Defibrotide sodium for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Issue 2 (1st February 2018)

• Record Type: Journal Article
• Authors: Richardson, Paul G.; Triplett, Brandon M.; Ho, Vincent T.; Chao, Nelson; Dignan, Fiona L.; Maglio, Michelle; Mohty, Mohamad
• Is Part Of: Expert review of clinical pharmacology. Volume 11:Issue 2(2018)
• Page Start: 113
• Page End: 124
• Publication Date: 2018-02-01
• Subjects: Defibrotide -- endothelial cell activation -- fibrinolysis -- hematopoietic stem cell transplantation -- hepatic veno-occlusive disease -- multi-organ dysfunction -- multi-organ failure -- sinusoidal obstruction syndrome -- thrombosis; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2018.1421943
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: Introduction : Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is an unpredictable condition associated with endothelial-cell damage due to conditioning for hematopoietic stem-cell transplantation (HSCT) or chemotherapy without HSCT. Mortality in patients with VOD/SOS and multi-organ dysfunction (MOD) may be >80%. Areas covered : Defibrotide is the only approved drug for the treatment of severe hepatic VOD/SOS after HSCT in the European Union and hepatic VOD/SOS with renal or pulmonary dysfunction in the United States. Its efficacy in patients with VOD/SOS with MOD post-HSCT was demonstrated in a clinical-trial program that included a historically controlled treatment study, a phase 2 trial, and a large T-IND expanded-access program that also included patients without MOD and who received chemotherapy without HSCT. Expert commentary : Defibrotide appears to protect endothelial cells and restore the thrombolytic–fibrinolytic balance. It addresses a significant clinical need and has demonstrated favorable Day +100 survival and overall adverse-event rates that seem similar to control groups receiving supportive care alone. Currently, defibrotide is under investigation for the prevention of VOD/SOS in high-risk pediatric and adult patients.