Antithymocyte Globulin Equine: Immune Modulation and Therapeutic Potential at Its Finest

Overview:

Antithymocyte globulin (ATG) equine is an immune globulin or polyclonal antibody administered as an intravenous infusion in a hospital setting. This drug is made by injecting donated human white blood cells, particularly T-lymphocytes, into the horse or rabbit. The blood in the horse makes its antibodies against the injected T-lymphocytes. The formed antibodies are taken from the horse, refined, and made into the ATG equine.

ATG (equine) is used to combat the type of white blood cells known as T-lymphocytes (T-cells or thymocytes). T-lymphocytes serve as a significant part of the immune system. The T-lymphocytes might erroneously attack the bone marrow in certain blood disorders like aplastic anemia. As a result, the bone marrow does not produce adequate quantities of healthy blood cells. ATG equine prevents or slows the T-lymphocytes from invading bone marrow.

Drug Group:

Antithymocyte globulin belongs to the immune globulin form of drugs. These are drug products made up of human antibodies, especially IgG (a type of immunoglobulin). This drug group is chiefly used to strengthen and reinforce the body’s natural defense system called the immune system.

Available Doses and Dosage Forms:

The Antithymocyte globulin equine comes in an injectable solution for intravenous infusion with 50 mg/mL (milligrams per milliliter) strength.

For Patients,

What Is Aplastic Anemia?

Aplastic anemia is a rare yet severe blood disorder that results when the bone marrow cannot produce adequate new blood cells (red blood cells, white blood cells, and platelets) for the system to function normally. Bone marrow is responsible for the production of fewer red blood cells, platelets, and white blood cells. So, aplastic anemia develops from the damage to the stem cell present inside the bone marrow. This damage might be present at birth or acquired following exposure to toxic substances, radiation, certain drugs, autoimmune disorders, infections, and chemotherapy. The condition can be acute to chronic and mild to severe. Unfortunately, there are no ways to prevent this serious blood condition.

Signs and Symptoms of Aplastic Anemia:

Aplastic anemia occurs in mild to severe degrees. It can be serious, leading to potentially life-threatening complications. Moreover, it can turn out to be fatal in rare events. Aplastic anemia could present no symptoms in the majority of cases. Otherwise, it shows the following signs and symptoms.

• Shortness of breath.

• Pale skin.

• Fatigue.

• Rapid heart rate.

• Irregular heartbeat.

• Recurrent and prolonged infections.

• Easy bruising.

• Bleeding gums.

• Nasal bleeding.

• Dizziness.

• Headache.

• Fever.

• Skin rashes.

How Does Antithymocyte Globulin Equine Work?

Antithymocyte globulin (equine) is an antibody preparation based on horses or rabbits that are hyperimmunized with the human thymocytes (immune cells in the thymus). This drug is used for the prevention and treatment of acute cellular rejection following solid organ transplantation. It is also used as a therapy for acute aplastic anemia.

The drug Antithymocyte is known to cause immunosuppression. Though the appropriate mechanism of action by which this drug causes immunosuppression has not been fully determined, it can be caused by a combination of processes. The actions include T-lymphocyte (a significant part of the immune system) depletion, reduced activation of T cells, and modification of their damaging abilities. Therefore, ATG equine prevents or slows the T-lymphocytes (type of white blood cells) from attacking the bone marrow. As a result, the blood is now able to produce the adequate number of cells the system needs.

What Is the Dosage of Antithymocyte Globulin Equine?

The dosing and frequency of ATG equine differ based on the condition to be treated.

Aplastic Anemia: The recommended dosage is 10 to 20 mg/kg intravenously for eight to 14 days. Then the doctors recommend this medication if required.

Renal Allograft: The range of dosage for renal allograft is between 10 to 30 mg/kg intravenously once daily.

• Delayed Onset of Rejection: The recommended dosage is 15 mg/kg IV once daily for about 14 days. Then the doctors recommend this medication if required for another 14 days.

• Treatment of Rejection: The recommended dosage is 10 to 15 mg/kg once daily for about 14 days. Then the doctors recommend this medication if required.

Skin Allograft: The dosage varies for treatment and maintenance.

• The initial dosage recommendation is 10 mg/kg intravenously 24 hours before the first allograft.

• The maintenance dosage is 10 to 15 mg/kg once daily with some dosage modifications.

• The treatment is continued until the skin allografts cover more than 20 percent of the total body surface area (BSA).

Others:

• It is used for the management of renal allograft rejections, especially with other immunosuppressants.

• Off-label uses include bone marrow allograft.

• It is prescribed for moderate to severe aplastic anemia if bone marrow transplantation is not possible.

How Effective Is Antithymocyte Globulin Equine?

ATG is primarily indicated for immune system suppression in the case of prevention of renal transplant rejection and the management of aplastic anemia. The ATG equine, as an initial treatment, showed a significant hematologic response by three months. Immunosuppressive treatments are considered markedly effective when it incorporates a combination of ATG equine and Cyclosporine. This particular combination therapy has accounted for 60 to 80 percent of responses, with a five-year survival rate of about 75 percent.

Things to Inform the Doctor Before Taking the Drug:

The drug Antithymocyte globulin equine significantly interferes with certain other drugs and conditions. So one should inform the following things to healthcare professionals if present.

• Tell the doctor if one has or develops an undesirable reaction (allergy) to ATG equine or any other globulin immunosuppressant for formulation. Also, inform the doctor if one is allergic to other active ingredients on the prescribed list.

• Moreover, any unusual or allergic reaction to other medicines, horses, preservatives, dyes, and food should be informed priorly.

• Inform the doctor about the medical conditions and illnesses one has.

• Inform the doctor if one actively takes any type of medication. This includes prescribed medication, over-the-counter medicines, vitamins, herbal products, and nutritional supplements.

• Tell the doctor if one has any active infection, particularly viral infections like cold sores, herpes simplex virus (HSV) infection, or chickenpox.

• Inform the doctor if one has any recent vaccination or is about to take an upcoming one.

• Women who are pregnant or trying to conceive should inform the doctor about their health status.

• Inform the doctor if one is breastfeeding.

How Is Antithymocyte Globulin Equine Administered?

The doctors prescribe the appropriate dosage and frequency depending on the condition to be treated and underlying medical issues. The individuals are asked to come to the hospital or clinic for the administration of ATG equine based on the schedule.

• The drug ATG equine is meant for intravenous infusion. So, this medicine is injected into the vein only by healthcare providers in the clinic or hospital setting.

• The infusion can take about several hours. So, the healthcare providers monitor closely during the infusion.

• The most common side effect associated with ATG equine infusion is an allergic reaction. So, the healthcare provider will do a skin test before the commencement of the treatment.

• For skin tests, the healthcare provider pricks the patient’s skin with a minimal dose of ATG equine and looks for any undesirable skin reaction.

• Additional medications might be given before the infusion to prevent or reduce allergic reactions, according to the results of skin allergy tests.

• Once the infusion is initiated, the patient is watched closely for signs of allergic reaction and other unwanted side effects.

• The healthcare providers monitor and record the vital signs during the infusion. These vital signs include temperature, pulse oximetry, and blood pressure.

Points to Remember:

• ATG equine intravenous injection is given into the vein. The healthcare providers administer this infusion for several hours in a clinic or hospital setting.

• This medication is not meant for self-administration.

• This medication is only for the person the doctor prescribed. Do not share ATG equine medication with others.

What Are the Side Effects of Antithymocyte Globulin Equine?

Antithymocyte globulin equine is considered a safe and effective drug for treating aplastic anemia and kidney transplant concerns. It can cause several undesirable side effects. The common side of ATG equine includes the following, which could resolve on their own even without medical attention. But, one must bring to the doctor's notice if any of the following symptoms are distressing.

• Fever.

• Hives.

• Chills.

• Itching.

• Chest or back pain.

• Joint pain.

• Diarrhea.

• Headache.

• Nausea.

• Vomiting.

• Dizziness.

• Night sweats.

• Breathlessness.

• Low blood pressure.

• Pain at the site of infusion.

In addition, ATG equine can cause several serious side effects. In such a case, one should seek medical attention straight away.

• Chest pain.

• Back pain.

• Fast heartbeat.

• Easy bruising.

• Coughing up blood.

• Vomit looks like coffee grounds.

• Seizure.

• Fever.

• Swelling of the face, throat, and lips.

• Lightheadedness.

• Abnormal bleeding.

• Red and purple pinpoint spots appear under the skin.

• Difficulty breathing.

• Skin sores.

• Rash.

• Itching.

• Swollen glands.

• Muscle and joint pain.

• Tiredness.

• Irritability.

Serious Side Effects:

Serious side effects are sometimes associated with ATG equine treatment. So, one should seek emergency care or medical support at the earliest if one experiences the following serious effects.

• Eye Problems: Blurred vision, eye pain, tunnel vision, sudden vision impairment, swelling of the eye, and halos around the lights.

• Heart Concerns: Abnormal and pounding heartbeats, breathlessness, flickering in the chest, lightheadedness, dizziness, and passing out feelings.

• Others: Confusion, severe headaches, arm weakness, slurred speech, walking difficulty, unsteady gait, stiffened muscles, lack of coordination, tremors, high-grade fever, and excessive sweating.

Dietary Considerations:

One can follow the usual routine diet until the healthcare provider suggests any restrictions. But, following a well-balanced nutritious diet is considered soundest for any health concern. People with aplastic anemia can consider taking food sources rich in iron. The food sources include eggs, spinach, sweet potato, dark greens, leafy vegetables, and meat.

Missed Dose:

Missed doses cannot happen with ATG equine since it is given in the hospital setting. But, call and discuss with the doctor if one missed going for the appointment or scheduled dose. The doctors might reschedule for the missed dose.

Overdose:

Overdose of ATG equine medication is less likely to occur since it is typically given in hospital settings. One should reach out to the emergency department or medical helpline for any serious concerns.

For Doctors,

Clinical Data of Antithymocyte Globulin Equine

Drug Name: Antithymocyte globulin equine.

Generic Name: Antithymocyte globulin equine.

Other Names: Antithymocyte globulin (equine), ATG equine, eATG, Antithymocyte globulins equine, and Equine thymocyte immune globulin.

Route of Administration: Intravenous (IV) Infusion.

Indication:

Antithymocyteglobulin equine is chiefly indicated for treating aplastic anemia and preventing renal transplantation rejection.

Associated Conditions:

• Heart transplant rejection.

• Graft versus host disease.

• Kidney transplant rejection.

• Lung transplant rejection.

• Moderate aplastic anemia.

• Severe spastic anemia.

• Myelodysplastic syndrome.

What Are the Pharmacological Aspects of Antithymocyte Globulin Equine?

Mechanism of Action:

ATG (equine) comprises antibodies that chiefly bind to the wide range of proteins on the surface of lymphocytes. Moreover, ATG equine markedly binds to platelets, granulocytes, bone marrow cells, and related cells.

The mechanism of action of ATG equine has not been established and specified. The clinical data represent that the mechanism of action of ATG equine is the depletion of circulating lymphocytes, particularly T lymphocytes. Here, lymphocyte depletion might be caused due to activation-stimulated apoptosis and aggregate-dependent lysis. Immunosuppression takes place, which could be facilitated by the binding of antibodies to lymphocytes, resulting in partial activation and stimulation of T lymphocytes.

The mechanism of ATG equine for the treatment of aplastic anemia contributes to its action of immunosuppression. Moreover, ATG equine provokes and facilitates the growth of hematopoietic stem cells. In addition, it precipitates the release of hematopoietic growth factors like granulocyte macrophage stimulating components and interleukin-3.

Absorption

Onset:

• Following intravenous (IV) administration of ATG equine, an acute reduction of rosette-forming cells (RFC) concentration occurs in the peripheral blood vessels.

• In contrast, RFCs could be recovered to the usual concentration following drug discontinuance. But, recovery of RFC levels depends on the duration of treatment and the individual’s catabolic rate.

Plasma Concentrations:

• Following intravenous (IV) administration of ATG equine, peak plasma concentrations of immunoglobulin G (IgG) equine differ depending on the individual’s potency to catabolize foreign IgG.

• So, the mean plasma concentration of IgG equine is reported to be about approximately around 737 mcg/mL following ATG equine IV infusion of dosage 10 mg/kg daily for five days.

Distribution

• The mean peak value in about 27 renal transplant patients during ATG equine infusion of 10 to 15 mg/kg/day was estimated to be nearly around 727 mg/mL.

Elimination

• The estimated half-life of equine immunoglobulin following an ATG equine infusion accounted for 5.7 (greater than or less than 3.0) days among a group of participants.

• So, the range for the half-life of ATG equine was about 1.5 to 13 days.

Contraindications:

• Hypersensitivity: Do not administer ATG equine to an individual who has ever had an anaphylactic or severe systemic reaction to ATG equine or other equine gamma globulin formulation.

Storage and Handling of Antithymocyte Globulin Equine:

• Store the ATG equine drug product at a temperature between two and eight degree Celsius.

• Keep the ampoules of ATG equine in the outer carton for protection from light.

• Consider the incompatibilities and shelf life for the storage of diluted solutions.

Adverse Events of Antithymocyte Globulin Equine

General:

The following adverse reactions are most frequently reported in greater than ten percent of people taking ATG equine treatment.

• Leukopenia.

• Thrombocytopenia.

• Rash.

• Arthralgia.

• Chills.

• Pyrexia.

• Systemic infection.

• Dermatological reactions

One to ten percent of cases were found to have the following adverse reactions.

• Headache.

• Arthralgia, hypotension, clotted arteriovenous (AV) fistula, and peripheral thrombophlebitis.

• Nausea, diarrhea, vomiting, and stomatitis.

• Night sweats.

• Pain at the site of infusion.

• Dyspnea.

• Chest or back pain.

In addition, the following group adverse events are found to occur in less than one percent of cases.

• Tachycardia, edema, hypertension, pulmonary edema.

• Wound dehiscence, toxic epidermal necrolysis.

• Malaise, dizziness, seizures, paresthesia, weakness, and faintness.

• Myalgia.

• Hiccoughs, iliac vein obstruction, and pain in the epigastric region.

• Anaphylaxis, laryngospasm, and hyperglycemia.

• Localized infection, serum sickness, herpes simplex reactivation, and systemic infection.

• Renal artery thrombosis.

Aplastic Anemia

The adverse reactions sometimes occur specific to the conditions to be treated. The following drug reactions are common in people undergoing ATG equine treatment for aplastic anemia.

Greater Than Ten Percent:

• Chills.

• Arthralgia.

• Headaches.

Five to Ten Percent:

• Chest pain.

• Myalgia.

• Phlebitis.

• Nausea.

Less Than Five Percent:

• Diarrhea, vomiting.

• Proteinuria.

• Lethargy, seizures, agitation.

• Anaphylactic reactions.

• Respiratory distress.

• Diaphoresis.

• Bilateral pleural effusion, edema, congestive heart failure, hypotension, and cardiac abnormalities.

Post-Marketing Experience:

• Serum sickness.

Cautions for Antithymocyte Globulin Equine:

• Consider testing for allergic response before the initiation of treatment. Intradermal injection of ATG equine can be administered for allergy testing.

• People with aplastic anemia might require prophylactic platelet transfusion.

• Consider discontinuation of treatment if anaphylactic results. Anaphylaxis could result in unremitting leukopenia and thrombocytopenia.

• Monitor the patients conscientiously for any undesirable reactions when decreasing or modifying the dosage of immunosuppressants and corticosteroids.

Significant Warning:

Only physicians trained and experienced in immunosuppressive treatment for renal transplant recipients should prescribe the ATG equine. Moreover, the patients should receive ATG equine administration in hospital settings equipped with facilities, supportive medical measures, and laboratories. Watch the patients carefully for adverse events during and after the course of treatment. When any adverse event is detected, treatment of them should be initiated commensurate with the appropriate guidelines.

What Are the Warnings and Precautions for Antithymocyte Globulin Equine?

• General: As ATG equine solution is an immunosuppressive agent commonly used with anti-metabolites and corticosteroids, monitor the patients conscientiously for signs of thrombocytopenia, leukopenia, and concurrent infections.

• Traceability: Generally, the name and batch number of the drug product should be recorded for the improvement of traceability. The potency and activity of ATG equine might vary from individual to individual. The dilution of ATG equine is not usually recommended with the Dextrose injection since decreased salt level might lead to precipitate formation. The co-administration of highly acidic solution is also not recommended due to potential physical instability.

• Anaphylaxis and Skin Testing: DIscontinuation of ATG equine treatment is recommended in case of the occurrence of anaphylaxis. Skin treatment is significantly recommended before the commencement of ATG equine treatment for those individuals suspected of a higher risk of systemic reactions.

• Immune-Mediated Reactions: The clinical findings show some reports of severe immune-mediated reactions with ATG equine treatment at rare events. Moreover, clinical signs in association with serum sickness, anaphylaxis, and other infusion-associated reactions have also been reported. There is also evidence of the potential occurrence of cytokine request syndrome based on the mechanism of action of ATG equine. Severe systemic reactions might occur, preventing the supplemental infusion of ATG equine. These reactions include dyspnea, hypotension, rash, tachycardia, and anaphylaxis.

• Infections: This drug product might possess a risk of transmitting infectious agents causing viral diseases and Creutzfeldt-Jakob disease (CJD) since ATG equine is made with human blood components and equine. In addition, opportunistic bacterial and fungal infections are common because of the immunosuppressive nature of ATG equine. The clinical findings also report the occurrence of sepsis. There is also a greater risk of viral reactivation, like Epstein-Barr virus (EBV) infection, cytomegalovirus (CMV) infection, and Herpes simplex virus (HSV) infection. So, monitor the patients closely for any concurrent infections. A research study suggests that reducing the dosage of concomitant immunosuppressive agents could reduce the risk of infections. Consider initiation of appropriate prompt treatment of resulting infection. The physicians should decide the continuation or discontinuation of ATG equine treatment considering the clinical circumstances and directions.

• Thrombocytopenia and Neutropenia: The clinical findings say that ATG equine treatment might exacerbate the existing neutropenia and thrombocytopenia. Discontinuation of treatment should be considered in case of severe unremitting leukopenia, and thrombocytopenia occurs.

• Renal and Liver Function Tests: Abnormal results of liver function (alkaline phosphatase, serum glutamic-oxaloacetic transaminase, and serum glutamate pyruvate transaminase) and renal function ( serum creatinine level) have been reported in people with aplastic anemia and hematologic irregularities who receive ATG equine treatment. Moreover, clinical and laboratory results of serum sickness have been reported in most cases. So, consider monitoring the renal and liver function tests periodically.

• Concomitant Administration of Vaccines: The safety and efficacy profile of immunized vaccines with the ATG equine treatment has not been determined. Nevertheless, vaccination is not generally recommended in tandem with ATG equine therapy since it reduces the efficacy of the vaccine. Determine and give the prescription information regarding the appropriate vaccination intervals with respect to the immunosuppressive treatment.

Special Considerations:

• Pediatric Population: The study and experience of ATG equine in the pediatric population with renal allograft transplantation are limited. So, ATG equine is generally administered safely at decreased dosage to children with aplastic anemia and renal allograft transplantation.

• Elderly Population: The clinical findings have not observed any significant difference between the younger and elderly patients when treated with ATG equine.

• Pregnancy: Animal studies of ATG equine showed reproductive toxicity. But these effects are not regarded as relevant to humans. There are inadequate and unreliable studies showing the safety and efficacy profile of ATG equine in pregnant women. So, consider whether the potential benefit to the pregnant woman alleges the possible risk to the fetus before the usage.

• Breastfeeding: The studies do not signify whether ATG equine is excreted in human milk. Generally, many drugs are excreted through human milk, so consider either discontinuation of the drug or discontinuation of breastfeeding.