, which were painful at the place of administration of the vaccine in 6% of the children in group I, 8% in group II, and 24% in the control group, respectively. Less developed oedema and hyperemia at the injection site – in 12% of children in group I, 6% in group II, in 8% of children in the control group. There was no significant difference in the incidence of local reactions to vaccination of 13 PKV in patients with JIA and in children of the control group. Analysis of the time of occurrence and duration of local and systemic reactions to vaccination of 13 PKV showed that the maximum severity of symptoms was noted in the first day, by the 2–3 day of observation, complaints and fever disappeared. The increase in local reactions was noted 2 days after immunisation, followed by extinction to 3–4 days of follow-up. There were no serious adverse events in the post-vaccination period. Conclusions Vaccination with the 13-valent PCV in children with JIA is safety and is not accompanied by the development of serious adverse events. Disclosure of Interest E. Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, T. Dvoryakovskaya Grant/research support from: Roche, Pfizer, M. Soloshenko: None declared, R. Denisova: None declared, K. Isaeva: None declared, A. Mamutova: None declared, N. Mayansky: None declared, N. Tkachenko: None declared, I. Zubkova: None declared, T. Kaluzhnaya: None declared, A. Gayvoronskaya: None declared, M. Broeva: None declared, M. Fedoseenko: None declared