Organ transplant technology has advanced an enormous amount since the last century. The discovery and development of immunosuppressant therapy in the mid-1970s was a breakthrough that allowed for more transplants to occur, and every year since, further improvement in therapies, successful transplantation, and longevity post-transplant has followed.
Numerous challenges surround the organ transplant process, starting with the imbalance in supply and demand for organs. Approximately 107,000 individuals in the US are included on waiting lists for organs today. Deceased and living donors made under 39,000 organ transplants possible in 2020, so while the nation’s Organ Procurement and Transplantation Network
operates a successful registry for organ matching, the overall shortage leaves many waitlist patients in need. The scarcity also adds further significance to the prevention of organ rejection and fighting infection in those who can be matched with a donor organ.
All transplant patients need immunosuppressants in order to avoid transplant rejection. The drawback of weakening the immune system is the reduction in the ability to stave off opportunistic infections and disease. Multiple medications are usually prescribed to manage comorbidities, possibly for the rest of a patient’s life. Patients will receive a corticosteroid directly prior to transplantation, such as prednisone
(synthetic glucocorticoid with little mineralocorticoid activity). Glucocorticoids like prednisone are naturally occurring hormones that prevent or suppress inflammation and immune responses when administered at pharmacological doses. Transplant patients may also be given an antiproliferative agent, such as mycophenolate mofetil
, or sirolimus
, which are used as part of immunosuppressive regimens to help prevent the multiplication of immune cells. Soon after transplantation, monoclonal antibodies such as basiliximab
will likely be administered as another way to block immune cell production. Other medications given post-transplant are polyclonal antibodies, which will temporarily reduce immune system responses, thereby preventing rejection of a donor organ. The two drugs in this group are anti-thymocyte globulin (equine)
and anti-thymocyte globulin (rabbit)
. Lastly, a class of drugs known as calcineurin inhibitors is used to treat transplant rejection and for transplant rejection prophylaxis. These medicines include cyclosporine
An exciting advancement in transplant medications came earlier this year with the approval of a new indication for Prograf (tacrolimus)
. Prograf can now be used in combination with other immunosuppressant drugs to prevent organ rejection in adult and pediatric patients receiving lung transplantation. The approval is impressive both as the being for the first immunosuppressant endorsed for prevention of lung transplant rejection and because there was no prospective trial conducted using tacrolimus in donor lung recipients. Since tacrolimus has prior approvals for rejection protection in multiple other organ transplantations, the FDA was satisfied with the real-world evidence provided through an observational study demonstrating the drug’s effectiveness. Data from the federal transplant registry supplied the evidence needed in order for the FDA to make its decision.
Like all other immunosuppressive therapies, Prograf comes with the risk of increased patient susceptibility to infections. For example, lung transplant recipients have an incidence of cytomegalovirus (CMV) infection of up to 90% in those without CMV prophylaxis. This high risk of potentially deadly infection occurring makes approvals such as the recent one for Livtencity (maribavir)
breakthrough advancements. Livtencity is a novel benzimidazole riboside approved for adult and pediatric patients aged 12 years and older and who weigh at least 35kg with post-transplant CMV infection that does not respond to antiviral treatment. The drug inhibits human CMV enzyme pUL97 activity, thereby blocking replication of the virus. New therapeutic options such as Livtencity can give patients fighting infection post-transplantation a better chance for longer life.
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