Retrospective Evaluation of Rabbit Anti-Thymocyte Globulin (rATG) Induction in Heart Transplant Patients

Abstract

Purpose The use and dosing intensity of rATG as induction therapy in heart transplantation remains controversial. We sought to evaluate the efficacy and safety of rATG at a total dose of 4.5mg/kg compared to less than 4.5mg/kg. Methods This study was a cross-sectional retrospective chart review of adults who underwent heart transplantation from January 1, 2016 - December 31, 2018 at a single quaternary care center. Exposure was defined as a full rATG (4.5mg/kg total) induction per institutional protocol compared to partial (less than 4.5mg/kg) induction. The primary outcome was the incidence of ISHLT 1990 defined acute cellular rejection (ACR) at two years. Secondary outcomes were all-cause mortality, proportion of infections, and time to therapeutic tacrolimus levels. Results A total of 201 patients met inclusion criteria. 61 received partial rATG induction and 140 received full rATG induction. When comparing partial vs full induction, there was no difference in any-grade of ACR (78.7% vs 88.6%, p=0.11). There was a trend toward a higher cumulative incidence of ACR grade 2 or above over two years in the partial as compared to the full induction group (18% vs 11.4%, p=0.21). On multivariate Cox PH analysis, partial vs full induction, the estimated hazard ratio was 1.45 (CI 0.62-3.37, p=0.39). Adjusted landmark survival analysis conditional on survival to 1 month showed no difference between the two groups. The number of patients with at least one infection within 3 months of transplant was similar between the groups (partial 29.5% vs full 20.0% p=0.20). Both groups achieved therapeutic tacrolimus levels by day 7 after initiation. Conclusion The dose of rATG does not appear to affect the overall incidence of biopsy-proven rejection, though there appears to be a trend towards severe rejection with rATG induction doses less than 4.5mg/kg. The total cumulative dose of rATG induction did not impact medium-term survival. Prospective, randomized, controlled trials are needed to validate these observations.