Efficacy and Safety of Once-Daily Everolimus With Minimized Once-Daily Tacrolimus After Liver Transplantation

P. De Simone,¹ P. Carrai,¹ L. Coletti,¹ A. Precisi,² D. Campani,³ F. Filipponi.¹

¹Hepatobiliary Surgery and Liver Transplantation, University of Pisa Medical School Hospital, Pisa, Italy
²Laboratory, University of Pisa Medical School Hospital, Pisa, Italy
³Pathology, University of Pisa Medical School Hospital, Pisa, Italy.

Meeting: 2015 American Transplant Congress

Abstract number: A199

Keywords: Efficacy, Immunosuppression, Liver transplantation, Outcome

Session Information

Session Name: Poster Session A: Liver: Immunosuppression and Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

Background: The everolimus (EVR) pharmacokinetic profile allows for its once daily (OD) administration. We tested the efficacy and safety of a combination schedule of OD-EVR and reduced-exposure OD tacrolimus (rOD-TAC) with a pilot, prospective study in adult, maintenance (≥6 months) liver transplant (LT) recipients.

Materials and methods: Primary, deceased donor LT recipients on TAC-based immunosuppression were enrolled. Patients on OD-TAC were randomized to receive either OD-EVR (Group A; OD-EVR+rOD-TAC) or TD-EVR (Group B; TD-EVR+rOD-TAC). Patients on twice-daily TAC (TD-TAC) received TD-EVR only (Group C; TD-EVR+rTD-TAC) and were used as the referent case population. After EVR was in the target range (3-8 ng/mL), TAC exposure was minimized (3-5 ng/mL) for the entire duration of the study (12 months (M)). The primary endpoint was the 12-M efficacy failure rate, as the composite of treated biopsy proven acute rejection (tBPAR), graft loss, patient's death, and loss to follow-up. The secondary endpoint was the safety profile of the 3 combination regimens in the intent-to-treat (ITT) population.

Results: Fifty-four patients were allocated to the 3 treatment arms on a 1:1:1 basis (18 patients in each group). The 12-M composite efficacy rate was similar across groups (94.5% (A); 100% (B); and 100% (C), respectively; p=ns). One case of mild BPAR (RAI=6) was observed in Group A and C each, and there was only 1 death in Group C due to recurrent hepatocellular carcinoma. The most frequent adverse event was hyperlipidemia, with a 22.2%, 16.6%, and 16.6% incidence in Group A, B, and C, respectively (p=ns). Proteinuria ≥0.5/g was observed in 1 case in each Group (0.5%; p=ns). The endpoint (12M) renal function (4-MDRD eGFR) improved by 4.5 ± 7.6, 5.1 ± 6.2, and 5.7 ± 6.8 mL/min in Group A, B, and C, respectively (p=ns).

Conclusions: A full once-daily combination schedule of EVR and TAC allows for TAC minimization and shows comparable efficacy and safety vs. the twice-daily regimen.

To cite this abstract in AMA style:

Simone PDe, Carrai P, Coletti L, Precisi A, Campani D, Filipponi F. Efficacy and Safety of Once-Daily Everolimus With Minimized Once-Daily Tacrolimus After Liver Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/efficacy-and-safety-of-once-daily-everolimus-with-minimized-once-daily-tacrolimus-after-liver-transplantation/. Accessed May 31, 2025.

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