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BackgroundTreatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy.MethodsIn this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to ResultsA total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; pConclusionsSecukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis.Trial registration numberNCT03031782.

The COVID-19 vaccination has become a way of effective prevention of the decease for most people globally. However, there is a cohort of patients who are not able to form a full-fledged immune response due to primary or secondary immunodeficiency conditions caused by genetic disorders, severe course of chronic diseases, due to their age or the use of drugs that suppress the immune response. The use of monoclonal viral antibodies for immunocompromised patients is the most efficient method of pre- and post-contact and even long-term prevention, as well as the treatment of coronavirus infection. Monoclonal antibodies are obtained from B-lymphocytes of patients recovered from COVID-19. As a result of further modification aimed at increasing of the efficiency and reducing the risk of unwanted phenomena in the use, the virus-neutralizing recombinant monoclonal antibodies of the IgG1 class were designed to implement preventive and therapeutic schemes for COVID-19. Treatment of a new coronavirus infection with drugs with direct etiotropic action is most effective when prescribing in the early stages of the disease, which is especially relevant in patients at risk for a severe/critical clinical course of the disease and can be performed as outpatient clinical procedures. The article analyzes the results of clinical studies of efficacy and safety of mono- and combined drugs of monoclonal antibodies to SARS-CoV-2 in patients with the new coronavirus infection, as well as potential possibilities for their use for the treatment of COVID-19 caused by the new SARS-CoV-2 strains with multiple mutations on the example of the Omicron strain.

The biological agents when long-term clinical remission of juvenile idiopathic arthritis (JIA) is achieved is necessary to reduce the risk of side effects and costs and to minimize the non-economic burden of therapy on patients and their families. Objective. To evaluate the efficacy and safety of discontinuing inhibitors of tumor necrosis factor alpha (TNF-α) in patients with JIA without systemic manifestations due to long-term clinical remission. Patients and methods. A total of 137 patients with JIA (27.0% male, mean age: 10 years) were enrolled in this study, of whom 95 (69.3%) received etanercept (0.8 mg/kg/week) and the rest – adalimumab (24 mg/m2 once every two weeks). The retrospective study included patients with JIA without systemic manifestations and disease remission of ≥24 months, during which the patients received TNF-α inhibitors. The latter were discontinued as directed by a physician or due to unavailability of the drug. The primary outcome measure of the study was maintenance of clinically inactive disease status (according to American College of Rheumatology criteria) for 6 months (

The incidence of rheumatic diseases has been constantly growing during the last 20 years, which necessitates regular assessment of the healthcare quality for these patients and identification of the most significant problems and ways to address them. Juvenile idiopathic arthritis (JIA) is one of the most frequent disabling rheumatic diseases in children. The incidence and prevalence of JIA allow us to use this disorder to evaluate the organization of rheumatology care in general in terms of its accessibility and quality, as well as measures to improve it. This article reviews JIA epidemiology, characteristics and problems of healthcare organization for children with rheumatic diseases in the Russian Federation and other countries. Key words: healthcare organization, rheumatic diseases, health care, juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is one of the most common and disabling rheumatic diseases in children. Pharmaceutical therapy for JIA can prevent the progression of the disease, achieve long-term remission, and significantly improve the quality of life in most patients. In cases where the initial therapy for JIA is not effective enough, it is recommended to escalate it, and vice versa, when remission is achieved, the de-escalation of therapy may be discussed. The latter is necessary due to the high risk of developing infectious complications and certain oncological diseases against the background of continuous biological treatment of JIA, as well as the negative impact of regular injections and/or infusions of medications on the quality of life, the interruption of educational process, the psychological burden of “lifelong” treatment with medications, and the economic burden on families and healthcare system. Currently, optimal regimens for the discontinuation of biopharmaceuticals, including TNFalpha inhibitors, remain a matter of debate. In this regard, the search for potential predictors of JIA exacerbation after withdrawal of biopharmaceuticals is relevant. Key words: juvenile idiopathic arthritis, biologic-free remission of JIA, tumor necrosis factor, inhibitors, etanercept, adalimumab, withdrawal, exacerbation, predictors

Therapy with biologicals at the onset of systemic juvenile idiopathic arthritis (sJIA) ensures faster achievement of inactive disease or remission in more patients compared to standard treatment. Identification of predictors of early response to biologicals is necessary to increase treatment efficacy in children with sJIA. Objective. To develop a model for predicting treatment outcomes with different biologicals in sJIA patients. Materials and methods. We analyzed medical records of sJIA patients who received tocilizumab or canakinumab and were admitted to the Department of Rheumatology between July 2009 and February 2021. Predicted outcomes included inactive disease after 12 months of therapy with biologicals (according to C. Wallace criteria and JADAS71) and drug-free remission (without biologicals) for at least 6 months. Potential predictors comprised patient demographic and clinical characteristics, such as sJIA activity, CHAQ index, concomitant therapy, treatment outcomes after 1 and 3 months of therapy, etc. (115 parameters in total). Independent predictors were chosen using multivariate binary logistic regression. Results. This study included 250 patients receiving tocilizumab and 73 patients receiving canakinumab. After 12 months of tocilizumab therapy, 179 patients (76%) achieved inactive disease according to C. Wallace criteria and 170 patients (72%) achieved remission according to JADAS71 index. Drug-free remission (for at least 6 months without biologicals) was registered in 51 patients (20%) from the tocilizumab group. In the canakinumab group, inactive disease according to C. Wallace criteria, remission according to JADAS71, and drug-free remission were achieved in 58 (79%), 58 (79%), and 10 (14%) patients, respectively. Duration of morning stiffness at sJIA onset, dynamics of the duration of morning stiffness after 1 and 3 months of treatment, disease activity evaluated by a physician using the 100-mm visual analog scale (VAS) after one month of therapy, and patientreported overall well-being evaluated using VAS after 3 months of therapy were found to be the predictors of achieving remission according to C. Wallace criteria in the tocilizumab group. The following factors were significantly associated with remission according to JADAS71 index: duration of morning stiffness at sJIA onset and upon treatment initiation, VAS score evaluated by a physician after 1 and 3 months, and number of painful joints after 3 months. We also found several predictors of achieving drug-free remission, including lymphocyte count at disease onset, therapy with glucocorticoids (GCs) and its duration by the time of biological initiation, ESR upon treatment initiation, 50% improvement according to ACR pediatric criteria after 1 month, administration of systemic GCs after 1 month, ESR dynamics by 3 months, and number of joints with limited motion after 3 months. In the canakinumab group, the following factors were associated with remission according to C.Wallace criteria and JADAS71: duration of morning stiffness at treatment initiation, number of biologicals received in the past, 30% improvement according to pediatric ACR criteria after 1 month, and presence of joints with limited motion after 3 months; the predictors of drug-free remission included previous treatment with tocilizumab, number of active joints, and patient-reported overall well-being evaluated using VAS at treatment initiation, dynamics of the number of joints with active arthritis after 1 and 3 months, dynamics of JADAS71 after 1 month, lymphadenopathy after 1 month, and dynamics of patient-reported overall well-being after 3 months. Conclusion. Treatment in the past, characteristics of joint syndrome before and 1–3 months following treatment initiation, dynamics of laboratory parameters and VAS scores of disease activity (both patient-reported and physician-rated) were independent predictors of remission in sJIA patients during therapy with tocilizumab and canakinumab. Key words: systemic juvenile idiopathic arthritis, remission, predictors, biologicals, interleukin-1b inhibitor, interleukin-6 receptor inhibitor, tocilizumab, canakinumab

Background. Secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially fatal complication of systemic juvenile idiopathic arthritis (sJIA) characterized by hyperinflammation and a variety of clinical and laboratory manifestations. This condition is also referred to as macrophage activation syndrome (MAS) in patients with rheumatic diseases, including those with sJIA. In this article, we use the term sHLH. Approximately 40% of sHLH cases are asymptomatic, especially in patients who receive biologicals. Thus, the development of a prognostic model and identification of early sHLH markers in sJIA patients will enable timely initiation of anti-inflammatory and immunosuppressive therapy. Objective. To develop a prognostic model and identify early sHLH markers in sJIA patients. Methods. This study included 100 sJIA patients who were examined and treated in the Department of Rheumatology, National Medical Research Center for Children's Health between August 2010 and May 2021. A total of 114 sHLH episodes were registered among study participants. We analyzed medication history, as well as clinical and laboratory parameters reflecting the activity of sHLH and sJIA as potential early markers of sHLH. Multivariate logistic regression analysis was used to assess the predictive value of these markers for sHLH development. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for each factor to evaluate its significance. Receiver operating characteristic (ROC) curves were constructed to assess the sensitivity and specificity of the model. Results. We analyzed a number of factors as potential early sHLH markers, including medication history (treatment with oral or injectable glucocorticoids (GCs) before sHLH, immunosuppressants (methotrexate, cyclosporine, or leflunomide), and biologicals (tocilizumab, canakinumab, adalimumab, etanercept)), clinical signs (fever, rash, hepatomegaly, splenomegaly, lymphadenopathy, myalgia, hemorrhagic syndrome, central nervous system (CNS) lesions, kidney lesions, lung lesions, heart lesions), and laboratory parameters (hemoglobin, absolute count of red blood cells (RBCs), white blood cells (WBCs), neutrophils, lymphocytes, and platelets, erythrocyte sedimentation rate (ESR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), creatinine, blood urea, c-reactive protein (CRP), ferritin, triglycerides, procalcitonin (PCT), total protein, albumin, blood electrolytes (sodium, potassium, chlorides, iron), coagulation parameters (Quick prothrombin, thrombin time, prothrombin time, international normalized ratio (INR), partial thromboplastin time (APTT), D-dimer, fibrinogen, fibrin monomer, von Willebrand factor, protein S, and protein C). Our prognostic model demonstrated that the following variables were significant predictors of sHLH in sJIA patients: lymphadenopathy, red blood cell count 412 Units/L. The specificity of the model was 98.0%; the overall accuracy was 95.6%. The area under the ROC-curve (AUC) was 0.954 ± 0.027 (95% CI 0.902–1.000; р < 0.001). Conclusion. The most reliable prognostic markers of sHLH in sJIA patients are undoubtedly heterozygous mutations in the genes of primary (familial) hemophagocytic lymphohistiocytosis. In addition to that, lymphadenopathy, decreased RBC and platelet count, decreased serum level of chloride, and elevated serum LDH in sJIA patients can be interpreted as early sHLH markers and, therefore, considered as an indication to enhance anti-inflammatory and immunosuppressive therapy. Key words: secondary hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, early markers, prognostic model

Despite the positive developments in the sphere of ensuring the special needs of disabled children, a comprehensive socio-hygienic assessment of the conditions and lifestyles, as well as of their families, has not been carried out in the recent years. The purpose of the study is to identify, through a sociological survey, the problems that a disabled child encounters in his life, in order to further improve the provision of medical and social assistance to him. Materials and methods of research: 506 legal representatives of minors (aged 0–17 years) with the status of a disabled child were interviewed. Study design: single-center, non-randomized, uncontrolled. Results: the study of the living conditions of a disabled child in the family, the assessment by the parents of the state of his health, the problems arising during the registration of disability, in the provision of medical and rehabilitation assistance, and issues of medical and social support, made it possible to determine the position of this part of the child population in modern legal and medical and social conditions. The main problems were the large number of documents required for the registration of a disability, the long wait for the day of the examination, the remoteness of the location of the medical and social examination bureau, the shortage of specialist doctors, the problem with subsidized drugs, the lack of taking into account the individual needs of the child when carrying out rehabilitation programs, the need to contact different organizations and departments, lack of medical and social assistance, violation of rights in the provision of medical services to a disabled child. Conclusion: The acquired information is important for the further improvement of the provision of medical and social assistance to handicapped children and children with disabilities. The main task today is to develop mechanisms for fulfilling the declared rights and freedoms of persons with disabilities and the obligations undertaken by the state in relation to them. The principle of individualization of the provision of various benefits, depending on the condition of a disabled child, his needs, material security, remains relevant.

Interleukin-1β is one of the key cytokines mediating the development of clinical manifestations of systemic juvenile idiopathic arthritis (sJIA) in the early (febrile) and late phases of the disease. The implementation of interleukin-1β blockers into routine clinical practice has significantly changed the course of this severe disease. Objective. To assess the efficacy and safety of canakinumab in patients with sJIA. Patients and methods. This study included 73 sJIA patients who received canakinumab. Treatment was initiated in the Department of Rheumatology, National Medical Research Center for Children's Health (Moscow) between October 2012 and January 2020. The American College of Rheumatology (ACR) Pediatric criteria for assessing joint status (ACR Pedi 30, 50, 70, and 90) were used to evaluate treatment efficacy after one year of therapy. Inactive disease/remission was registered according to the С.Wallace criteria and the Juvenile Arthritis Disease Activity Score (JADAS71). Results. The majority of patients demonstrated an improvement after one year of therapy: 65 individuals (89%) according to ACR Pedi 30, 65 individuals (89%) according to ACR Pedi 50, 62 individuals (84,9%) according to ACR Pedi 70, and 61 individuals (83.6%) according to ACR Pedi 90. Inactive disease/remission according to JADAS71 and С.Wallace criteria was registered in 58 patients (79.45%). Conclusion. After one year of treatment, inactive disease/remission (С.Wallace and ACR Pedi 90 criteria) was achieved in 58 patients (79.45%) and 61 patients (83.6%), respectively. Long-term therapy with canakinumab was safe; the incidence of serious adverse events was 28.2 per 100 patient-years. Sustained remission without biologicals was observed in 7 out of 10 patients (13.7%), in whom there was an attempt to cease canakinumab. Key words: biologicals, interleukin-1β inhibitor, systemic juvenile idiopathic arthritis, inactive disease/remission, canakinumab, cytokines

Hemophagocytic lymphohistiocytosis (HLH), also known as cytokine storm, hemophagocytic lymphohistiocytosis, and macrophage activation syndrome, is a life-threatening disorder caused by a congenital or acquired defect in the cytolytic activity of cytotoxic T-lymphocytes (CD8+) and natural killers, as well as hyperproduction of interleukins-1, -6, -18, and interferon-γ. HLH develops in children with systemic juvenile idiopathic arthritis (sJIA), often resulting in multiple organ failure, and is characterized by a high risk of death. This article discusses the mechanisms underlying the development of primary and secondary HLH and sJIA, as well as clinical and laboratory manifestations of HLH. It summarizes the information on diagnostic criteria and analyzes therapeutic approaches used for HLH. Key words: hemophagocytic lymphohistiocytosis, systemic juvenile idiopathic arthritis, biologicals, rheumatology, children

The implementation of biologicals into routine clinical practice has significantly changed the course of systemic juvenile idiopathic arthritis (sJIA), substantially increased the efficacy of anti-rheumatic therapy, reduced steroid doses, and improved patients' quality of life. Objective. To assess the efficacy and safety of tocilizumab in patients with sJIA. Patients and methods. This study included 250 sJIA patients who received tocilizumab (258 prescriptions in total). Treatment was initiated in the Department of Rheumatology, National Medical Research Center for Children's Health (Moscow) between July 2009 and February 2021. The American College of Rheumatology (ACR) Pediatric criteria for assessing joint status (ACR Pedi 30, 50, 70, and 90) were used to evaluate treatment efficacy after one year of therapy. Inactive disease/remission was registered according to С.Wallace criteria and the Juvenile Arthritis Disease Activity Score (JADAS71). Results. The majority of patients demonstrated an improvement after one year of therapy: 200 individuals (84.4%) according to ACR Pedi 30, 197 individuals (83.1%) according to ACR Pedi 50, 192 individuals (81.0%) according to ACR Pedi 70, and 182 individuals (76.8%) according to ACR Pedi 90. Inactive disease/remission according to С.Wallace and JADAS71 criteria was registered in 179 patients (75.8%) and 170 patients (71.7%), respectively. Conclusion. After one year of treatment, inactive disease/remission according to ACR Pedi 90 criteria was achieved in 179 patients (75.8%) and 182 patients (76.8%), respectively. Therefore, good treatment results were observed in more than half sJIA patients receiving tocilizumab for a year. Nineteen patients achieved partial drug-free remission, whereas 32 patients achieved complete drug-free remission. Forty-two individuals reported no sJIA exacerbations during follow-up. Key words: biologicals, interleukin-6 receptor inhibitor, systemic juvenile idiopathic arthritis, inactive disease/remission, tocilizumab, cytokines

OBJECTIVE: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA). METHODS: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study. RESULTS: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified. CONCLUSION: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response. ispartof: ARTHRITIS & RHEUMATOLOGY vol:73 issue:2 pages:336-346 ispartof: location:United States status: published

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

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.

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

Background: A significant number of systemic juvenile idiopathic arthritis (sJIA) patients discontinue biologic disease-modifying antirheumatic drugs (DMARDs) due to lack of efficacy or safety concerns. Studies of biologic therapy switch regimens in sJIA are required.Methods: Patients with sJIA who switched from tocilizumab (due to lack of efficacy or safety) to canakinumab (4 mg/kg every 4 weeks) and were hospitalized at the rheumatology department from August 2012 to July 2020 were included. Primary efficacy outcomes were 30% or greater improvement based on the pediatric criteria of the American College of Rheumatology (ACR30), achievement of inactive disease (JADAS‑71 =0) and clinical remission (ACR sJIA clinical inactive disease criteria). Follow-up was 12 months or the closest time point (not less than 6 and not more than 18 months). Data were extracted from outpatient medical records.Results: During the study period, 46 patients with sJIA switched from tocilizumab to canakinumab. Median age at canakinumab initiation was 8.2 (interquartile range 4.0; 12.9) years, and median sJIA duration was 1.8 (0.8; 5.8) years; 37 (80%) patients received at least one non-biologic DMARD (oral corticosteroids, methotrexate and/or cyclosporine A). Study outcomes were followed up in 45 patients (one patient did not attend the follow-up for an unknown reason); median follow-up was 359 (282; 404) days. During the follow-up, canakinumab was discontinued in one patient (due to tuberculosis detection) and the dose was reduced or the injection interval increased in four (9%) patients. In total, 27 (60%) patients continued to receive at least one non-biologic DMARD. Improvement according to the ACR30 criteria was achieved in 43 patients (96%; 95% confidence interval, 85–99), inactive disease in 42 (93%; 82–98), and clinical remission in 37 (82%; 69‑91); after adjustment for actual time-at-risk, the rates were 83, 85 and 73 events per 100 person-years, respectively. During follow-up, 23 adverse events (most frequently infections) were reported in 19/45 (42%) patients; 5/45 (11%) patients developed macrophage activation syndrome, with a favorable outcome in all cases.Conclusions: Short-term (about 12 months) canakinumab therapy was found to be potentially effective as second-line biologic therapy after discontinuation of tocilizumab in patients with sJIA. Trial registration: CACZ885G2301E1 (G2301; NCT00891046 registered on April 29, 2009) and CACZ885G2306 (G2306; NCT02296424 registered on November 20, 2014).

Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis. Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months. Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement. Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.

ObjectiveTo investigate the frequency in which the physician provides a global assessment of disease activity (PhGA) >0 and an active joint count (AJC)=0 in children with juvenile idiopathic arthritis (JIA) and search for determinants of divergence between the two measures.MethodsData were extracted from a multinational cross-sectional dataset of 9966 patients who had JIA by International League of Associations for Rheumatology criteria, were recruited between 2011 and 2016, and had both PhGA and AJC recorded by the caring paediatric rheumatologist at the study visit. Determinants of discordance between PhGA>0 and AJC=0 were searched for by multivariable logistic regression and dominance analyses.ResultsThe PhGA was scored >0 in 1647 (32.3%) of 5103 patients who had an AJC of 0. Independent associations with discordant assessment were identified for tender or restricted joint count >0, history of enthesitis, presence of active uveitis or systemic features, enthesitis-related or systemic arthritis, increased acute phase reactants, pain visual analogue scale (VAS)>0, and impaired physical or psychosocial well-being. In dominance analysis, tender joint count accounted for 35.43% of PhGA variance, followed by pain VAS>0 (17.72%), restricted joint count >0 (16.14%) and physical health score >0 (11.42%).ConclusionWe found that many paediatric rheumatologists did not mark a score of 0 for patients who they found not to have active joints. The presence of pain in joints not meeting the definition of active joint used in JIA was the main determinant of this phenomenon.

Objective.To determine whether neutropenia is associated with increased risk for infection in patients with systemic juvenile idiopathic arthritis (sJIA) and polyarticular-course juvenile idiopathic arthritis (pcJIA) treated with tocilizumab (TCZ).Methods.Data up to Week 104 from 2 phase III trials of intravenous TCZ in sJIA (n = 112;ClinicalTrials.gov,NCT00642460) and pcJIA (n = 188;ClinicalTrials.gov,NCT00988221) were pooled. Worst common toxicity criteria grade and lowest observed absolute neutrophil count (ANC) were identified for each patient. Associations between patient characteristics and lowest observed ANC were tested using univariate regression analysis. Infection and serious infection rates per 100 patient-years (PY) in periods associated with grades 1/2 and 3/4 neutrophil counts were compared with rates associated with normal neutrophil counts.Results.ANC decreased to grade ≥ 3 in 25.0% and 5.9% of sJIA and pcJIA patients, respectively, and decreases were transient. Young age (p = 0.047) and methotrexate use (p = 0.012) were positively associated with neutropenia in patients with sJIA but not in patients with pcJIA. The rate of serious infections in patients with sJIA (10.9/100 PY; 95% CI 6.8–16.5) tended to be higher than in patients with pcJIA (5.2/100 PY; 95% CI 3–8.5). No increase in rates of serious or nonserious infections was observed during periods of neutropenia in either trial.Conclusion.Patients with JIA treated with TCZ experienced transient neutropenia that was not associated with an increased number of infections.

Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.

Context Glucocorticoids (GCs) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. Objective This study aims to determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). Methods Children aged 5 to 17 years with GIO were enrolled in this multinational, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT 00799266). Eligible children were randomly assigned 1:1 to 6 monthly IV ZA 0.05 mg/kg or IV placebo. The primary end point was the change in lumbar spine bone mineral density z score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. Results Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). LSBMDZ increased from −2.13 ± 0.79 to −1.49 ± 1.05 on ZA, compared with −2.38 ± 0.90 to −2.27 ± 1.03 on placebo (least squares means difference 0.41 [95% CI, 0.02-0.81; P = .04]); when corrected for height z score, the least squares means difference in LBMDZ was 0.75 [95% CI, 0.27-1.22; P = .004]. Two children on placebo had new low-trauma VF vs none on ZA. Adverse events (AEs) were reported in 15 of 18 children (83%) on ZA, and in 12 of 16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths or treatment discontinuations due to treatment-emergent AEs. Conclusion LSBMDZ increased significantly on ZA compared with placebo over 1 year in children with GIO. Most AEs occurred after the first infusion.

This article is devoted to the study of how religious identity and belonging to a religious community becomes a life strategy for socialization, and can help to overcome crises at different stages of life. The text presents an analysis of the autobiographies of those who made religiosity the basis of their way of life and a means of of self-determination. The methodological basis of the research is the combination of the theory of multiple modernities and the method of biographical interviews. Namely, we pay attention to the strategy of constructing religious identity. Sampling was carried out using a combination of reference sampling methods and ‘snowball’, since our previous experience has shown that this combination gives the best results in the study of hard-to-reach religious groups. In total, the sample included 30 respondents at the rate of three representatives of each denomination (Orthodox, Catholics, old believers, Buddhists, Jews) in each of the two cities. They were interviews (in person and on Skype), then the resulting transcripts were processed according to the methodology of the analysis of biographical narrative, described by T. Ingrata. The method of biographical interview removes the problem of psychological barrier in respondents when communicating on sensitive topics, as Hyde does not affect them directly. When planning the sample, we included major denominations represented in Russia — Orthodoxy, Catholicism, Buddhism and Judaism. This procedure allows identifying and describing strategies of behavior, as it is based on the comparison of biographical data of respondents with the ‘told life story’, that is, the consideration of subjective experience in comparison with the real socio-cultural context. Keywords: religious conversion, life crisis, biography, biography method

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 ...

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

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:Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two ILAR categories of juvenile idiopathic arthritis (JIA) and represent paediatric correlates of axial spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively.1,2 Secukinumab (SEC) has demonstrated efficacy and safety in adult patients (pts) with PsA, ankylosing spondylitis and non-radiographic axSpA.3-5Objectives:Evaluate efficacy and safety of SEC using a flare prevention design in pts with active ERA and JPsA.Methods:This 2-yr study consisted of an open-label (OL) s.c. SEC (75/150 mg in pts P-value for the Stratified log-rank test. KM estimates of the probability to disease flare by treatment groups in TP2 were plotted against days. Observed data were used in all analyses. Post-hoc analyses using non-responder imputation (NRI) were performed for JIA ACR 30/50/70/90/100 responses.Results:86/97 (89%) pts were enrolled in the OL period TP1 (mean age, 13.1 yrs; female, 33.7%; ERA, n=52; JPsA, n=34). At BL, mean JADAS-27 score was 15.1 and enthesitis count was 2.6. At the end of TP1, 90.4% (75/83) of pts achieved JIA ACR 30 and 69.9% (58/83) achieved JIA ACR 70. There were 21 and 10 flares in TP2, respectively in PBO and SEC treated pts with a significantly longer time to flare and 72% risk of flare reduction in SEC treatment vs PBO (HR: 0.28; 95% CI: 0.13–0.63; PTable 1.Efficacy of secukinumab in Treatment Periods 1 and 2 (Key secondary endpoints)Efficacy Outcomes, %TP1TP2¥SEC (N=83)^SEC (N=37)PBO (N=37)P-valueJIA ACR 3090.489.264.90.014JIA ACR 5086.778.462.20.152JIA ACR 7069.967.643.20.042JIA ACR 9039.851.440.50.431JIA ACR 10025.343.237.80.745Inactive disease#36.147.237.80.500JADAS-27, mean (SD)15.1 (7.2)14.6 (8.1)13.3 (5.8)NAEnthesitis count, mean change from BL (SD)−1.8 (2.3)−2.1 (2.0)−1.9 (1.2)NAP-values: Cochran-Mantel-Haenszel test, adjusted for analysis factors: JIA category (ERA/ JPsA) and MTX use at BL¥The N numbers are values at the end of TP2^Efficacy outcomes (%) in TP1 calculated in patients with evaluable data at Wk 12 (N=83)#Inactive disease: Definition adapted from JIA ACR criteria of Wallace et al., 2011. N=36 for SEC at the end of TP2JADAS, Juvenile Arthritis Disease Activity Score; N, total number of patients in the treatment group; NA, data not availableFigure 1.Time to flare in Treatment Period 2 (Primary Endpoint)Conclusion:In children and adolescents with ERA and JPsA, efficacy of SEC was demonstrated with a significantly longer time to flare vs PBO with sustained improvement of signs and symptoms up to Wk 104 and a favourable safety profile.References:[1]Colbert RA. Nat Rev Rheumatol. 2010;6:477–85.[2]Martini A, et al. J Rheumatol. 2019;46:190–7.[3]McInnes IB, et al. Lancet. 2015;386:1137–46.[4]Baeten D, et al. N Engl J Med. 2015;373:2534–48.[5]Deodhar A, et al. Arthritis Rheumatol. 2021;73:110–20.Disclosure of Interests:Nicolino Ruperto Consultant of: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi, Speakers bureau: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Ivan Foeldvari Consultant of: Novartis, Speakers bureau: Novartis, Ekaterina Alexeeva Grant/research support from: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, Speakers bureau: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, NURAY AKTAY AYAZ: None declared, Inmaculada Calvo Consultant of: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Speakers bureau: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Ozgur KASAPCOPUR: None declared, Vyacheslav Chasnyk: None declared, Markus Hufnagel Grant/research support from: Astellas, F. Hoffmann-La Roche, Novartis, Zbigniew Żuber: None declared, Grant Schulert Consultant of: Sobi, Novartis, Seza Ozen: None declared, Artem Popov: None declared, Athimalaipet Ramanan Speakers bureau: Roche, Sobi, Eli Lilly, UCB, Novartis, Christiaan Scott: None declared, Betül Sözeri: None declared, Elena Zholobova Grant/research support from: Pfizer, Novartis, Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Xuan Zhu Employee of: Novartis, sarah whelan Employee of: Novartis, Shareholder of: Novartis, Luminita Pricop Employee of: Novartis, Shareholder of: Novartis, Angelo Ravelli Consultant of: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Speakers bureau: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Alberto Martini Consultant of: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Speakers bureau: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Daniel J Lovell Consultant of: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Speakers bureau: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Hermine Brunner Consultant of: Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer, Grant/research support from: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer, Speakers bureau: Pfizer, Roche and GlaxoSmithKline

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

Background:Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 per 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is the largest multinational registry that prospectively collects information about jSSc patients.Objectives:Evaluation of the jSSc patients at the time of inclusion in the JSSIC.Methods:Patients were included in the JSSIC if they fulfilled the adult ACR/EULAR classification criteria for systemic scleroderma, if they presented the first non-Raynaud symptom before 16 years of age and if they were younger than 18 years of age at time of inclusion. Patients’ characteristics at time of inclusion were evaluated.Results:Until 15thof December 2019 hundred fifty patients were included, 83% of them being Caucasian and 80% female. The majority had the diffuse subtype (72%) and 17% of all jSSc had overlap features. The mean age of first presentation of Raynaud´s phenomenon was 9.8 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc) (p=.197). The mean age at first non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.2 years in the ljSSc (p=0.247). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group.Significant differences were found between the groups regarding mean modified Rodnan skin score, 18.2 in the djSSc vs 6.2 in the ljSSc (p=0.02); presence of Gottron´s papulae (djSSc 30% vs ljSSc 13%, p=0.43);presence of teleangiectasia (djSSc 42% vs 18% ljSS, p=0.01); history of ulceration (djSSc 42% vs 18% ljSSc,p=0.008); 6 Minute walk test below the 10thpercentile (djSSc 85% vs ljSSc 54%, p=0.044), total pulmonary involvement (djSSc 49% vs ljSSc 31%, p=0.045), cardiac involvement (ljSSc 17% vs djSSc 3%, p=0.002). djSSc patients had significantly worse scores for Physician Global Assessment of disease activity compared to ljSSc patients (VAS 0-100) (40 vs 15) (p=0.001) and for Physician Global Assessment of disease damage (VAS 0-100) (36 vs 17) (p=0.001).There were no statistically significant differences in the other presentations. Pulmonary hypertension occurred in approximately 6% in both groups. No systemic hypertension or renal crisis was reported. ANA positivity was 90% in both groups. Anti-Scl70 was positive in 35% in djSSc and 36% in the ljSSc group. Anticentromere positivity occurred in 3% in the djSSc and 7% in the ljSSc group.Conclusion:In this unique large cohort of jSSc patients there were significant differences between djSSc and ljSSc patients at time of inclusion into the cohort regarding skin, vascular, pulmonary and cardiac involvement. According to the physician global scores the djSSc patients had a significantly more severe disease. Interestingly the antibody profile was similar in both scleroderma phenotypes.Supported by the “Joachim Herz Stiftung”Disclosure of Interests: :Ivan Foeldvari Consultant of: Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Brian Feldman Consultant of: DSMB for Pfizer, OPTUM and AB2-Bio, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Maria Katsikas: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, edoardo marrani: None declared, Mikhail Kostik: None declared, Natalia Vasquez-Canizares: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Anjali Patwardhan: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Sujata Sawhney: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Blanca Bica: None declared, Juergen Brunner Grant/research support from: Pfizer, Novartis, Consultant of: Pfizer, Novartis, Abbvie, Roche, BMS, Speakers bureau: Pfizer, Novartis, Abbvie, Roche, BMS, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Daniela Kaiser: None declared, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Yosef Uziel: None declared, Nicola Helmus: 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

Background Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. There are limited data regarding the clinical presentation of jSSc. The Juvenile Systemic Scleroderma Inception Cohort (JSSIC) is a multinational registry that prospectively collects information regarding patients with this disease in a standardized manner. Objectives Evaluation of the jSSc patients at the time of inclusion in the JSSIC. Methods Patients were included in the JSSIC if they fulfilled the adult classification criteria, if they presented the first non Raynaud symptom before 16 years old and if they were younger than 18 years of age at the time of inclusion. Patients’ characteristics at time of inclusion were evaluated. Results Currently, the cohort includes 120 patients, being 89% Caucasian and 80% female. The majority had diffuse subtype (74%) and 18% had overlap features. The mean age of onset of Raynaud phenomenon was 9.7 years in the diffuse subtype (djSSc) and 10.7 years in the limited subtype (ljSSc). The mean age of non-Raynaud’s symptoms was 10.0 years in the djSSc and 11.4 years in the ljSSc (p=0.041). Mean disease duration at time of inclusion was 3.4 years in the djSSc and 2.4 years in the ljSSc group. Mean Modified Rodnan skin score was 17.5 in the djSSc and 7.3 in the ljSSc (p=0.002). Gottron papulae were significantly more common in the djSSc compared to ljSSc group (29% vs 6%, respectively) (p=0.011). History of ulceration was significantly more common in the djSSc than in the ljSSc group (57% vs 30%, respectively) (p=0.004). FVC Conclusion In this large cohort of jSSc patients there were surprisingly not many significant differences between djSSc and ljSSc. According to the physician global scores the djSSc patients have a significantly more severe disease. Disclosure of Interests Ivan Foeldvari Consultant for: Chugai, Novartis, Jens Klotsche: None declared, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Valda Stanevicha: None declared, Flavio R. Sztajnbok: None declared, Maria T. Tererri: None declared, Ekaterina Alexeeva: None declared, Jordi Anton Grant/research support from: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Consultant for: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Speakers bureau: Grant/research support, consultant or speakers bureau from AbbVie, Alexion, Bristol-Myers Squibb, ChemoCentryx, Gebro, GlaxoSmithKline, Novartis, Novimmune, Pfizer, Roche, Sanofi and Sobi, Maria Katsikas: None declared, Vanessa Smith: None declared, Tadej Avcin: None declared, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Thomas Lehman: None declared, Walter Alberto Sifuentes-Giraldo: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: None declared, Maria Jose Santos: None declared, Dieneke Schonenberg: None declared, Cristina Battagliotti: None declared, Lillemor Berntson: None declared, Blanca Bica: None declared, Juergen Brunner: None declared, Patricia Costa Reis: None declared, Despina Eleftheriou: None declared, Liora Harel: None declared, Gerd Horneff: None declared, Tilmann Kallinich Grant/research support from: Novartis, Speakers bureau: Sobi, Roche, Novartis, CLB, Dragana Lazarevic: None declared, Kirsten Minden Consultant for: AbbVie, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: None declared