Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study

Long Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei Chen Lee, Kyung Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng Ren Yang, Gi Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy

Research output: Contribution to journalArticle

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Abstract

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7% (90% CI −5.2%, 3.7%); P <.001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P <.001 for non-inferiority), but not superiority and was similar between groups overall (mean −8.0 vs. −12.1 mL/min/1.73 m2, P =.108), and in patients continuing randomized treatment (−8.0 vs. −13.3 mL/min/1.73 m2, P =.046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria ≥1 g/24 h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.

Original languageEnglish
Pages (from-to)1435-1446
Number of pages12
JournalAmerican Journal of Transplantation
Volume18
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

Fingerprint

Living Donors
Tacrolimus
Multicenter Studies
Safety
Liver
Transplants
Recurrence
Liver Regeneration
Everolimus
Transplant Recipients
Random Allocation
Glomerular Filtration Rate
Proteinuria
Pharmaceutical Preparations
Hepatocellular Carcinoma
Kidney
Control Groups

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

Cite this

Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients : 12-month results of a randomized multicenter study. / Jeng, Long Bin; Lee, Sung Gyu; Soin, Arvinder Singh; Lee, Wei Chen; Suh, Kyung Suk; Joo, Dong Jin; Uemoto, Shinji; Joh, Jaewon; Yoshizumi, Tomoharu; Yang, Horng Ren; Song, Gi Won; Lopez, Patricia; Kochuparampil, Jossy; Sips, Carole; Kaneko, Shuhei; Levy, Gary.

In: American Journal of Transplantation, Vol. 18, No. 6, 01.06.2018, p. 1435-1446.

Research output: Contribution to journalArticle

Jeng, LB, Lee, SG, Soin, AS, Lee, WC, Suh, KS, Joo, DJ, Uemoto, S, Joh, J, Yoshizumi, T, Yang, HR, Song, GW, Lopez, P, Kochuparampil, J, Sips, C, Kaneko, S & Levy, G 2018, 'Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study', American Journal of Transplantation, vol. 18, no. 6, pp. 1435-1446. https://doi.org/10.1111/ajt.14623
Jeng, Long Bin ; Lee, Sung Gyu ; Soin, Arvinder Singh ; Lee, Wei Chen ; Suh, Kyung Suk ; Joo, Dong Jin ; Uemoto, Shinji ; Joh, Jaewon ; Yoshizumi, Tomoharu ; Yang, Horng Ren ; Song, Gi Won ; Lopez, Patricia ; Kochuparampil, Jossy ; Sips, Carole ; Kaneko, Shuhei ; Levy, Gary. / Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients : 12-month results of a randomized multicenter study. In: American Journal of Transplantation. 2018 ; Vol. 18, No. 6. pp. 1435-1446.
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abstract = "In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30 ± 5 days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months posttransplant: difference –0.7{\%} (90{\%} CI −5.2{\%}, 3.7{\%}); P <.001 for non-inferiority. Treated BPAR occurred in 2.2{\%} and 3.6{\%} of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P <.001 for non-inferiority), but not superiority and was similar between groups overall (mean −8.0 vs. −12.1 mL/min/1.73 m2, P =.108), and in patients continuing randomized treatment (−8.0 vs. −13.3 mL/min/1.73 m2, P =.046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5{\%} and 17.6{\%} of patients, adverse events with suspected relation to study drug occurred in 57.0{\%} and 40.4{\%}, and proteinuria ≥1 g/24 h in 9.3{\%} and 0{\%}, respectively. Everolimus did not negatively affect liver regeneration. At 12 months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1{\%}). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12 months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.",
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AU - Soin, Arvinder Singh

AU - Lee, Wei Chen

AU - Suh, Kyung Suk

AU - Joo, Dong Jin

AU - Uemoto, Shinji

AU - Joh, Jaewon

AU - Yoshizumi, Tomoharu

AU - Yang, Horng Ren

AU - Song, Gi Won

AU - Lopez, Patricia

AU - Kochuparampil, Jossy

AU - Sips, Carole

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AU - Levy, Gary

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