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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.

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

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children (1). In adult patients there are significant differences between the clinical presentation of diffuse and limited subtypes (2). We reviewed clinical differences in presentation of subtypes in patients in the juvenile systemic scleroderma inception cohort up to 2021.ObjectivesTo study the clinical presentation of jSSc patients with diffuse (djSSc) and limited (ljSSc) subtypes.MethodsWe reviewed the clinical baseline characteristics of the patients, who were recruited to the juvenile scleroderma inception cohort (jSScC) (3, 4) till 1st of December 2021. jSScC is a prospective cohort of jSSc patients, who developed the first non-Raynaud´s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion.Results210 patients with jSSc were included in the cohort, 71% (n=162) had diffuse subtype. The median age at onset of Raynaud phenomenon was 10.4 years (7.3 – 12.9) and the median age at the first non-Raynaud symptom was 10.9 years (7.4 – 13.2). Median disease duration was 2.5 years (1 – 4.4) at the time of inclusion. The female/male ratio was significantly lower in the djSSc subtype (3.7:1 versus 5:1, p< -2 z score (20% versus 4%, p=0.003) and decreased joint range of motion (64% versus 46%, p=0.019). Patients with ljSSc had significantly higher rate of cardiac involvement (13% versus 2%, p=0.001).Regarding patient related outcomes djSSc patients had more severe disease, looking at patient reported global disease activity (VAS 0 – 100) (40 versus 25, p=0.039), patient reported global disease damage (VAS 0 – 100) (40 versus 25, p=0.021) and patient reported assessment of ulceration activity (10 versus 0, p=0.044). Regarding physician related outcomes the physician reported global disease activity (VAS 0 – 100) (32 versus 20, pConclusionIn this jSSc cohort, the largest in the world, djSSc patients have a significantly more severe disease than ljSSc patients. Interestingly, we found no differences regarding interstitial lung disease and pulmonary hypertension.References[1]Beukelman T, Xie F, Foeldvari I. Assessing the prevalence of juvenile systemic sclerosis in childhood using administrative claims data from the United States. Journal of Scleroderma and Related Disorders. 2018;3(2):189-90.[2]Dougherty DH, Kwakkenbos L, Carrier ME, Salazar G, Assassi S, Baron M, et al. The Scleroderma Patient-Centered Intervention Network Cohort: baseline clinical features and comparison with other large scleroderma cohorts. Rheumatology (Oxford). 2018;57(9):1623-31.[3]Foeldvari I, Klotsche J, Kasapcopur O, Adrovic A, Terreri MT, Sakamoto AP, et al. Differences sustained between diffuse and limited forms of juvenile systemic sclerosis in expanded international cohort. www.juvenile-scleroderma.com. Arthritis Care Res (Hoboken). 2021.[4]Foeldvari I, Klotsche J, Torok KS, Kasapcopur O, Adrovic A, Stanevica V, et al. CHARACTERISTICS OF THE FIRST 80 PATIENTS AT TIMEPOINT OF FIRST ASSESSMENT INCLUDED IN THE JUVENILE SYSTEMIC SCLEROSIS INCEPTION COHORT. WWW.JUVENILESCLERODERMA.COM. Journal of Scleroderma and Related Disorders. 2018;4(1-13).Disclosure of InterestsNone declared

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan autoimmune disease with a prevalence of 3 in 1 000 000 children. Information on long-term development of organ involvement and clinical characteristics of jSSc patients in adulthood are lacking. It was believed that patients in adult cohorts may represent a survival biased population.ObjectivesTo assess differences in clinical characteristics of jSSc-onset patients from the pediatric age group, with a mean disease duration of 3 years, compared to the adult age jSSc-onset group, with a mean disease duration of 18.5 years.MethodsWe extracted clinical data at time of inclusion into the cohorts from the Juvenile Scleroderma Inception Cohort (jSScC) and data from juvenile-onset adult SSc patients from the European Trials and Research Group (EUSTAR) cohort. We compared the clinical characteristics of the patients by descriptive statistics.ResultsWe extracted data of 187 jSSc patients from the jSScC and 236 patients from EUSTAR. The mean age at time of assessment was 13.4 years old in the jSScC and 32.4 years old in EUSTAR. The mean disease duration since first non-Raynaud was 3.0 years in jSScC and 18.5 years in the EUSTAR (Table 1).We found significant differences between the cohorts. There were more female patients in EUSTAR (87.7% versus 80.2%, p=0.04). More patients had diffuse subtype in jSScC (72.2% versus 40%, pTable 1.Clinical characteristics of juvenile onset SSc patients at time point of the inclusion into the juvenile scleroderma inception (jSScC) cohort and in the adult EUSTAR- cohortjSScCEUSTAR CohortP valueNumber of patients1872360.04Age in years, mean (SD)13.4 (3.6)32.4 (15.4)Female patients, n (%)150 (80.2%)207 (87.7%)jSSC Subtype, n (%)diffuse135 (72.2%)87 (38.1%)limited52 (27.8%)121 (53.3%)Age at Raynaud onset in years, mean (SD)10.0 (3.9)13.7 (9.1)Age at non-Raynaud onset in years, mean (SD)10.3 (3.9)11.7 (3.7)Duration since first Raynaud symptoms in years, mean (SD)3.4 (2.7)20.6 (15.9)Duration since first non-Raynaud symptoms in years, mean (SD)3.0 (2.7)18.5 (15.6)Raynaud´s, n (%)170 (90.9%)222 (94.9%)ANA positive, n (%)166 (91.7%)210 (92.9%)0.99Anti-Scl 70 positive, n (%)62 (34.4%)73 (33.3%)0.68Modified Rodnan Skin Score, mean (SD)5%Data missingModified Rodnan Skin Score, mean (SD)14.2 (11.7)12.1 (14.5)0.02Digital ulceration, n (%)At the time of inclusion33 (17.8)21 (26.6%)0.01In the past history100 (54.1%)34 (43%)Telangiectasia62 (37.4%)42 (53.2%)0.04FVC, mean (SD)84.1 (18.6)84 (22.4)0.96DLCO, mean (SD)75.4 (19.2)86.3 (19.9)Arterial hypertension, n (%)10 (5.4%)20 (8.5%)0.26Renal crisis, n (%)03 (1.3%)0.26Esophageal involvement, n (%)63 (33.7%)149 (63.7%)Intestinal involvement, n (%)62 (33.2%)56 (23.8%)0.04Articular involvement, n (%)34 (18.3%)27 (11.6%)0.06Muscular involvement, n (%)31 (19.3%)46 (19.8%)0.45ConclusionPatients with jSSc-onset who are currently adult age (defined as >18 years of age) are less frequently male and from the diffuse subset, have lower mRSS, less digital ulcers and intestinal involvement. This might represent a combination of both survival bias and/or be explained by the longer observation time with less active disease (i.e. natural progression decreased mRSS over time). Further long-term observational studies with jSSc patients are required to address this issue.Disclosure of InterestsNone declared

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

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of around 3 in 1, 000,000 children. It is known that in pediatric jSSc cohorts, there are a significant number of patients with overlap features, such as arthritis and myositis. However, the disease burden between those with and without overlap features in jSSc has not been defined.Objectives:Compare the clinical phenotype between children with and without overlap features in the juvenile systemic scleroderma inception cohort (jSScC).Methods:A cross-sectional study was performed using baseline visit data. Demographic, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were extracted from jSScC. Comparison between patients with and without overlap features was performed using chi-square test and Mann Whitney U-test.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s onset was 10 years (±3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Overlap features occurred 17% (n=30) of the cohort, 12.5% in the diffuse cutaneous (dc) jSSc and in 30% in the limited cutaneous (lc) jSSc. Significant differences in clinical characteristics were found between those patients with compared to without overlap characteristics. Patients with overlap features presented more frequently with Gottron papules (p=0.007), swollen joints (p=0.019), muscle weakness (p=0.003), and lung involvement documented by decreased DLCO < 80% (p=0.06) and/or abnormal high resolution computed tomography (p=0.049). Anti-PM/Scl autoantibodies were also more common in this group (p=0.001). Significantly more patients without overlap features had Raynaud´s (p=0.006). Physician Global Assessment of disease activity was significantly higher in patients with overlap features (41 vs 34; p=0.041). (Table 1.)Table 1.Demographic and clinical characteristics of jSSc patients with and without overlap features.Whole CohortN=175Patients without overlapN=145Patients with overlapN=30P valueFemale to Male Ratio 4.3:1(142/33)4:1(116/29)6.5:1(26/4)0.395Cutaneous subtypeDiffuse subtype (N)73% (128)11216Limited subtype (N)27% (47)3317Mean disease duration (years)3.1 (± 2.7)3.2 (± 2.8)3.1 (± 2.2)0.291Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud10.0 (± 3.8)10 non-Raynaud10.0 (± 3.7)7 non-Raynaud0.931Mean age of onset of non-Raynaud´s (years)10.2 (± 3.8)10.2 (± 3.9)9.8 (± 3.7)Disease modifying drugs (N)88% (154) 89% (129)83% (25)0.388Raynaud´s phenomenon90% (158)93% (135)77% (23)0.006Anti-PMScl18% (12/68)9% (5/53)47% (7/15)0.001Gottron Papules (N)27% (46/171)23% (33/144)48% (13/27)0.007DLCO 44% (39/88)39% (28/71)65% (11/17)0.06Abnormal findings in HRCT (N)44% (59/133)40% (43/107)62% (16/26)0.049Proportion of patients with swollen joints 18% (32) 14% (21) 37% (11)0.019Muscle Weakness (N) 21% (31/149)16% (20/123) 42% (11/26)0.003Physician global disease activity(0-100) min -max35 (0-90) n=14134 (0-90) n=11441 (0-80) n=270.041Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between patients with and without overlap features. Patients with overlap have significantly more interstitial lung disease and more physician rated disease activity and should not be considered to have more “mild disease”.Supported by the “Joachim Herz Stiftung”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:Juvenile systemic sclerosis (jSSc) is a rare disease with a prevalence of around 3 in 1,000,000 children. To better capture the clinical manifestations of jSSc the juvenile systemic sclerosis inception cohort (jSScC) has been prospectively enrolling patients with predetermined clinical variables over the past 12 years. One of the goals is to study the demographic, clinical features, and physician and patient reported outcome differences between those with juvenile limited cutaneous (lc) compared to diffuse cutaneous (dc) disease subtypes, to determine if characteristics are similar or different between dc and lc jSSc.Objectives:Evaluation of the baseline clinical characteristics of jSSc patients in the jSScC. Compare clinical phenotype between diffuse (dcjSSc) and limited cutaneous (lcjSSc) subtypes.Methods:Demographic, physical examination, organ system evaluation, autoantibody profile, treatment, and patient and physician reported outcome variables were evaluated from the jSSc Inception cohort and summary statistics applied using chi-square test and Mann Whitney U-test comparing lcjSSc and dcjSSc subtypes.Results:At the time of data extraction, 175 jSSc patients were enrolled in the cohort, 81% were Caucasian and 81% female. Diffuse cutaneous jSSc subtype predominated (73%). Mean disease duration was 3.1 year (±2.7). Mean age at Raynaud´s was 10 years (+3.8) and mean age of first non-Raynaud´s was 10.2 years (±3.8). Significant differences were found between dcjSSc versus lcjSSc, regarding several clinical characteristics. Patients with diffuse cutaneous subtype had significantly higher modified Rodnan skin score (p=0.001), presence of sclerodactyly (p=0.02), presence of Gottron’s papules (p=0.003), presence of telangiectasia (p=0.001), history of digital tip ulceration (p=0.01), and frequency of elevated CK value (p=0.04). Cardiac involvement was significantly higher in limited cutaneous jSSc subtype (p=0.02). Diffuse cutaneous jSSc patients had significantly worse scores for Physician Global Assessment of disease activity (38 vs 25; p=0.002) and disease damage (34 vs 19; p=0.008).Table 1.Comparison of demographic data and significant differences between dcjSSc and lcjSSc at time of inclusionWhole CohortN=175Diffuse SubtypeN=128Limited SubtypeN=47P valueFemale to Male Ratio4.3:1 (142/33)4.1:1 (103/25)4.8:1 (39/8)0.829Cutaneous subtypeDiffuse subtype73% (128)1280Limited subtype27% (47)047Mean Disease duration (years)3.1 (± 2.7)3.3 (± 2.9)2.6 (± 2.2)0.135Mean age of onset of Raynaud´s (years)10.0 (± 3.8)17 non-Raynaud9.8 (± 3.6)10 non-Raynaud10.6 (± 4.3)7 non-Raynaud0.219Mean age of onset of non-Raynaud´s (years)10.2 (± 3.9)10.0 (± 3.7)10.9 (± 4.3)0.173Disease modifying drugs88% (154)89% (114)85% (40)0.446CutaneousMean modified Rodnan skin score14.3 (0-51)17.4 (0-51)6.1 (0-24)0.001Gottron Papules27% (46/171)33% (41/124)11% (5)0.003Sclerodactyly78% (126/162)82% (98/119)65% (28/43)0.020Laboratory valuesElevated CK25% (30/122)30% (26/88)12% (4/34)0.041VascularTelangiectasia36% (56/154)44% (49/111)16% (7/43)0.001History of ulceration53% (91/173)61% (77/127)30% (14/46)0.001CardiacCardiac Involvement6% (10)2% (3)15% (7)0.002Patient Related OutcomesPhysician global disease activity(0-100) min -max35(0-90) n=14138(0-90) n=10825(0-80) n=330.002Physician global disease damage(0-100) min -max31(0-85) n=14034(0-85) n=10819(0-60) n=320.008Conclusion:Results from this large international cohort of jSSc patients demonstrate significant differences between dcjSSc and lcjSSc patients. According to the general organ involvement and physician global scores, the dcjSSc patients had significantly more severe disease. These observations strengthen our previous findings of the unique organ pattern of pediatric patients.Supported by the “Joachim Herz Stiftung”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:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence in around 3 in a million children. Pulmonary involvement in jSSc occurs in approximately 40 % in the inception cohort. Traditionally in jSSc, pulmonary function testing (PFT) with FVC and DLCO are used for screening and computed tomography (HRCT) was more reserved for those with abnormal PFTs. More recently, it has become apparent that PFTs might not be sensitive enough for detecting ILD in children.Objectives:Utilizing a prospective international juvenile systemic scleroderma cohort (JSScC) [2], to determine if pulmonary screening with FVC and DLCO is sufficient enough to assess the presence of interstitial lung disease in comparison to CT evaluation.Methods:The international juvenile systemic scleroderma cohort database was queried for available patients with recorded PFT parameters and HRCT performed to determine sensitivity of PFTs detecting disease process.Results:Of 129 patients in the jSScC, 67 patients had both CT imaging and an FVC reading from PFTs for direct comparison. DLCO readings were also captured but not in as many patients with tandem HRCT (n =55 DCLO and HRCT scan). Therefore, initial analyses focused on the sensitivity, specificity and accuracy of the FVC value from the PFTs to capture the diagnosis of interstitial lung disease as determined by HRCT.Overall, 49% of the patients had ILD determined by HRCT, with 60% of patients having normal FVC (>80%) with positive HRCT findings, and 24% of patients having normal DLCO (> 80%) with positive HRCT findings. Fourteen percent (n = 3/21) of patients with both FVC and DLCO values within the normal range had a positive HRCT finding.Conclusion:The sensitivity of the FVC in the JSScC cohort in detecting ILD was only 39%. Relying on PFTs alone for screening for ILD in juvenile systemic sclerosis would have missed the detection of ILD in almost 2/3 of the sample cohort, supporting the use of HRCT for detection of ILD in children with SSc. In addition, the cut off utilized, of less than 80% of predicted FVC or DLCO could be too low for pediatric patients to exclude beginning ILD. This pilot data needs confirmation in a larger patient population.Supported by the “Joachim Herz Stiftung”Disclosure of Interests:Ivan Foeldvari Consultant of: Novartis, Bernd Hinrichs: None declared, Kathryn Torok: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Valda Stanevicha: None declared, Flávio R. Sztajnbok: None declared, Maria T. Terreri: None declared, Ana Paula Sakamoto: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., 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, 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, Rolando Cimaz: None declared, Mikhail Kostik: None declared, Simone Appenzeller: None declared, Mahesh Janarthanan: None declared, Monika Moll: None declared, Dana Nemcova: 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, Dragana Lazarevic: None declared, Kirsten Minden Consultant of: GlaxoSmithKline, Sanofi, Speakers bureau: Roche, Susan Nielsen: None declared, Farzana Nuruzzaman: None declared, Anjali Patwardhan: None declared, Yosef Uziel: None declared, Nicola Helmus: 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

ObjectiveTo evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA).MethodsThis three-part, randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) ResultsIn part 1, 188 patients received tocilizumab (ConclusionsTocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis.Trial registration number:NCT00988221.