Will I ever come off my immunosuppressive drugs?

Much of the success of organ transplantation can be attributed to improvements in the immunosuppressive drugs prescribed after the surgery. When the only drugs available were prednisone and azathioprine, the rejection rates and risk of graft loss were very high. Long-term survival was unusual. With the introduction of cyclosporine, however, patient survival increased almost immediately. The availability of even more drugs has since expanded the choices for safe and effective immunosuppression. Unfortunately, current immunosuppressive medications have a number of undesirable side effects (see Question 93).

Now that rejection has become a rare and controllable phenomenon, researchers are trying to determine the lowest amount of immunosuppression to prevent rejection and graft loss while at the same time minimizing the drugs’ side effects. The advent of powerful primary agents, such as tacrolimus and sirolimus, has allowed us to decrease the overall number of drugs needed in one individual for adequate immunosuppression. The agent most commonly targeted for reduction has been prednisone—the drug with the most frequent and problematic side effects. The reduction in the use of prednisone has decreased the frequency of elevated blood sugars, osteoporosis, weight gain, and edema after transplantation. Many patients with no prior episodes of acute or chronic rejection, adequate kidney function, and acceptable liver and heart function tests are able to stop taking prednisone altogether. With the addition of mycophenolate to the primary agent, even patients with a history of mild rejection may be candidates to stop prednisone therapy.

A small number of reports from transplant centers have indicated that all immunosuppressive drugs may be stopped in a select group of transplant recipients. These reports emphasize the “success stories” and deemphasize the failures and their outcomes—rejection, graft loss, retransplantation, or death. The difficulty arises in choosing the appropriate patient for total drug withdrawal. At this time we do not have any blood tests or markers that can reliably identify the best patients for removal of immunosuppression. Because the risks are so high (for example, graft loss), most transplant programs do not entertain the possibility of total immunosuppression withdrawal.