What is the treatment for transplant rejection reactions?

From the Guidelines

Transplant rejection reactions are treated with a combination of immunosuppressive medications, with the most recent and highest quality study recommending a treatment approach that includes high-dose intravenous methylprednisolone, plasmapheresis, and intravenous immune globulin (IVIg) for acute rejection episodes, as outlined in the 2015 study by the American Heart Association 1. The treatment of transplant rejection reactions involves a multi-faceted approach, with the goal of preventing the immune system from attacking the transplanted organ.

• The standard treatment approach involves a combination therapy typically including calcineurin inhibitors, antimetabolites, and corticosteroids.
• For acute rejection episodes, high-dose intravenous methylprednisolone (500-1000mg daily for 3 days) is often the first-line treatment, as recommended by the American Gastroenterological Association 1.
• In steroid-resistant cases, T-cell depleting antibodies like thymoglobulin or alemtuzumab may be used, as outlined in the 2015 study by the American Heart Association 1.
• Maintenance immunosuppression typically involves tacrolimus, mycophenolate mofetil, and prednisone, with target blood levels and dosages individualized based on the type of transplant, severity of rejection, patient characteristics, and side effect profiles.
• Newer agents like belatacept, sirolimus, and everolimus may be used in specific situations, as recommended by the American Heart Association 1.
• Patients require regular monitoring of drug levels, kidney and liver function, complete blood counts, and transplant function to balance adequate immunosuppression with minimizing medication side effects and infection risks.
• Prophylactic antimicrobials are often prescribed to prevent opportunistic infections during periods of intense immunosuppression, as recommended by the American Gastroenterological Association 1. The 2015 study by the American Heart Association 1 provides the most recent and highest quality evidence for the treatment of transplant rejection reactions, and its recommendations should be prioritized in clinical practice.
• The study outlines a treatment approach that includes high-dose intravenous methylprednisolone, plasmapheresis, and IVIg for acute rejection episodes, with individualized treatment based on the type of transplant, severity of rejection, patient characteristics, and side effect profiles.
• The study also recommends regular monitoring of drug levels, kidney and liver function, complete blood counts, and transplant function to balance adequate immunosuppression with minimizing medication side effects and infection risks.

From the FDA Drug Label

The primary efficacy endpoint was the proportion of patients in each treatment group who experienced treatment failure within the first 6 months after transplantation (defined as biopsy-proven acute rejection on treatment or the occurrence of death, graft loss or early termination from the study for any reason without prior biopsy-proven rejection). Mycophenolate mofetil, when administered with antithymocyte globulin (ATGAM ® †) induction (one study) and with cyclosporine and corticosteroids (all three studies), was compared to the following three therapeutic regimens: (1) antithymocyte globulin (ATGAM ® †) induction/azathioprine/cyclosporine/corticosteroids, (2) azathioprine/cyclosporine/corticosteroids, and (3) cyclosporine/corticosteroids. Mycophenolate mofetil, in combination with corticosteroids and cyclosporine reduced (statistically significant at 0. 05 level) the incidence of treatment failure within the first 6 months following transplantation.

The treatment for transplant rejection reactions is mycophenolate mofetil in combination with corticosteroids and cyclosporine. This combination has been shown to reduce the incidence of treatment failure within the first 6 months following transplantation, as defined by biopsy-proven acute rejection on treatment or the occurrence of death, graft loss, or early termination from the study for any reason without prior biopsy-proven rejection 2.

• Key components of the treatment regimen:
  • Mycophenolate mofetil
  • Corticosteroids
  • Cyclosporine
• Alternative therapeutic regimens:
  • Antithymocyte globulin induction/azathioprine/cyclosporine/corticosteroids
  • Azathioprine/cyclosporine/corticosteroids
  • Cyclosporine/corticosteroids

From the Research

Treatment for Transplant Rejection Reactions

• The treatment for transplant rejection reactions typically involves immunosuppressive therapy to prevent the immune system from attacking the transplanted organ 3.
• Standard immunosuppressive therapy in renal transplantation consists of baseline therapy to prevent rejection and short courses of high-dose corticosteroids or monoclonal or polyclonal antibodies as treatment of ongoing rejection episodes 3.
• Triple-drug therapy with the combination of cyclosporin, corticosteroids, and azathioprine is now the most frequently used immunosuppressive drug regimen in cadaveric kidney recipients 3.
• Newer immunosuppressive agents such as tacrolimus, mycophenolate mofetil, and sirolimus have also been shown to be effective in reducing the incidence of acute rejection 3, 4, 5.
• Steroid avoidance or withdrawal has also been explored as a strategy to reduce the side effects of long-term steroid use, with some studies showing that it is feasible and safe in certain patient populations 5, 6, 7.

Immunosuppressive Regimens

• A regimen of tacrolimus-based immunosuppression with basiliximab, mycophenolate mofetil, and low-dose steroid has been shown to reduce acute rejection in kidney transplants 4.
• A comparison of steroid avoidance in tacrolimus/mycophenolate mofetil and tacrolimus/sirolimus combination in kidney transplantation monitored by surveillance biopsy found that both regimens were effective in reducing acute rejection and subclinical acute rejection 5.
• A prospective, randomized, controlled study found that a steroid-avoidance immunosuppression regimen in live-donor renal allotransplant recipients was feasible, safe, and carried fewer morbidities compared to a regimen with steroid maintenance 6.

Outcomes of Corticosteroid Withdrawal

• A meta-analysis of randomized controlled trials found that late corticosteroid withdrawal after renal transplantation in patients exposed to tacrolimus and/or mycophenolate mofetil was associated with a reduction in total cholesterol levels and improved pediatric growth outcomes, but did not reduce the risk of acute graft rejection or post-transplant diabetes mellitus 7.