title: Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.
abstract: In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.
authors.affiliation: Hepatobiliary Center, AP-HP Hôpital Paul Brousse, Université Paris-Sud, Villejuif, France. faouzi.saliba@pbr.aphp.fr
authors.forename: F
authors.initials: F
authors.lastname: Saliba
authors.forename: P
authors.initials: P
authors.lastname: De Simone
authors.forename: F
authors.initials: F
authors.lastname: Nevens
authors.forename: L
authors.initials: L
authors.lastname: De Carlis
authors.forename: H J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: S
authors.initials: S
authors.lastname: Beckebaum
authors.forename: S
authors.initials: S
authors.lastname: Jonas
authors.forename: D
authors.initials: D
authors.lastname: Sudan
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: C
authors.initials: C
authors.lastname: Duvoux
authors.forename: K D
authors.initials: KD
authors.lastname: Chavin
authors.forename: B
authors.initials: B
authors.lastname: Koneru
authors.forename: M A
authors.initials: MA
authors.lastname: Huang
authors.forename: W C
authors.initials: WC
authors.lastname: Chapman
authors.forename: D
authors.initials: D
authors.lastname: Foltys
authors.forename: G
authors.initials: G
authors.lastname: Dong
authors.forename: P M
authors.initials: PM
authors.lastname: Lopez
authors.forename: J
authors.initials: J
authors.lastname: Fung
authors.forename: G
authors.initials: G
authors.lastname: Junge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents; D004305:Dose-Response Relationship, Drug; D005060:Europe / Q000453:epidemiology; D000068338:Everolimus; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology*; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013020:South America / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D000068338:Everolimus; D020123:Sirolimus