Defibrotide for the treatment of severe hepatic veno-occlusive disease/sinusoidal obstruction syndrome: evidence for clinical benefit

作者：Richardson Paul G; Krishnan Amrita; Giralt Sergio; Soiffer Robert J

来源：Expert Opinion on Orphan Drugs, 2015, 3(12): 1491-1501.

DOI：10.1517/21678707.2015.1114455

• antithrombotic activity
• defibrotide
• endothelial dysfunction
• hematopoietic stem cell transplant
• hyperbilirubinemia
• multi-organ failure
• pro-fibrinolysis
• prophylaxis
• sinusoidal obstruction syndrome
• treatment
• veno-occlusive disease

Introduction: Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS), characterized by hepatic sinusoidal endothelial damage and liver dysfunction, is an unpredictable and potentially life-threatening complication of hematopoietic stem cell transplantation that occurs in an estimated 14% of these patients (range 0 - 62.3%). VOD/SOS typically occurs following high-dose radiotherapy and/or chemotherapy as conditioning. Although mild/moderate VOD/SOS may not progress in some patients and may resolve at an early stage (i.e., within 2 or 3weeks), in others it develops into severe VOD/SOS, commonly identified by the presence of multi-organ failure (defined by pulmonary and/or renal dysfunction), which, in turn, is associated with mortality rates >80%.Areas covered: This review of severe hepatic VOD/SOS discusses the disease characteristics, diagnostic criteria, prevalence, pathogenesis and current treatment guidelines for VOD/SOS, as well as prophylactic measures. The clinical trial evidence for associated therapies is reviewed, along with evaluations of these therapies by VOD/SOS expert consensus groups. Defibrotide, the only medication approved for the treatment of severe VOD/SOS in the European Union, is discussed in detail with regard to chemistry, pharmacodynamics/pharmacokinetics, proposed mechanisms of action and evidence from clinical trials of efficacy and safety.Expert opinion: Clinical data show that defibrotide reduces the mortality associated with VOD/SOS. Given the lack of therapeutic options and the favorable benefit/risk profile of defibrotide, this agent may therefore help fill an important and unmet therapeutic need.

• 出版日期2015-12-2