Anti-thymocyte globulin (ATG)

Immunosuppression in solid organ transplantation
- Prevention of graft rejection in renal transplantation
- Treatment of steroid resistant graft rejection in renal transplantation
- Prevention of graft rejection in heart transplantation

ATG is usually used in combination with other immunosuppressive drugs

Two licensed products are available in the United States: Thymoglobulin® and Atgam®

Thymoglobulin® is licensed in the United Kingdom

Thymoglobulin® - Rabbit anti-thymocyte globulin

Intravenous infusion; 25mg per vial.
Must be diluted before IV infusion in 0.9% sodium chloride or 5% glucose – usually into 50mls.
Once diluted, use immediately
It is recommended that Thymoglobuline is administered through a 0.22 μm in-line filter.

Atgam® - Equine anti-thymocyte globulin

Intravenous (IV) infusion; 50mg of equine gamma globulin per ml.
Must be diluted before IV infusion – final concentration should not exceed 4mg/ml.
Once diluted, use immediately.
Let the drug reach room temperature before IV infusion.
It is recommended that Thymoglobuline is administered through a 0.22 μm in-line filter

Thymoglobulin®:

Do not administer if patient has a history of hypersensitivity reactions towards rabbit proteins or to excipients.

Atgam®:

Do not administer if patient has a history of hypersensitivity reactions towards equine proteins or to excipients.

In either case, do not administer if patient has a current infection as this can lead to severe health consequences.

Monitor liver function tests.
Monitor for cytomegalovirus (CMV) infection as with all immunosupressants
Monitor for symptoms of hypersensitivity reaction during IV infusion.
Monitor for symptoms of thrombocytopenia and leucopenia.
Monitor platelet and white blood cell counts.

Atgam®

There is a risk of developing Creutzfeldt-Jakob disease (CJD).
Monitor the number of rosette-forming cells (RFCs) in blood. Adjust dose accordingly - aim for a concentration of RFCs 10% of that before treatment.

Pre-administration procedures to identify possible patient hypersensitivity reactions:

Firstly, commence with a skin prick test using undiluted Atgam®.
After 10 minutes, if there is not the appearance of a wheal, proceed with an intradermal test.
For the intradermal test, inject 0.02ml of diluted Atgam® (diluted 1000 fold in 0.09% sodium chloride).
The reliability of skin testing is uncertain. And so a full dosing regimen of Atgam® should be carefully considered. ­If possible, alternative immunosuppressive treatment should be administered if positive test results arise.
Careful monitoring should be conducted on patients who have reacted positively to the skin test but are still administered Atgam®. Life support equipment should be readily available and specialist assistance should be provided in case of anaphylaxis.

Cytopenias: Thrombocytopenia, leukopenia.
Infusion reactions: Rash, chills, fever, nausea, malaise, diarrhea, dyspnea, vomiting, hypertension or hypotension. Symptoms can be minimised by administering all or some of the following drugs before IV infusion; antipyretics, corticosteroids or antihistamines.
Increased risk of infections: e.g Cytomegalovirus (CMV). Can possibly prevent this by reducing the dosage of maintenance immunosuppressive drugs.
Increased risk of malignancies: e.g Lymphoma.
Hypersensitivity reactions and anaphylaxis: Difficulty breathing, chest, back or flank pain, hypotension, skin reactions.
Increased risk of cytokine release syndrome (CRS) (Thymoglobulin®).
Serum sickness.

To reduce the risk of side effects it is recommended to administer an antihistamine and 100mg of hydrocortisone 15-60minutes prior to a full dose of ATG.

Thymoglobulin®:

Administer alongside other immunosuppressive drugs.
Slow IV infusion – minimum of 6 hours for first dose and then minimum of 4 hours for successive doses.
Administer to high flow veins to reduce the risk of thrombosis and phlebitis.

To treat acute rejection:

Dosing regimen: 1.5mg/kg once daily for 7 to 14 days.
Continue with maintenance therapy.

As an induction agent:

Licensed dosing regimen: 1-1.5mg/kg once a day for 5 to 9 days.

Continue with maintenance therapy.

Atgam®:

Administer alongside other immunosuppressive drugs.
Slow IV infusion – minimum of 4 hours. Recommended infusion time is 4-8 hours.
Administer to high flow veins to reduce the risk of thrombosis and phlebitis.

To treat acute rejection:

The first dose can be administered as soon as acute rejection has been diagnosed.
Dosing regimen: 10-15mg/kg once daily for 14 days.
Regimen can be continued if required but administer drug every other day.
Total of 21 doses over 28 days.
Continue with maintenance therapy (e.g. azathioprine).

As an induction agent:

The first dose can be administered 24 hours before or after the transplantation.
Dosing regimen: 15mg/kg 1x daily for 14 days.
After 14 days, administer 15mg/kg every other day.
Total of 21 doses over 28 days.
Continue with maintenance therapy.

Dose as in normal renal function

Avoid live vaccines for at least 6 months after treatment

There is a risk of over-immunosuppression with concomitant prescribing of standard maintenance immunosuppressive regimens

Advise patients to avoid live vaccines for at least 6 months after treatment
ATG should only be administered if the benefits of the treatment outweigh the possible harmful effects to the foetus. Pregnant women should be advised on the possible harmful effects to the foetus and the alternative treatments that are available.
Advise males and females that there could be a risk to reproductive capability when administered ATG.
Mothers should be advised on the risks associated with drug transmission via breast feeding, ideally avoid breast feeding.

Advise patients on the possible side effects during and after administration and to report any unusual symptoms.

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References:

Thymoglobulin®

https://www.drugs.com/monograph/antithymocyte-globulin-rabbit.html#unlbl-use

https://www.genzymeclinicalresearch.com/pdf/thymoglobulin_pi.pdf

Atgam®

https://www.drugs.com/monograph/antithymocyte-globulin-equine.html

https://labeling.pfizer.com/ShowLabeling.aspx?id=525

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