Posaconazole gastro-resistant tablets for preventing invasive fungal disease after hematopoietic stem cell transplantation: a propensity-matched cohort study

Abstract

ObjectivesTo evaluate posaconazole (POS) gastro-resistant tablets for preventing invasive fungal disease (IFD) in hematopoietic stem cell transplantation (HSCT) patients and analyze POS plasma concentrations. MethodsA single-arm trial was designed with a historical cohort as control. Patients aged 13 years and older undergoing HSCT at the HSCT Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS) from December 2020 to May 2022 were enrolled, prospectively taking POS gastro-resistant tablets orally from day 1 to 90 post-transplant and monitoring plasma concentrations. We also identified a retrospective cohort treated with alternative antifungal prophylaxis between January 2018 and December 2020, matched using propensity score methods. The primary outcome was the cumulative incidence of IFD at day 90 post-transplant. ResultsThe prospective study involved 144 patients receiving POS gastro-resistant tablets for IFD prevention, contrasting with 287 patients receiving non-POS tablets. By day 90 post-transplant, the POS tablet group exhibited a significantly lower cumulative incidence of IFD (2.81% [95% CI, 0.09%-5.50%] versus 7.69% [95% CI, 4.60%-10.78%]; P = 0.044). Adverse events were comparable between the groups, with liver changes in 33/144 (22.92%) versus 84/287 (29.27%) (P = 0.162), and renal injuries in 15/144 (10.41%) versus 37/287 (12.89%) (P = 0.457). Mean POS plasma concentrations on days 4, 8, 15, and 22post-administration were 930.97 ng/ml, 1143.97 ng/ml, 1569.8 ng/ml, and 1652.57 ng/ml, respectively. ConclusionPatients administered POS gastro-resistant tablets for antifungal prophylaxis experienced a lower cumulative incidence of IFD. POS plasma concentration in HSCT patients stabilized by day 15 of medication.