Background: Scanty information is available on correlation between exposure to everolimus (EVR) and adverse events (AEs) for liver transplant (LT) recipients on immunosuppression regimens incorporating EVR. Materials and methods: This was a retrospective analysis of adult, LT recipients receiving EVR-based immunosuppression at a single center. Patients were included into current analysis if adult (³18 years) and with at least one EVR trough whole blood level. The primary study endpoints were incidence of AEs and correlation between exposure to EVR and AEs. AEs were imputed as either categorical or continuous variables, as appropriate. All AEs observed while on treatment with EVR or within 30 days after last EVR oral dose were considered treatment-related. Results: A total of 302 adult, LT recipients (mean [SD] age 51.2 [6.4] years; male 76.5%; mean [SD] time since transplantation 49.7 [11.6] months) who received EVR were included. At a median [range] follow-up of 41 [0-110] months after EVR introduction, 218 (72.2%) patients reported at least one AE. The most frequent AEs were: hypercholesterolemia in 63 patients (20.8%); infectious events in 31 (10.3%); oral ulcers in 24 (7.9%); leukopenia in 28 (9.3%); thrombocytopenia in 26 (8.6%), edema in 24 (7.9%), and wound complications in 16 (5.3%). Proteinuria ³2g/day was observed in 9 (3%) patients. A total of 65 (21.5%) patients discontinued EVR due to AEs. Complications associated with higher EVR exposure were hypercholesterolemia (r=0.65; p<0.0001), thrombocytopenia (r=-0.78; p<0.0001), and oral ulcers (r=0.63; p<0.0001). Infectious events (r=0.04; p=0.71), leukopenia (r=0.05; p=0.64), edema (r=0.04; p=0.67), wound complications (r=-0.05; p=0.68), and proteinuria (r=0.15; p=0.21) were not statistically correlated with higher EVR exposure. Conclusions: In patients on EVR-based immunosuppression, incidence of AEs is not always correlated with higher drug exposure. A linear exposure-effect correlation was observed only for hypercholesterolemia, thrombocytopenia, and oral sores.
Predicting adverse events in liver transplant patients on everolimus-based immunosuppression
De Simone P;Filipponi F
2016-01-01
Abstract
Background: Scanty information is available on correlation between exposure to everolimus (EVR) and adverse events (AEs) for liver transplant (LT) recipients on immunosuppression regimens incorporating EVR. Materials and methods: This was a retrospective analysis of adult, LT recipients receiving EVR-based immunosuppression at a single center. Patients were included into current analysis if adult (³18 years) and with at least one EVR trough whole blood level. The primary study endpoints were incidence of AEs and correlation between exposure to EVR and AEs. AEs were imputed as either categorical or continuous variables, as appropriate. All AEs observed while on treatment with EVR or within 30 days after last EVR oral dose were considered treatment-related. Results: A total of 302 adult, LT recipients (mean [SD] age 51.2 [6.4] years; male 76.5%; mean [SD] time since transplantation 49.7 [11.6] months) who received EVR were included. At a median [range] follow-up of 41 [0-110] months after EVR introduction, 218 (72.2%) patients reported at least one AE. The most frequent AEs were: hypercholesterolemia in 63 patients (20.8%); infectious events in 31 (10.3%); oral ulcers in 24 (7.9%); leukopenia in 28 (9.3%); thrombocytopenia in 26 (8.6%), edema in 24 (7.9%), and wound complications in 16 (5.3%). Proteinuria ³2g/day was observed in 9 (3%) patients. A total of 65 (21.5%) patients discontinued EVR due to AEs. Complications associated with higher EVR exposure were hypercholesterolemia (r=0.65; p<0.0001), thrombocytopenia (r=-0.78; p<0.0001), and oral ulcers (r=0.63; p<0.0001). Infectious events (r=0.04; p=0.71), leukopenia (r=0.05; p=0.64), edema (r=0.04; p=0.67), wound complications (r=-0.05; p=0.68), and proteinuria (r=0.15; p=0.21) were not statistically correlated with higher EVR exposure. Conclusions: In patients on EVR-based immunosuppression, incidence of AEs is not always correlated with higher drug exposure. A linear exposure-effect correlation was observed only for hypercholesterolemia, thrombocytopenia, and oral sores.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
