What is the typical regimen for immunosuppression?

Standard Immunosuppression Regimens in Transplantation and Autoimmune Disease

The typical immunosuppression regimen consists of a calcineurin inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate mofetil/mycophenolic acid), and corticosteroids, with specific modifications based on the underlying condition and transplant type.

Core Immunosuppression Components

Triple Therapy Approach

The cornerstone of immunosuppression in solid organ transplantation includes:

1. Calcineurin Inhibitor (CNI)

   • Tacrolimus (preferred in most centers) with target trough levels of 4-6 ng/ml 1
   • Cyclosporine A with target trough levels of 60-100 ng/ml 1

2. Antiproliferative Agent

   • Mycophenolate mofetil (MMF) 1-2 g/day or mycophenolic acid 720-1440 mg/day 1
   • Alternative: Azathioprine 1.5-2.0 mg/kg/day 1

3. Corticosteroids

   • Prednisone tapered down to <5-7.5 mg/day for maintenance 1

Induction Therapy

• Basiliximab is commonly used for induction in autoimmune liver diseases including PSC 1
• Anti-thymocyte globulin may be used in high-risk transplants
• Induction therapy is now used in >90% of kidney transplants and >50% of other solid organ transplants 2

Disease-Specific Considerations

Solid Organ Transplantation

• Liver Transplant: MMF 1.5 g twice daily or azathioprine 1-2 mg/kg/day with cyclosporine and corticosteroids 3
• Cardiac Transplant: MMF 1.5 g twice daily with cyclosporine and corticosteroids 3
• Kidney Transplant: Similar regimen with potential for steroid minimization

Autoimmune Conditions

Lupus Nephritis

For Class III and IV lupus nephritis maintenance therapy:

• First choice: Mycophenolic acid analogs (MMF 1-2 g/day or mycophenolic acid 720-1440 mg/day) 1
• Alternative options:
  • Azathioprine 1.5-2.0 mg/kg/day
  • Tacrolimus (trough ~4-6 ng/ml) or cyclosporine A (trough ~60-100 ng/ml)
  • Low-dose prednisone (<5-7.5 mg/day)

Sjögren's Syndrome (severe systemic disease)

• B-cell targeted therapies like rituximab may be considered 1
• For refractory cases: belimumab or abatacept 1

Monitoring Requirements

1. Therapeutic Drug Monitoring

   • Regular blood level monitoring for calcineurin inhibitors and mTOR inhibitors
   • Tacrolimus trough levels: 4-6 ng/ml 1
   • Cyclosporine trough levels: 60-100 ng/ml 1

2. Laboratory Monitoring

   • Complete blood count
   • Comprehensive metabolic panel
   • Drug levels
   • Disease-specific markers

3. Infection Screening

   • Tuberculosis testing before biologics 4
   • Consider PJP prophylaxis for prednisone courses >4 weeks 5

Special Considerations

Pediatric Patients

• Similar regimens to adults but with dose adjustments
• Consider growth, fertility, and psychosocial factors 1
• May favor IV medications for adherence concerns 1

Pregnancy

• Avoid mycophenolate acid analogs during pregnancy and breastfeeding 1
• Hydroxychloroquine, tacrolimus, low-dose azathioprine, and prednisone have limited transfer into breast milk and are considered safer options 1
• Belimumab is labeled as category C and cannot be recommended for use in pregnancy 1

Immunosuppression Duration

• For lupus nephritis, total duration (initial plus maintenance) should not be less than 36 months for patients who achieve complete kidney response 1
• Consider glucocorticoid discontinuation after patients maintain complete clinical response for about a year 1

Common Pitfalls and Complications

1. Infection Risk

   • Increased susceptibility to opportunistic infections
   • Consider prophylaxis for high-risk patients (PJP, CMV)

2. Medication Interactions

   • Many immunosuppressants have significant drug interactions
   • Monitor levels closely when starting or stopping other medications

3. Metabolic Complications

   • Monitor for hyperglycemia, especially with corticosteroids
   • Consider calcium/vitamin D supplementation and gastric protection for long-term steroid use 5

4. Malignancy Risk

   • Increased risk of certain malignancies with long-term immunosuppression
   • Regular cancer screening based on risk factors

By following these evidence-based regimens and monitoring protocols, clinicians can optimize immunosuppression while minimizing complications in patients requiring these therapies.