Comparative effectiveness of thymoglobulin versus basiliximab for induction immunosuppression in older kidney transplant recipients: A target trial emulation

Introduction: Older kidney transplant (KT) recipients (≥65 years) are one of the fastest growing transplant populations worldwide and face heightened risks of immunosuppression-related morbidity, infections, and death, making the choice of induction immunosuppression (IS) particularly consequential. Thymoglobulin and basiliximab are both widely used, yet randomized trials of induction therapy have largely excluded older recipients, and existing observational studies are highly susceptible to confounding by indication. To overcome these limitations, we applied a target trial emulation framework to estimate the causal effects of thymoglobulin versus basiliximab induction on outcomes in older KT recipients.
Methods: We used US national registry data from USRDS to emulate a target trial comparing thymoglobulin versus basiliximab induction in KT recipients age ≥65 years (2010-2021) maintained on tacrolimus, mycophenolate, and steroids. The primary estimand was the average treatment effect (ATE), which is the expected causal effect if thymoglobulin (versus basiliximab) was assigned across the entire eligible population. Propensity score-based inverse probability weighting was used to emulate random treatment assignment by balancing donor and recipient characteristics. Outcomes included 5-year mortality, death-censored graft failure (DCGF), infection, length of stay (LOS), and 90-day readmission.
Results: We identified 10,353 patients who received thymoglobulin (57.4%) and 7,697 patients who received basiliximab (42.6%). Both groups were well balanced across donor and recipient characteristics. At 5 years, induction with thymoglobulin (compared to basiliximab) resulted in a 7% increase in mortality (HR 1.07, 95% CI 1.00-1.15, p=0.06) and an 11% increase in infection risk (HR 1.11, 95% CI 1.04-1.18, p=0.001). There was no difference in DCGF (HR 1.00, 95% CI 0.88-1.11, p=0.85). Additionally, thymoglobulin induction resulted in prolonged LOS (MR 1.07, 95% CI 1.05-1.08, p<0.001) and a 14% increase in 90-day readmission (OR 1.14, 95% CI 1.06-1.24, p<0.001). These results were robust across several sensitivity analyses, including an alternative causal estimand – the average treatment effect in the treated (ATT), which isolates the effect among those who actually received thymoglobulin.
Conclusion: Among older KT recipients who received standard triple-agent maintenance IS, induction with thymoglobulin compared with basiliximab causally increased mortality, infection, LOS, and 90-day readmission without any improvement in graft survival. These population-level estimates support preferential use of basiliximab over thymoglobulin for older KT recipients receiving standard maintenance IS and highlight an opportunity to optimize induction IS strategies and improve outcomes for this rapidly growing and vulnerable group of recipients.