Immunosuppressive Drug Therapy
Immunosuppression is characterized by the reduction in the effectiveness of the immune system’s response to foreign substances. This can be the result of diseases such as AIDS and cancer, or therapies including immunosuppressive drugs, radiation or splenectomy.1
Immunosuppressive drugs (ISDs) are commonly prescribed to reduce the body’s immune response for:2
- The prevention of organ or graft rejection Learn more
- The treatment of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, myasthenia gravis, noninfectious uveitis, and Crohn’s disease
- The treatment of non-autoimmune diseases such as the long-term control of allergic asthma
Immunosuppressive drugs form the mainstay of treatment following organ transplantation, ensuring long-term graft survival and improving the overall success rate of transplantation. ISD therapy is administered mainly during three phases after transplantation:
- Induction - intense immunosuppression immediately following transplantation
- Maintenance - the phase after the acclimatization of the transplanted organ in the recipient
- Reversal of established rejection3
Classification of ISDs4
The drugs commonly used to suppress the immune system are classified into several categories based on mechanism of action as shown in the table below.
| Category | Types | Example |
|---|---|---|
| Immunophilin-binding drugs | Calcineurin inhibitors | Cyclosporine A, tacrolimus |
| Non-inhibitors of calcineurin | Sirolimus | |
| Anti-metabolites | Inhibitors of de novo purine synthesis | Mycophenolic acid (MPA) Mycophenolate ofetil (MMF), azathioprine |
| Inhibitors of de novo pyramidine synthesis | Leflunomide | |
| Biologic immunosuppression | Polyclonal antibodies | Anti-thymocyte gamma globulin thymoglobulin |
| Monoclonal antibodies | Anti-CD3 monoclonal antibody (OKT3), IL-2H (humanized) | |
| Others | Deoxyspergualin, corticosteroids, fingolimod (FTY720) |
Recent Trends in Immunosuppression
Immunosuppressive therapy has changed considerably over the past few decades with the introduction of new drugs and development of different drug regimens. The changing trends for optimizing transplantation management include:
- Multi-regimen therapies
- Calcineurin inhibitor (CNI) minimization regimens
- Calcineurin inhibitor avoidance regimens
ISD Monitoring
Rejection can occur any time post transplantation, and hence the lifelong administration of ISDs is usually required. The treatment regimen necessitates the regular monitoring and regulation of ISD doses in order to prevent probable rejection events and major adverse effects associated with supratherapeutic and subtherapeutic drug levels.
Some of the common techniques adopted for therapeutic drug monitoring (TDM) include the following:
1. Trough concentration monitoring (C0): In this method, the drug level that is reached prior to the administration of the subsequent dose is measured. One of the main drawbacks of this technique is that it provides just an approximate estimate of the drug levels during the dosing interval.5 The advantage of C0 monitoring, however, is that it requires only one sample, eliminating the need for patients to wait in the hospital, clinic, or physician office for multiple samples to be drawn.