Efficacy and safety of emapalumab in macrophage activation syndrome
Por:
De Benedetti F, Grom AA, Brogan PA, Bracaglia C, Pardeo M, Marucci G, Eleftheriou D, Papadopoulou C, Schulert GS, Quartier P, Anton-Lopez J, Laveille C, Frederiksen R, Asnaghi V, Ballabio M, Jacqmin P and de Min C
Publicada:
1 jun 2023
Ahead of Print:
1 mar 2023
Resumen:
Objectives Macrophage activation syndrome (MAS) is a severe, life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD). The objective of this study was to confirm the adequacy of an emapalumab dosing regimen in relation to interferon-? (IFN?) activity by assessing efficacy and safety. The efficacy outcome was MAS remission by week 8, based on clinical and laboratory criteria.Methods We studied emapalumab, a human anti-IFN? antibody, administered with background glucocorticoids, in a prospective single-arm trial involving patients who had MAS secondary to sJIA or AOSD and had previously failed high-dose glucocorticoids, with or without anakinra and/or ciclosporin. The study foresaw 4-week treatment that could be shortened or prolonged based on investigator's assessment of response. Patients entered a long-term (12 months) follow-up study.Results Fourteen patients received emapalumab. All patients completed the trial, entered the long-term follow-up and were alive at the end of follow-up. The investigated dosing regimen, based on an initial loading dose followed by maintenance doses, was appropriate, as shown by rapid neutralisation of IFN? activity, demonstrated by a prompt decrease in serum C-X-C motif chemokine ligand 9 (CXCL9) levels. By week 8, MAS remission was achieved in 13 of the 14 patients at a median time of 25 days. Viral infections and positive viral tests were observed.Conclusions Neutralisation of IFN? with emapalumab was efficacious in inducing remission of MAS secondary to sJIA or AOSD in patients who had failed high-dose glucocorticoids. Screening for viral infections should be performed, particularly for cytomegalovirus.
Filiaciones:
De Benedetti F:
Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy
Grom AA:
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Brogan PA:
University College London Great Ormond Street Institute of Child Health, London, UK
Eleftheriou D:
University College London Great Ormond Street Institute of Child Health, London, UK
Papadopoulou C:
University College London Great Ormond Street Institute of Child Health, London, UK
Schulert GS:
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA
Quartier P:
Pediatric Immuno-Hematology and Rheumatology Unit, RAISE Rare Disease Reference Centre, Hopital Universitaire Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, Paris, France
Université Paris-Cité, Paris, France
Anton-Lopez J:
Pediatric Rheumatology, Hospital Sant Joan de Deu, Barcelona, Spain
Faculty of Medicine, Universitat de Barcelona, Barcelona, Spain
Laveille C:
Calvagone Sarl, Liergues, France
Frederiksen R:
Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland
Asnaghi V:
Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland
Ballabio M:
Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland
Jacqmin P:
MnS Modelling and Simulation, Dinant, Belgium
de Min C:
Swedish Orphan Biovitrum AG (Sobi), Basel, Switzerland
Green Published, Green Submitted, hybrid
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