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

Abstract

<h3>Purpose</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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. <h3>Conclusion</h3> 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.