T-CELL ANTIBODY INDUCTION VERSUS CORTICOSTEROID INDUCTION FOR LIVER TRANSPLANT RECIPIENTS: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS WITH FOCUS ON DACLIZUMAB, BASILIXIMAB, AND RABBIT ANTI-THYMOCYTE GLOBULIN

Introduction There are wide disparities among transplant programs in terms of drugs used for induction of immunosuppression for liver transplantation (LT). T-cell antibody (TCA) induction regimens are used in several centers, while others use corticosteroids (CS) induction regimens. In this meta-analysis, we aim to compare the safety and efficacy of TCA and CS regimens. Methods We conducted a systematic review of Embase and Medline to identify randomized clinical trials comparing TCA induction regimens to CS induction regimens in patients undergoing LT. A meta-analysis of proportions and comparisons was performed. Results Screening of 2099 studies yielded 7 studies enrolling 1260 patients (Table 1). Four studies were comprised of only HCV infected patients. Overall, 427 patients had HCV infection. Daclizumab (DCZ) was compared to a CS induction regimen in three studies. Acute rejection rate was 22% (18-34%), with no significant difference in rejection rate in the DCZ and CS arms (RR 0.97; 0.78-1.20; I2 0%, p= 0.728; Table 2). There was no difference in risk of infectious adverse events (iAEs) in the DCZ and CS arms. The risk of de novo diabetes mellitus (dnDM) was lower in the DCZ arm compared to the CS arm (RR 0.45; 0.32-0.63; I2 33.2%, p= 0.221). The risk of HCV recurrence (rHCV) was lower in the DCZ arm compared to the CS arm (1 study, RR 0.54; 0.39-0.77; I2 0%, p= n/a). Graft survival within one year of LT was 89% (95%CI 86-91%), with no significant difference in graft survival in the DCZ arm and CS arm (0.98, 0.94-1.02, I2 78.5%, p= 0.010). Basiliximab (BSX) was compared to a BSX-free CS induction regimen in one trial and a BSX+CS based regimen in another trial. Acute graft rejection rate was 35% (25-45%), with no significant difference in rejection in the BSX and CS arms (RR 1.10; 0.78-1.20; I2 0%, p= 0.728). There was no significant different in the risk of iAEs, the risk of dnDM, and the risk of rHCV in the BSX and CS arms. There was no significant difference in graft survival within one year of transplant in the BSX and CS arms (RR 1.14; 0.98-1.32; I2 0%, p= 0.604). Overall survival (OS) within one year of LT slightly favored the BSX arm compared to the CS arm (RR 1.14; 95%CI 1-1.31; I2 31.1%, p=0.228). Rabbit anti-thymocyte globulin (rATG) was compared to CS induction regimens in two studies; the acute graft rejection rate was 20% (8-34%), with no significant difference in acute graft rejection in the rATG and CS arms (RR 0.67; 0.33-1.39; I2 0%, p=0.659). There was no significant difference in the risk of iAEs, dnDM, and rHCV in the rATG and CS arms. Conclusion TCA induction regimens are equally safe and efficacious compared to CS induction regimens in terms of graft rejection, infectious AEs, and graft survival within one-year of LT.