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

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