Background. Long-term outcomes under EVR with MPA and no calcineurin inhibitor are undocumented after liver tx.

Methods. CERTITUDE is a prospective, multicenter, observational study of liver tx patients previously randomized at month 1 post-tx in the 6-month SIMCER trial to (i) EVR with tacrolimus (TAC) discontinued by month 4 or (ii) standard TAC, both with basiliximab induction, MPA and steroids. Patients will be followed to year 5 post-tx; data at 1 year post-tx are reported here.

Results. Of 188 patients randomized in SIMCER, 143 (76.1%) entered CERTITUDE (65/93 EVR, 78/95 TAC). The most frequent indications for tx were hepatitis C (n=75) and alcoholic cirrhosis (n=35); 124 were male. The primary endpoint, change in estimated GFR (eGFR, MDRD) from randomization to month 12 post-tx, was not significant in the EVR group (mean [SD] -4.7 [32.1] mL/min/1.73m², p=0.549) but showed a significant decrease in the TAC group (-11.7 [36.4] mL/min/1.73m², p=0.012). The difference in change in eGFR between groups was significantly in favor of EVR after adjustment for baseline eGFR (p<0.001). eGFR decreased by ≥10% in 35.5% and 51.9% of EVR- and TAC-treated patients, respectively (p=0.052). The incidence of biopsy-proven acute rejection (BPAR) from randomization to month 12 was 13.8% vs 6.4% for EVR vs TAC (p=0.136), with similar RAI scores (p=1.000). BPAR occurred in 6.2% of EVR patients vs 2.6% of TAC patients between months 6 to 12 (p=0.411). All BPAR episodes during months 6–12 were mild or indeterminate. Major adverse cardiac events occurred in no EVR-treated patients and 2 TAC-treated patients. There was one malignancy (bronchopulmonary carcinoma in the EVR group), which was fatal. No other deaths or graft losses occurred. Between months 6 and 12 post-tx, 7.7% and 1.3% of patients in the EVR and TAC groups, respectively, discontinued study drug due to adverse events.

Conclusions. Early conversion of liver tx recipients from TAC to EVR, with MPA and steroids, offers a sustained renal advantage vs standard TAC with an acceptable rate of BPAR. Longer follow-up of cardiovascular and malignancy outcomes is awaited.

CITATION INFORMATION: Saliba F, Duvoux C, Dharancy S, Dumortier J, Calmus Y, Di Giambattista F, Conti F. Long-Term Outcomes After Liver Transplantation (tx) with Everolimus (EVR) and Mycophenolic Acid (MPA) in a Calcineurin Inhibitor-Free Regimen: The CERTITUDE Trial. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress