ABSTRACT FINAL ID: 1973
TITLE: Exposure to sofosbuvir and daclatasvir is unchanged in liver transplant patients on cyclosporine or tacrolimus based immunosuppression
SPONSORSHIP - THIS STUDY WAS SPONSORED BY: (IF THIS ABSTRACT WAS NOT SPONSORED PLEASE INDICATE):
This abstract was not sponsored.
The ANRS CO23 CUPILT study was funded by the Agence Nationale de Recherche sur le SIDA et les Hépatites (ANRS).
HCV recurrence is a main complication following liver transplantation (LT) impacting graft and patient survival. The recent approval of IFN-free regimen using direct antiviral agents (DAA) has radically changed the management of liver transplant recipients. However, the optimal strategy remains to be determined. The aim of this study was to assess the drug-drug interaction and tolerance between immunosuppressive therapy and DAA, sofosbuvir (SOF) and daclatasvir (DCV).
The ANRS CO23 CUPILT study is a prospective cohort including currently 699 patients (pts) with HCV recurrence and treated with 2nd generation DAA. Sixty-seven pts treated with SOF + DCV ± ribavirin (RBV) between Jul. 2013 and Nov. 2015 were included in this pharmacokinetic substudy. Patients should be on stable tacrolimus or cyclosporine-based immunosuppressive therapy at DAA initiation. Blood samples collected at week 2, 4, 12 and 24 were used to assay SOF, SOF main metabolite GS331007 and DAC using a validated LC-MS/MS method. Variation of quality controls inserted in all analytical runs were <15%. All results are expressed as mean and SD.
This substudy enrolled 67 liver recipients (male: 79%, mean age 57.4 ± 7.7 years), with an active HCV recurrence (G1: 51, G3: 9, G4: 7), in 14 centers. Treatment duration was 24 weeks (wk) in 92.5% of pts. RBV was given in 35 (52%) pts. All pts received cyclosporine (26%) or tacrolimus (74%).
At baseline, HCV viral load, GGT, creatinine clearance and hemoglobin levels were 6.4 ± 0.7 log10 IU/mL, 447.4 ± 743.8 IU/L, 73.3 ± 30.7 mL.min-1 and 13.4 ± 2.2 g/dL respectively.
Concentrations of DAA were measured at least once in all patients. One hundred forty five blood collections were assayed during DAA treatment, with an average 2.5 samples per patient. Intra-individual variability over the follow-up was 19% for SOF, GS331007 and 33% for DAC. SOF and GS331007 trough concentrations (99 blood collections) were 1.0 +- 1.5 ng/mL and 643.4 ± 406.9 ng/mL, respectively.
Though a 40% increase in DAC exposure was expected when co-administrated with cyclosporine, no difference in DAC trough concentrations was observed: 619.0 ± 578.4 ng/mL in cyclosporine treated patients (n=8) and 444.3 ± 498.4 ng/mL in tacrolimus treated patients.
SOF, GS and DCV concentrations in liver transplant patients were in the range of previously published study whether patients were on tacrolimus or cyclosporine based immunosuppressive therapy