IMMUNOSUPPRESSION IN LIVER TRANSPLANTATION

P. Trune?ka¹, O. Boillot², U. Neumann^3
1, IKEM, Prague/CZECH REPUBLIC, ², Hôpital Edouard Hérriot, Lyon/FRANCE, ³, Klinik Tranplantationschirurgie, Berlin/GERMANY

Body: Introduction: The aim of this study was to assess the long-term efficacy, safety and effect on renal function of once-daily prolonged-release tacrolimus (Tacrolimus QD) in liver transplant recipients. Methods: This was a multicentre, open, prospective, single-arm, additional 2-year follow-up study of Tacrolimus QD in adult transplant recipients who had already participated in a Phase III de novo liver study (11-03), for a duration of 12–23 months (mean time post-transplant approximately 17 months). Entry to this follow-up study was at the discretion of patient and investigator. Patients’ original immunosuppressive regimen was maintained unless medical needs necessitated otherwise. Primary endpoints were patient and graft survival; secondary endpoints included adverse events (AEs), BPAR incidence and renal function (Cockcroft–Gault). Results: Data are presented from the follow-up period only and do not include results from the original study. 130 out of 238 eligible patients entered this follow-up study, and 113 (86.9%) completed the 2-year period. There were 3 patient deaths during the follow-up (all considered not related to the study drug) and 14 (10.8%) withdrawals: due to an AE (5), switch to regimen not containing Tacrolimus QD (4), lost to follow-up (2), and withdrawal of consent, pregnancy, and prohibited medication (1 each). 74 (65.5%) completers were on Tacrolimus QD monotherapy at the end of the 2-year follow-up period and 16 (14.2%) were receiving Tacrolimus QD plus corticosteroids. Tacrolimus dosing and whole-blood trough levels decreased over time (Table 1). Patient and graft survival were both 95.4% during this 2-year follow-up. There were 3 graft losses, all due to death of the patient. BPAR was reported in 5 (3.8%) patients, 2 of which resolved spontaneously, and the 3 remaining were corticosteroid-sensitive. 2 episodes were mild, 2 moderate and 1 severe. Most commonly reported causally related AEs were hypertension (25.4%), renal insufficiency (18.5%), non-insulin dependent diabetes mellitus (10.0%), and hepatitis C infection (10.0%). The AE profile was similar to that expected with twice-daily tacrolimus. Renal function was stable throughout the 2-year follow-up period (Table 2). Conclusions: These results demonstrate that once-daily prolonged-release tacrolimus is efficacious and well tolerated in the long-term in patients treated de novo following liver transplantation without compromising renal function.

Disclosure: All authors have declared no conflicts of interest.