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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. 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. 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. 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). 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 (<10%). None declared Table 1Laboratory 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.

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: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: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 trial NCT02296424. 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 the NCT02296424 protocol 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 adapted JIA ACR 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

Construction of antibody mimetics on the base of alternative scaffold proteins is a promising strategy for obtaining new products for medicine and biotechnology. The aim of our work was to optimize the cell display system for the 10th human fibronectin type III domain (10Fn3) scaffold protein based on the AT877 autotransporter from Psychrobacter cryohalolentis K5T and to construct new artificial TNF-binding proteins. We obtained a 10Fn3 gene combinatorial library and screened it using the bacterial display method. After expression of the selected 10Fn3 variants in Escherichia coli cells and analysis of their TNF-binding activity, we identified proteins that display high affinity for TNF and characterized their properties.