Evaluation of the Efficacy and Safety of Dual Induction versus Induction Monotherapy in Orthotopic Heart Transplant Recipients

Abstract

The goal of induction therapy with rabbit anti-thymocyte globulin (rATG) and basiliximab in cardiac transplant is to minimize incidence of biopsy-proven acute cellular rejection (BPAR). However, rATG has been associated with increased risk for hematologic and infectious complications. At Mayo Clinic, dual induction, consisting of rATG cumulative doses less than 6 mg/kg and basiliximab, has been utilized in recipients experiencing complications from rATG. The impact of dual induction in cardiac transplant recipients is unknown. The goal of this study was to evaluate the clinical outcomes associated with dual induction. This Institutional Review Board approved study was a retrospective review of cardiac transplant recipients who received induction therapy with rATG and/or basiliximab at Mayo Clinic in Florida between January 1, 2013 and December 31, 2017. The primary endpoint was time to first incidence of BPAR within 12 months following cardiac transplant. Secondary outcomes included time to first incidence of infectious complication, antibody-mediated rejection, and death within 12 months post-cardiac transplant. Additional secondary outcomes included time to first incidence of hematologic complication within 90 days post-cardiac transplant, time to first incidence of cytokine release syndrome and calcineurin inhibitor initiation within 14 days post-cardiac transplant. 102 cardiac transplant recipients were included. BPAR occurred in 79% patients receiving rATG induction, 90% patients receiving basiliximab induction, and 83% patients receiving dual induction. Basiliximab (HR, 1.85; 95% CI 1.06 to 3.23)and dual induction (HR, 1.81; 95% CI 1.04 to 3.15) were associated with higher risks of BPAR compared to rATG. Dual induction demonstrated an increased risk of infection, compared to both rATG (HR, 2.02; 95% CI 1.05 to 3.90) and basiliximab (HR, 3.46; 95% CI 1.31 - 9.1). Basiliximab was associated with a reduced risk of hematologic complication, compared to rATG (HR, 0.44; 95% CI 0.22 - 0.91), but an increased risk of mortality (HR, 4.32; 95% CI 1.2 to 16.1). Use of dual induction was associated with an increased risk of BPAR and infection post-transplant. Use of basiliximab demonstrated reduced risk of hematologic complications but increased risk of BPAR and mortality following transplant.