Efficacy and safety of everolimus with reduced tacrolimus in living‐donor liver transplant recipients: 12‐month results of a randomized multicenter study |
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| Authors: | 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 |
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| Affiliation: | 1. China Medical University Hospital, Taichung, Taiwan;2. Asan Medical Center, Seoul, Republic of Korea;3. Medanta, Medicity Hospital, Gurgaon, India;4. Chang Gung Memorial Hospital, Tao‐Yuan, Lin‐Ko, Taiwan;5. Seoul National University College of Medicine, Seoul, Republic of Korea;6. Yonsei University College of Medicine, Severance Hospital, Seoul, Republic of Korea;7. Kyoto University Hospital, Kyoto, Japan;8. Samsung Medical Center, Seoul, Republic of Korea;9. Kyushu University Hospital, Fukuoka‐city, Japan;10. Novartis Pharma AG, Basel, Switzerland;11. Novartis Pharma KK, Tokyo, Japan;12. University of Toronto, Toronto, Canada |
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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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| Keywords: | clinical research/practice immunosuppressant ‐ mechanistic target of rapamycin (mTOR) immunosuppression/immune modulation lung (allograft) function/dysfunction |
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