A SYSTEMATIC REVIEW FOR THE MANAGEMENT OF THE GENETICALLY DEFINED IL-1-MEDIATED AUTOINFLAMMATORY DISEASES, CAPS, TRAPS, MKD AND DIRA

Background: Ultra-rare genetically defined IL-1 mediated autoinflammatory diseases (AIDs) include mevalonate kinase deficiency (MKD), tumor necrosis factor receptor associated periodic syndrome (TRAPS), cryopyrinopathies (CAPS) and deficiency of the IL-1 receptor antagonist (DIRA). These disorders start perinatally, the clinical disease manifestations include systemic inflammation; and late diagnosis and inappropriate treatment cause irreversible organ damage. The varying skills of treating rheumatologists and paediatricians illustrate the need for management guidance, however criteria for validated methodology is geared towards common diseases with more heterogeneous pathogenesis. Objectives: The focus of this systematic review includes the evaluation of the existing literature and the evaluation of existing EULAR methodology for use in the ultra-rare diseases with defined pathomechanisms, CAPS, TRAPS, MKD and DIRA Methods: EULAR standardized operating procedures were followed during the review, including a meeting of experts to discuss key words, inclusion/exclusion criteria and PICO questions. Three fellows established the protocol of the review under the supervision of the EULAR methodologist and PubMed, Embase, and Cochrane databases were searched up to September 30, 2019. Results: We found 1582 articles for CAPS, 1109 articles for TRAPS,1741 articles for MKD and 557 articles for DIRA. Duplications, animal models and basic science studies, conference papers, systematic reviews/meta-analysis and articles not in English language is excluded. If we excluded case reports (n<4), then 72 articles for CAPS, 40 articles for TRAPS,44 articles for MKD and 1 article for DIRA should be included for full text evaluation and data extraction ( Figure 1 ). However among the case reports, patients excluded achieved complete remission, assessed by clinical criteria and biomarkers. Of the studies included only few randomized studies for CAPS, TRAPS, MKD, and DIRA and would achieve higher level of evidence ( Figure 1 ). Figure 1. Flow-charts of systematic review for CAPS, TRAPS and MKD. Conclusion: CAPS, TRAPS, MKD and DIRA are monogenic diseases with defined pathways and outcomes that include inflammatory remission based on clinical and biomarker data. Current methodological evaluations for genetically complex diseases undervalue the published evidence in case reports that report on remission and IL-1 biomarkers. We suggest that case studies that include hard outcomes including inflammatory remission, and open label withdrawal studies that are both backed by biomarkers could be allowed to be included and be considered for a stronger evidence level. REFERENCES: [1]van der Heijde D, Aletaha D, Carmona L, et al 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations Annals of the Rheumatic Diseases 2015;74:8-13. [2]Gattorno M, Hofer M, Federici S, Vanoni F, Bovis F, Aksentijevich I, Anton J, Arostegui JI, Barron K, Ben-Cherit E, Brogan PA, Cantarini L, Ceccherini I, De Benedetti F, Dedeoglu F, Demirkaya E, Frenkel J, Goldbach-Mansky R, Gul A, Hentgen V, Hoffman H, Kallinich T, Kone-Paut I, Kuemmerle-Deschner J, Lachmann HJ, Laxer RM, Livneh A, Obici L, Ozen S, Rowczenio D, Russo R, Shinar Y, Simon A, Toplak N, Touitou I, Uziel Y, van Gijn M, Foell D, Garassino C, Kastner D, Martini A, Sormani MP, Ruperto N; Eurofever Registry and the Paediatric Rheumatology International Trials Organisation (PRINTO). Classification criteria for autoinflammatory recurrent fevers. Ann Rheum Dis. 2019 Aug;78(8):1025-1032. Disclosure of Interests: Roberta Berard: None declared, micol romano: None declared, Zehra Serap Arici: None declared, David Piskin: None declared, Olcay Jones: None declared, Karen Durrant: None declared, Raphaela Goldbach-Mansky: None declared, Marco Gattorno Consultant of: Sobi, Novartis, Speakers bureau: Sobi, Novartis, Erkan Demirkaya: None declared Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 834Session: Other orphan diseases (Poster Presentations)