Dr. Fabrizio De Benedetti, M.D., Ph.D. is a physician scientist who has been involved in both clinical activity and traslational research.

Education:

• July 1985: M.D. with Honors, School of Medicine at the Università degli Studi of Pavia
• June 1989: Board Certification in Pediatrics with Honors, Università degli Studi of Pavia
• December 1994: Ph.D. with Honors at the Università degli Studi of Pavia
• Present Employments:
• Since 2010: Head, Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Rome;
• Since 2002: Head, Laboratory of ImmunoRheumatology, Ospedale Pediatrico Bambino Gesù, Rome;
• Since 2022: Head of the Department of Immunology, Ospedale Pediatrico Bambino Gesù, Rome;

Clinical Activity:

Dr. De Benedetti is a pediatrician. His main focus has been pediatric rheumatology being involved in the diagnosis and treatment of children with rheumatic diseases since his residency. He has also been doing shifts in general Pediatrics and in pediatric Emergency while at the Pediatric Department in Pavia (1991-2002). Since he moved to the Ospedale Pediatrico Bambino Gesù in Rome, he was involved in Pediatric Rheumatology in the Department of Pediatric Medicine (2002-2010), and has also been part of the Unit of Rare Diseases (2004-2009). Since 2010 he is the head of the Division of Rheumatology at the Ospedale Pediatrico Bambino Gesù in Rome. He is also the head of the Research Department of Immunology and the Research Laboratory of ImmunoRheumatology at the Ospedale Pediatrico Bambino Gesù.

Teaching Activity:

Dr. De Benedetti was part of the educational program for Residents in Pediatrics (from 1999 to 2002) and Clinical Immunology (from 1994 to 2002) of the University of Pavia. After moving to Rome he was part of the education program for Residents in Rheumatology of the Catholic University (from 2003 to 2009). He is now part of the educational program for Residents in Pediatrics of the Università TorVergata (from 2008) of Università La Sapienza (from 2016) and of the Universita’ Cattolica del Sacro Cuore (from 2022) in Rome.

Scientific Activity:

Following his period at the National Cancer Institute, where he was involved in projects concerning the role of cytokines in the differentiation of tumor cells, Dr. De Benedetti’s research has focused on the pathogenesis and particularly on the role of inflammatory cytokines in pediatric inflammatory diseases.

His research has led to the identification of novel biomarkers of diagnosis, disease activity and prognosis in several rheumatic diseases of children and, more importantly, to the identification of novel therapeutic targets and the design and implementation of pivotal registration clinical trials. While leading the clinical division of Pediatric Rheumatology and the Laboratory of ImmunoRheumatology at the Ospedale Pediatrico Bambino Gesù, he has designed, and has coordinated or is coordinating, as lead international principal investigator, more than 10 pivotal Phase I/II/III clinical trials with novel targeted therapies in pediatric rheumatic diseases. He has authored more than 250 pubblications on peer-reviewed journals (h-index: 71 Scopus)

Scientific Societies:

Dr. De Benedetti is the Chair of the Scientific Council of PRESTAR, the clinical research network of the Pediatric Rheumatology European Society (PReS) and as such a member of the Council of PReS. He is member of the Scientific Committee of FOREUM. Dr. De Benedetti is the President of the Italian Society Pediatric Rheumatology (ReumaPed).

Main contributions to clinical and translational research

1) IL-6 in arthritis. His research identified in vivo and in vitro novel biological functions of interleukin-6 (IL-6) and provided the rationale for targeting IL-6 in some rheumatic diseases of children (PUB n. 5-8). These research findings were translated into novel design pivotal phase III clinical trials in systemic and polyarticular juvenile idiopathic arthritis (PUB n. 2-4). The results led to regulatory approval of tocilizumab by the FDA and the EMA for the treatment of children with systemic and polyarticular juvenile idiopathic arthritis. He is leading phase II-III trials with novel IL-6 inhibitors (ongoing).

2) Autoinflammation. He also focused on autoinflammatory diseases and on the role of the hyperproduction of IL-1. He designed and led an innovative, basket design, phase III clinical trial that led to the approval by the FDA and the EMA of canakinumab in three rare autoinflammatory fever syndromes (colchicine-resistant familial Mediterranean fever, mevalonate kinase deficiency and TNF-receptor associated periodic syndromes) (PUB n. 1). Recently he has coordinated an international team that identified a new autoinflammatory disease (PUB n.9)

3) IFN-gamma in primary and secondary HLH. More recently his research has moved to macrophage activation syndrome and hemophagocytic lymphohistiocytosis (MAS/HLH) with the identification of the pathogenic role of the IFNgamma pathway in animal models and in humans and the identification of novel biomarkers (PUB 10-15). He is part of the team who conducted the pivotal phase II-III study of the novel IFNgamma inhibitor, emapalumab, in primary HLH (PUB 14), that led to the approval by the FDA. He has designed, and is coordinating, as lead international principal investigator, the pivotal clinical trial with emapalumab in MAS in systemic JIA (PUB n. 16). He is now leading a basket trial of emapalumab in different hyperinflammatory syndromes. He has also designed and is leading as international lead principal investigator the phase 2 trial with a novel bispecific therapeutic monoclonal in patients with NLRC4 gain of function mutations and MAS/HLH.

4) Pediatric research. While working at the children Hospital in Rome, he has also been involved in research in several subspecialties of Pediatrics. Dr. De Benedetti led a number of collaborations in a variety of pediatric subspecialties, with the most relevant being neuromuscular diseases and nephrology(PUB n.17-19)

5) Recommendations and guidelines. Dr. De Benedetti has been involved in several multicenter international and national efforts aimed at performing clinical trials, defining outcome measures, drafting treatment recommendations and disease classification criteria (PUB 20-25). He is one of the 2 convenors of the ACR/EULAR points to consider for the early diagnosis and management of HLH/MAS and of the EULAR/PReS task force for diagnosis and management of sJIA and adult-onset Still disease (PUB 25)