What is Thymoglobulin (Anti-thymocyte globulin)?

From the Guidelines

Thymoglobulin (Anti-thymocyte globulin) is a polyclonal antibody preparation used primarily in transplant medicine as an immunosuppressant, specifically indicated for the prevention and treatment of acute rejection in organ transplantation, particularly in kidney transplants, and is administered intravenously at a dose range of 1.5-10 mg/kg/day for 4-14 days. The medication works by depleting T-cells, which are key players in the immune response that leads to organ rejection 1. Healthcare providers should be aware that Thymoglobuline can cause significant immunosuppression, increasing the risk of infections, and patients require careful monitoring for cytokine release syndrome during infusion, which can cause fever, chills, and other flu-like symptoms 1. Blood counts should be regularly checked, as Thymoglobuline can cause thrombocytopenia and leukopenia, and premedication with corticosteroids, acetaminophen, and antihistamines is often recommended to reduce infusion-related reactions 1. Some studies have shown that Thymoglobuline can be used in alternative donor transplantations at different doses, with a dose range of 6–10 mg/kg for ATG (Thymoglobuline) and 20–40 mg/kg for ATG-F (Grafalon) 1. The optimal conditioning regimen for a patient should be selected based on the type and status of the disease, comorbidities, underlying conditions, and donor source, and Thymoglobuline has been shown to be most efficacious in patients with MDS with HLA-DR15 histocompatibility type, marrow hypoplasia, normal cytogenetics, low-risk disease, and evidence of a PNH clone 1.

Some key points to consider when using Thymoglobuline include:

• The dose and duration of treatment may vary depending on the specific indication and patient population
• Close monitoring of blood counts and liver function is necessary to minimize the risk of adverse events
• Premedication with corticosteroids, acetaminophen, and antihistamines may be necessary to reduce infusion-related reactions
• Thymoglobuline can cause significant immunosuppression, increasing the risk of infections, and patients should be closely monitored for signs of infection
• The medication should be used in accordance with the recommended guidelines and under the supervision of a qualified healthcare provider.

From the FDA Drug Label

THYMOGLOBULIN® (anti-thymocyte globulin [rabbit]) is a purified, pasteurized, immunoglobulin G, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes

• Thymoglobulin (Anti-thymocyte globulin) is an immunosuppressive product that contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes.
• It is a purified, pasteurized, immunoglobulin G, obtained by immunization of rabbits with human thymocytes.
• The product is used to suppress immune responses, with possible mechanisms including T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities 2

From the Research

Definition and Composition of Thymoglobulin

• Thymoglobulin, also known as Anti-thymocyte globulin (ATG), is a polyclonal antiserum that induces broad non-specific immunosuppression 3.
• It is used in haematology for severe aplastic anaemia and prophylaxis and treatment of graft-versus-host disease (GVHD) after allogeneic transplantation 3.

Forms and Efficacy of Thymoglobulin

• There are two main forms of ATG: rabbit ATG (rATG) and horse ATG (hATG) 4.
• A study found that Thymoglobulin (rATG) at a dose of 3.5 mg/kg is a viable alternative to hATG when it is not available, with similar overall response rates and overall survival at 24 months 4.
• However, another study reported that hATG was found to be superior to rATG for aplastic anaemia 3.

Pharmacokinetics and Monitoring of Thymoglobulin

• The pharmacokinetics of ATG are unclear, but a study analyzed the PK of ATG in a patient with aplastic anaemia treated with BMT from a matched unrelated donor, finding an ATG concentration on day 0 of 21.8 μg/mL and an area under the concentration-time curve (AUC) for ATG of 464 μg・day/mL 5.
• Monitoring of ATG levels can be done using total lymphocyte count or CD3 count, with a target total lymphocyte count of < 0.3 x 10(9)/l 6.
• The levels of active Thymoglobulin disappear more rapidly from the circulation than total Thymoglobulin, with only 12% of patients having detectable active Thymoglobulin by day 90 compared to 81% with detectable total Thymoglobulin 7.

Clinical Uses and Outcomes of Thymoglobulin

• Thymoglobulin is used as a first-line treatment in adult patients with aplastic anaemia, in combination with cyclosporine A 4.
• A study found that the overall response rates in patients treated with Thymoglobulin were 64.6% at 6 months and 76.4% at 12 months, with an overall survival at 24 months of 89.8% 4.
• Thymoglobulin is also used for prophylaxis and treatment of GVHD after allogeneic transplantation, with a study finding that it lessens the risk of chronic GVHD but may not improve survival 3.