SAN FRANCISCO, CA—Adding everolimus (EVR) to reduced-tacrolimus (TAC) or eliminating TAC is associated with reduced long-term weight gain among patients who undergo liver transplantation, according to a study reported at the The Liver Meeting® 2015.
Obesity and post-transplant weight gain is believed to increase the risk of metabolic syndrome. “Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation significantly reduced weight gain at 1 and 2 years post-transplant,” reported lead study author Michael R. Charlton, MD, of the Intermountain Medical Center in Salt Lake City, UT, and coauthors.
He explained, “mTOR inhibitors have been shown to lead to lower body mass when compared to calcineurin inhibitors in animal studies. In contrast, calcineurin inhibitor-based immunosuppression is associated with steady weight gain in liver transplant recipients.”
In order to determine the impact of mTOR inhibition on weight gain following liver transplantation, the authors analyzed per-protocol data on weight change from baseline during 24 months among participants in a randomized, prospective, multicenter open-label study. Patients undergoing de novo liver transplantation were randomly assigned to undergo one of three immunosuppression-protocol regimens: EVR + reduced TAC (TAC: n=245 patients), TAC control (n=243), and TAC elimination (n=231), Dr. Charlton reported. The three treatment groups were “well-balanced in terms of age, gender, baseline weight, BMI, pre-transplant HCV infection and the incidence of diabetes,” he noted.
After a significantly elevated rate of treated biopsy-proven acute rejection (tBPAR) was identified among TAC elimination-group patients, recruitment to that study group was halted.
For patients who remained on treatment, mean increase in weight was significantly greater at Months 12 and 24 from baseline in the TAC control arm (8.43kg and 9.81kg, respectively) than in the EVR + reduced TAC (5.72kg and 6.52kg) and the TAC elimination (4.5kg and 5.26kg) groups (P=0.037–0.002).
“Study medication was discontinued due to adverse events in 28.6% of EVR + reduced TAC and 18.2% of TAC control patients,” he noted. Average daily prednisone doses were similar between the treatment arms. Frequency of cardiovascular events (P=0.312) and new onset diabetes mellitus (P=0.314) was similar between treatment arms but hyperlipidemia was more frequent in the EVR-containing arms (P<0.001).
“Longer follow-up is needed to determine the impact of the reduced weight on post-transplant metabolic syndrome and related outcomes,” concluded Dr. Charlton.