2023-Costimulatory Blockade and Solid Organ Transplantation
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2023-Costimulatory Blockade and Solid Organ Transplantation
Belatacept is the first costimulatory blockade agent clinically approved for transplant immunosuppression.
Although more than 10 years of study have demonstrated that belatacept offers superior long-term renal
allograft and patient survival compared to conventional calcineurin inhibitor (CNI)-based immunosuppression
regimens, the clinical adoption of belatacept has continued to lag because of concerns of an early
risk of acute cellular rejection (ACR) and various logistical barriers to its administration. In this review, the
history of the clinical development of belatacept is examined, along with the findings of the seminal
BENEFIT and BENEFIT-EXT trials culminating in the clinical approval of belatacept. Recent efforts to
incorporate belatacept into novel CNI-free immunosuppression regimens are reviewed, as well as the
experience of the Emory Transplant Center in using a tapered course of low-dose tacrolimus in belatacepttreated
renal allograft patients to garner the long-term outcome benefits of belatacept without the shortterm
increased risks of ACR. Potential avenues to increase the clinical adoption of belatacept in the future
are explored, including surmounting the logistical barriers of belatacept administration through subcutaneous
administration or more infrequent belatacept dosing. In addition, belatacept conversion strategies
and potential expanded clinical indications of belatacept are discussed for pediatric transplant recipients,
extrarenal transplant recipients, treatment of antibody-mediated rejection (AMR), and in patients with
failed renal allografts. Finally, we discuss the novel immunosuppressive drugs currently in the development
pipeline that may aid in the expansion of costimulation blockade utilization.
Belatacept is the first costimulatory blockade agent clinically approved for transplant immunosuppression.
Although more than 10 years of study have demonstrated that belatacept offers superior long-term renal
allograft and patient survival compared to conventional calcineurin inhibitor (CNI)-based immunosuppression
regimens, the clinical adoption of belatacept has continued to lag because of concerns of an early
risk of acute cellular rejection (ACR) and various logistical barriers to its administration. In this review, the
history of the clinical development of belatacept is examined, along with the findings of the seminal
BENEFIT and BENEFIT-EXT trials culminating in the clinical approval of belatacept. Recent efforts to
incorporate belatacept into novel CNI-free immunosuppression regimens are reviewed, as well as the
experience of the Emory Transplant Center in using a tapered course of low-dose tacrolimus in belatacepttreated
renal allograft patients to garner the long-term outcome benefits of belatacept without the shortterm
increased risks of ACR. Potential avenues to increase the clinical adoption of belatacept in the future
are explored, including surmounting the logistical barriers of belatacept administration through subcutaneous
administration or more infrequent belatacept dosing. In addition, belatacept conversion strategies
and potential expanded clinical indications of belatacept are discussed for pediatric transplant recipients,
extrarenal transplant recipients, treatment of antibody-mediated rejection (AMR), and in patients with
failed renal allografts. Finally, we discuss the novel immunosuppressive drugs currently in the development
pipeline that may aid in the expansion of costimulation blockade utilization.
