Influence of Induction Therapy Using Basiliximab With Delayed Tacrolimus Administration in Heart Transplant Recipients　― Comparison With Standard Tacrolimus-Based Triple Immunosuppression ―

Abstract

acute cellular rejection (ACR), antibody-mediated rejection (AMR), and infections remains challenging. 1 Risk factors for poor clinical prognosis or difficulties for their management by healthcare practitioners for patients necessitate alternative immunosuppression strategies. 1 Induction T riple immunosuppressive therapy including calcineurin inhibitors (CNIs), mycophenolate mofetil (MMF), and steroids, has substantially improved outcomes for heart transplant (HTx) recipients. Nevertheless, the management of CNI-related nephrotoxicity, fatal

Role of the Transplant Pharmacist

“…In such a patient, the introduction of induction therapy using basiliximab as well as two-week delayed start of administration of TAC is to be considered. To date, in our institute, the effect of induction therapy using basiliximab with delayed TAC administration on the clinical prognosis of HTRs has been verified as compared with that of a standard TAC-based triple immunosuppression therapy [23]. The former therapy might be feasible and safe for HTRs fulfilling certain inclusion criteria including renal function, sensitization for anti-human leukocyte antigen (HLA) antibody, and HTR-and donor-related risk factors, although a comprehensive evaluation of the clinical necessity of basiliximab-based induction therapy is necessary (see [23] for more detailed inclusion criteria).…”

“…Basiliximab is not approved for the treatment of HTx in Japan, but a few reports have described the use of basiliximab as beneficial after HTx [21,22]. Therefore, we usually prepare protocols in case we might use basiliximab for HTRs [23]. The protocol prepared for antibacterial and immunosuppressive therapies created by pharmacists based on this information is shared with cardiac surgeons, cardiologists, and RTCs after approval by the physician in charge.…”

Induction Therapy in the Current Immunosuppressive Therapy

“…In the current clinical situation, the improvement and establishment of new maintenance immunosuppression agents such as tacrolimus replaced cyclosporine and mycophenolate mofetil replaced azathioprine have significantly reduced risk of acute T-cell mediated rejection in acute phase post-HTx, which may lead that previously observed benefits of induction therapy tend to decrease overtime. Thus, although the clinical need of induction therapy to suppress T-cell mediated rejection may be decreasing, younger patients, multiparous women, African Americans, patients with longer term ventricular assist device, [16] and patients with long ischemic time [17] may be still good indication for the induction therapy in HTx. On the other hand, long awaiting time for HTx due to the severe donor shortage and increasing in the implantation of left ventricular assist device pre-HTx have increased risk of sensitization and pre-existing renal dysfunction before HTx.…”

“…And induction therapy may be generally used in combination with desensitization therapy, not induction therapy alone [3,5]. Patients with pre-existing renal dysfunction may still be the best indication of induction therapy in the current clinical situation [17][18][19][20].…”

“…Furthermore, most of the studies to date have been in HTx recipients who received cyclosporine rather than tacrolimus for primary immunosuppression, with limited evidence in the new immunosuppression era. Watanabe et al in HTx recipients receiving tacrolimus showed that basiliximab-based induction immunosuppressive therapy might suppress mild acute cellular rejection, and improve renal function in recipients with deteriorated renal function, and resulting in the its non-inferior outcome as compared to no-induction group even in recipients with any comorbidity [17].…”