Early Switch From Tacrolimus to Everolimus After Liver Transplantation: Outcomes at 2 Years

Liver Transpl. 2019 Dec;25(12):1822-1832. doi: 10.1002/lt.25664.

Abstract

The observational CERTITUDE study follows liver transplant patients who completed the SIMCER trial. SIMCER randomized patients at month 1 after transplant to everolimus (EVR) with stepwise tacrolimus (TAC) withdrawal or to standard TAC, both with basiliximab induction and mycophenolic acid ± steroids. After completing SIMCER at 6 months after transplant, 65 EVR-treated patients and 78 TAC-treated patients entered CERTITUDE. At month 24 after transplant, 34/65 (52.3%) EVR-treated patients remained calcineurin inhibitor (CNI) free. Mean estimated glomerular filtration rate (eGFR) was significantly higher with EVR versus TAC during months 3-12. At month 24, eGFR values were 83.6 versus 75.3 mL/minute/1.73 m2 , respectively (P = 0.90) and adjusted mean change in eGFR from randomization was -8.0 versus -13.5 mL/minute/1.73 m2 (P = 0.15). At month 24, 45.9%, 31.1%, and 23.0% of EVR-treated patients had chronic kidney disease stages 1, 2, and 3, respectively, versus 25.7%, 45.7%, and 28.6% of TAC-treated patients (P = 0.05). Treated biopsy-proven acute rejection affected 4 EVR-treated patients and 2 TAC patients during months 6-24. Adverse events led to study discontinuation in 15.4% and 7.7% of EVR-treated and TAC-treated patients, respectively. Grade 3 or 4 hematological events were rare in both groups. A CNI-free EVR-based maintenance regimen appears feasible in approximately half of liver transplant patients. It preserves renal function effectively with good efficacy without compromising safety or hematological tolerance.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Drug Substitution*
  • Everolimus / adverse effects*
  • Feasibility Studies
  • Female
  • Follow-Up Studies
  • Graft Rejection / epidemiology*
  • Graft Rejection / immunology
  • Graft Rejection / prevention & control
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Humans
  • Immunosuppressive Agents / adverse effects*
  • Liver Transplantation / adverse effects
  • Male
  • Middle Aged
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency, Chronic / chemically induced
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / prevention & control
  • Severity of Illness Index
  • Tacrolimus / adverse effects*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Everolimus
  • Tacrolimus