Evaluation of Antithymocyte Globulin and Basiliximab as Induction Therapy in Kidney Transplant Recipients




Bhalla, Arnav
Katasani, Hamsini
Herdrich, Kyle

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George Mason University


Background The roles of induction and maintenance therapies are becoming increasingly critical in promoting the long-term success of renal transplants and the reduction of post-surgery acute rejection. From 1998 to 2007, 78% of kidney transplant recipients (KTR) in the U.S. received immunosuppressive induction therapy [1]; fast forward to 2014, that percentage increased to 90%. [2] The three most popular antibodies used in induction therapy for KTRs in the U.S. are Antithymocyte Globulin (“Thymo”), Basiliximab (“Simulect”), and Alemtuzumab (“Campath”). According to Koyawala, et al., rabbit Thymo is used in approx. 50% of indication therapies for KTRs, Basiliximab 20%, and Campath 15%. [2] Thymo is a polyclonal antibody and lymphocytedepleting agent sourced from rabbits or horses that were immunized with human thymocytes. [3] By reducing the count of T cells, Thymo prevents KTRs’ white blood cells from rejecting the transplanted organs. Rabbit Thymo was approved in 2017 for KTRs’ induction therapy. Before then, Basiliximab was the only FDA approved induction agent for KTRs in the U.S. Basiliximab is a chimeric mouse-human antibody and an interleukin-2 receptor antagonist (IL2RA) agent that decreases patients’ T cell production by blocking certain receptors on T cells. On the other hand, Campath is a lab-produced humanized rat monoclonal antibody that works to deplete capable immune cells, T and B cells. [4] In terms of efficacy, outcomes, and side effects after renal transplantation, Thymo and Campath are found to be most effective at preventing rejection among high-risk kidney recipients; however, Thymo is also correlated with higher rate of infections, cancer, and lymphoproliferative disease incidents. [3, 5, 6] In contrast, Basiliximab recipients showed the lowest rate of infections and side effects. Cost-wise, Basiliximab is a more cost-effective alternative to Thymo for standard and low-risk KTRs. [3, 5] An analysis of ten randomized controlled trials (over 1200 patients included) compared the efficacy of Campath relative to IL2RAs (Basiliximab and Daclizumab) and Thymo. [4] The 2012 study found that Campath resulted in a lower rate of biopsy-proven acute rejection than the induction using IL2Ras, but there was no significant difference when compared to rabbit Thymo. The study also found no apparent difference in terms of graft loss, patient death, and new-onset diabetes mellitus among the induction agents. On the other hand, a 2019 study by Alloway et.al. examined the results of two international randomized trials (508 KTRs included) to compare the efficacy of rabbit Thymo vs. Basiliximab. [7] The study found that 1 year and 5 years after transplantation, the rate of reported treatment failures was nearly 11% lower in rabbit Thymo recipients compared to the Basiliximab recipients. Furthermore, the 10-year data of the rabbit Thymo recipients showed a 10% lower acute rejection rate than the Basiliximab recipients. One new development in renal induction therapy is the combined use of Thymo and Basiliximab. The combined therapy has been used as a feasible alternative for patients who could not take full dosage of Thymo due to various health reasons such as thrombocytopenia, leukopenia, or cytokine release syndrome. Since Basiliximab on its own was sometimes considered too weak to prevent graft failure, an induction therapy consisting of both Thymo and Basiliximab became a plausible option. A 2023 retrospective study of 80 KTRs showed that one-year graft survival rate was not significantly different between the Basiliximab recipients and the Thymo-Basiliximab combined recipients, suggesting a positive support for the dual induction therapy consisted of low-dosage Thymo and Basiliximab. [8] On the other hand, a national study published in 2021 by Lam et. al [9] concluded that patients who received the Thymo-Basiliximab combined induction therapy have an increased risk of graft loss and mortality five years after transplantation when compared to those who received Thymo-only induction therapy. This study analyzed data of over 150,000 KTRs from a national registry between 2005 and 2018. The other new trend worth noting is the exclusion of steroids from maintenance therapy. Due to their anti-inflammatory and immunosuppressive properties, steroids have historically been used to prevent acute rejection after renal surgeries. However, long-term steroid use could cause adverse side effects such as osteoporosis, cataract, and higher cardiovascular and infection risks. A 2016 study by Haller et al. found that the acute rejection risk was noticeably higher for patients who were subjected to steroid reduction or withdrawal. [10] However, a couple other studies found steroid reduction techniques to be safe and effective as steroid-based maintenance therapy, and that steroid withdrawal are especially beneficial to certain patient groups, including African American recipients, sensitized patients, and pediatric patients. [11, 12] The purpose of this study is two-fold: One is to evaluate whether the combined Thymo-Basiliximab induction therapy is as effective as other regimens (Thymo, Simulect, Campath) in preventing graft failures and patient death. The other is to examine whether the steroid-free maintenance therapy is as effective as the steroid-included maintenance therapy in graft failures and patient mortality.