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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.
 

Need for ISD Monitoring
Need for ISD Monitoring

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.
 

Blood Levels Vs Target Tissue Exposure
Blood Levels Vs Target Tissue Exposure

2. Area under the curve (AUC) monitoring: AUC overcame the limitations of trough monitoring and evolved as a superior technique for TDM, with benefits such as the following:

  • Provides a more accurate measure of the extent to which the body is exposed to the immunosuppressive drug
  • Predicts the concentration of a drug across the entire dose interval, traditionally with serial samples (8-12) drawn over 12 hours5
  • Pharmacokinetic profiles such as half-life, volume of distribution, and clearance can be calculated for effectively managing the administration of the drugs

The major drawback of AUC monitoring is that it is expensive and requires the patient to spend long hours in the hospital.

3. Abbreviated area under the curve monitoring: Abbreviated AUC is a limited sampling (2-4) strategy over the dosing interval, making it more convenient and economical compared to the standard AUC monitoring.5

4. C2 monitoring: The C2 monitoring strategy further limits the number of samples to one, which is collected 2 hours following the administration of the drug. The dosing and sampling time play a vital role in accurately measuring the drug levels since it is a single sampling approach. C2 monitoring is primarily used to monitor cyclosporine A levels.


Advantages of Effective ISD Monitoring

  • Decreases incidence and severity of the rejection episodes and lowers side effects
  • Improves treatment outcome
  • Optimizes patient care and enhances quality of life
  • Reduces cost

Enduring Expertise for Your Immunosuppressant Drug Testing Needs
With recognized drug testing expertise, Siemens Healthcare Diagnostics offers a comprehensive and expanding menu of tests across multiple instrument solutions to meet the immunosuppressant drug (ISD) testing needs of customers in any setting.

Learn more about our complete menu of ISD assays

References
1. National Cancer Institute. Immunosuppression. Link. Accessed Feb 2009.
2. Dreyer MS. Pharmacology for Nurses and Other Health Workers. Pearson South Africa. 2007:197. Link
3. Halloran PF. Immunosuppressive drugs for kidney transplantation. N Engl J Med. 2004;351:2715-29. Link
4. Brunicardi FC. Schwartz’s Manual of Surgery. McGraw Hill Professional. 2006:218-219. Link
5. Norman DJ. Primer on Transplantation. Blackwell Publishing. 2001:84. Link