Basiliximab in Steroid-Resistant Liver Rejection
Basiliximab is NOT indicated for treatment of steroid-resistant liver rejection; it is FDA-approved only for prophylaxis of acute rejection in renal transplantation and should not be used to treat established rejection episodes. 1
FDA-Approved Indication and Evidence Base
Basiliximab (Simulect®) is FDA-approved exclusively for prophylaxis of acute organ rejection in renal transplantation when used with cyclosporine and corticosteroids. 1
The FDA label explicitly states: "The efficacy of Simulect for the prophylaxis of acute rejection in recipients of other solid organ allografts has not been demonstrated." 1
Basiliximab functions as a chimeric monoclonal antibody that blocks the IL-2 receptor (CD25) on activated T lymphocytes, preventing their proliferation during the initial post-transplant period. 2
Role in Liver Transplantation (Prophylaxis Only)
While basiliximab is used off-label for induction therapy in liver transplantation, the evidence supports only its prophylactic role, not treatment of established rejection:
The 2016 EASL guidelines note that IL-2 receptor antagonists (including basiliximab) are associated with less steroid-resistant acute rejection when used as induction therapy, but this refers to prevention, not treatment of existing rejection. 2
A literature review of 18 studies showed liver transplant patients receiving IL-2R antagonists as induction experienced lower rates of steroid-resistant rejection compared to controls, but these agents were used prophylactically at transplantation, not therapeutically for established rejection. 2
Critical caveat: These agents "should always be used in combination with CNIs to avoid high incidence of acute rejection" when used prophylactically. 2
Evidence from Hematopoietic Cell Transplantation Context
The only data on basiliximab for treating steroid-refractory rejection comes from hematopoietic cell transplantation (HCT), not liver transplantation:
In a phase II trial of 23 HCT patients with steroid-refractory acute GVHD, basiliximab (20 mg IV on days 1 and 4) achieved an 83% overall response rate, but liver involvement showed the poorest response at only 14% compared to 77% for skin and 67% for GI involvement. 2
One-year treatment-related mortality was 45%, with infections occurring in 65% of patients. 2
This HCT data cannot be extrapolated to liver transplant rejection, as the pathophysiology of GVHD differs fundamentally from allograft rejection.
Appropriate Treatment for Steroid-Resistant Liver Rejection
For actual steroid-resistant acute cellular rejection in liver transplantation, evidence-based options include:
Anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) are the established agents for steroid-resistant rejection, though they carry significant infection risk. 2
Optimization of calcineurin inhibitor levels (tacrolimus preferred over cyclosporine) is first-line. 2, 3
Addition of mycophenolate mofetil to the baseline regimen can be effective. 3
For chronic rejection, mTOR inhibitors (sirolimus/everolimus) may be added, though they should be avoided early post-transplant due to hepatic artery thrombosis risk. 2, 3
Retransplantation may be necessary for advanced ductopenic rejection unresponsive to medical therapy, though rates have decreased to <2% with modern immunosuppression. 3
Clinical Bottom Line
Do not use basiliximab to treat steroid-resistant liver rejection. It lacks FDA approval, has no supporting evidence in this indication, and the only tangentially related data (from HCT GVHD) shows poor efficacy specifically for liver involvement (14% response rate). 2 Instead, optimize tacrolimus levels, add mycophenolate mofetil, or consider ATG/ALG for true steroid-resistant acute cellular rejection. 2, 3