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Meta-Analysis
. 2022 Jun;42(6):465-476.
doi: 10.1007/s40261-022-01140-y. Epub 2022 May 20.

A Systematic Review and Meta-Analysis of Studies of Defibrotide Prophylaxis for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Selim Corbacioglu  1 , Ozlem Topaloglu  2 , Saurabh Aggarwal  2
Affiliations
Meta-Analysis

A Systematic Review and Meta-Analysis of Studies of Defibrotide Prophylaxis for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome

Selim Corbacioglu et al. Clin Drug Investig. 2022 Jun.

Abstract

Background and objectives: Defibrotide is approved to treat severe veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) after haematopoietic cell transplantation in patients aged > 1 month in the European Union and for VOD/SOS with renal/pulmonary dysfunction post-haematopoietic cell transplantation in the United States. This meta-analysis estimated the incidence and risk of VOD/SOS after intravenous defibrotide prophylaxis using the published literature.

Methods: PubMed, Embase and Web of Science were searched through 30 November 2021 for defibrotide studies in VOD/SOS "prevention" or "prophylaxis," excluding phase I studies, case reports, studies with fewer than ten patients and reviews.

Results: The search identified 733 records; 24 met inclusion criteria, of which 20 (N = 3005) evaluated intravenous defibrotide for VOD/SOS prophylaxis. Overall VOD/SOS incidence with intravenous defibrotide was 5%, with incidences of 5% in adults and 8% in paediatric patients. In eight studies with data on intravenous defibrotide prophylaxis vs controls (e.g. heparin, no prophylaxis), VOD/SOS incidence in controls was 16%. The risk ratio for developing VOD/SOS with defibrotide prophylaxis vs controls was 0.30 (95% confidence interval 0.12-0.71; p = 0.006).

Conclusions: This analysis suggests a low incidence of VOD/SOS following intravenous defibrotide prophylaxis, regardless of age group, and a lower relative risk for VOD/SOS with defibrotide prophylaxis vs controls in patient populations at high risk of VOD/SOS.

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Conflict of interest statement

SC has consulted for and received honoraria from Gentium/Jazz Pharmaceuticals. OT and SA have consulted for Jazz Pharmaceuticals.

Figures

Fig. 1
Fig. 1
Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) diagram of studies included and excluded. PK/PD pharmacokinetic/pharmacodynamic, VOD/SOS veno-occlusive disease/sinusoidal obstruction syndrome
Fig. 2
Fig. 2
Incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) with intravenous (IV) defibrotide prophylaxis [, , , , –, –, , , , –43]. CI confidence interval, ES effect size
Fig. 3
Fig. 3
Incidence of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) with intravenous (IV) defibrotide prophylaxis in adult (A) and paediatric (B) patients [, , , –27, 29, 30, 32, 33, 36, 38, 41, 42]. CI confidence interval, ES effect size. Five studies with IV defibrotide prophylaxis included patients of both age groups or did not specify age
Fig. 4
Fig. 4
Risk ratio of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) vs controls in intravenous (IV) defibrotide prophylaxis studies that included a control arm [6, 12, 13, 29, 33, 35, 41, 42] CI confidence interval. Note: Weights are from the random-effects analysis. aControl was no prophylaxis. bControl was heparin. cControl was without defibrotide. dControl was standard of care
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