What are the indications and dosing regimens for rabbit anti-thymocyte globulin (rATG)?

Indications and Dosing Regimens for Rabbit Anti-Thymocyte Globulin (rATG)

Rabbit anti-thymocyte globulin (rATG) is FDA-approved for the treatment of renal transplant rejection, while being commonly used off-label for other transplant-related indications including induction therapy and treatment of rejection in various organ transplants. 1

FDA-Approved Indications

• Treatment of renal transplant rejection 1

Common Off-Label Indications

• Induction therapy in high-risk kidney transplant recipients 2
• Prophylaxis of renal transplant rejection 2
• Treatment and prophylaxis of lung transplant rejection 1
• Treatment of cardiac transplant rejection, particularly antibody-mediated rejection (AMR) 1
• Treatment of severe aplastic anemia (though equine ATG is considered superior for this indication) 3
• Prophylaxis and treatment of graft-versus-host disease (GVHD) after allogeneic transplantation 3

Dosing Regimens

For Renal Transplant Rejection Treatment (FDA-approved)

• Standard dosing: 1.5 mg/kg per day for 7-14 days 2
• Reduced dosing protocols:
  • 1.5 mg/kg per day for 3-4 doses in high-risk kidney transplant recipients (showing excellent protection against rejection) 4
  • 0.5 mg/kg per day plus basiliximab (20 mg 4 days apart) in high-risk kidney transplant recipients 5

For Induction Therapy in Transplantation

• Standard dosing: 1.5-2 mg/kg per day for 3-7 days 2, 4
• For cardiac transplant antibody-mediated rejection:
  • University of Utah protocol: rATG (dosage not specified) for pAMR3 with hemodynamic compromise 1
  • Cedars-Sinai protocol: rATG (dosage not specified) followed by additional therapies 1

For Pediatric Heart Transplant Recipients

• St. Louis Children's Hospital protocol: Thymoglobulin 1.5 mg/kg IV daily for 5-7 days 1

Administration Guidelines

• Initial dose should be given over at least 6 hours, with subsequent doses potentially given over 4 hours if administered through a central line 1
• Can be administered through peripheral lines with appropriate premedication 6
• For peripheral administration, add 1,000 units of heparin and 20 mg of hydrocortisone to reduce thrombosis and local tissue reaction 6

Monitoring Recommendations

• Monitor for infusion reactions during administration (pulmonary edema, systemic inflammatory response syndrome) 1
• Daily CBC and hepatic/renal function tests during initiation of therapy 1
• Adjust doses based on:
  • Suppression of sheep erythrocyte rosette levels of circulating mononucleated cells to <10% 1
  • Maintaining CD3 counts <20/mL and CD2 counts <50/mL 1
• Consider laboratory evaluation for host antibodies before reinstitution of therapy in previously exposed patients 1

Adverse Effects to Monitor

• Common reactions: fever, hyperkalemia, hypertension, CMV infection, leukopenia, peripheral edema, sepsis syndrome, shivering, tachyarrhythmia, and thrombocytopenia 1
• Infusion-related: injection site reactions, skin rash, pruritus 1
• Gastrointestinal: nausea and abdominal pain (in approximately one-third of patients) 1
• Respiratory: dyspnea (in one-fourth of patients), though ARDS is much less common 1
• Immunologic: antibodies to rabbit ATG develop in virtually all patients and may limit efficacy over time 1
• Long-term: potential increased risk for malignancies, including non-Hodgkin's lymphoma 1

Important Considerations and Precautions

• rATG is almost always used in combination with other immunosuppressive agents 1
• Prophylaxis against opportunistic infections is essential due to increased risk of bacterial, fungal, and viral infections 1
• Pregnancy classification: Category C (use only if clearly necessary) 1
• Not recommended during breastfeeding due to insufficient safety data 1
• rATG may interfere with laboratory testing for blood cross-match or panel-reactive antibody cytotoxicity assays 1
• Rabbit antibody-based serum immunoassay results may be unreliable during rATG therapy 1

Clinical Pearls

• Lower doses of rATG (1.5 mg/kg for 3-4 doses) may provide effective rejection prevention with fewer side effects in high-risk kidney transplant recipients 4
• Combining low-dose rATG with basiliximab may achieve similar antirejection activity as standard-dose rATG but with better safety profile and lower costs 5
• Outpatient administration of rATG is possible with appropriate monitoring and precautions 6
• For severe aplastic anemia, equine ATG has been found to be superior to rabbit ATG 3