Usage
- Abatacept is prescribed for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have had an insufficient response or intolerance to other disease-modifying antirheumatic drugs (DMARDs), including methotrexate (MTX) or tumor necrosis factor (TNF) blocking agents. It is also indicated for moderate to severe active polyarticular juvenile idiopathic arthritis (pJIA) in pediatric patients 2 years of age and older who have had an inadequate response to previous DMARD therapy, and for active psoriatic arthritis (PsA) in adults. Additionally, it is used for the prophylaxis of acute graft versus host disease (aGvHD) in combination with a calcineurin inhibitor and methotrexate, in adults undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.
- Pharmacological Classification: Selective costimulation modulator, Immunomodulator, Disease-modifying antirheumatic drug (DMARD), Biologic.
- Mechanism of Action: Abatacept inhibits T-cell activation by selectively binding to CD80 and CD86 on antigen-presenting cells (APCs), blocking the interaction with CD28 on T-cells. This interaction is a necessary costimulatory signal for full T-cell activation. By disrupting this signal, abatacept reduces the inflammatory response associated with RA, pJIA, and PsA.
Alternate Names
- International Nonproprietary Name (INN): Abatacept
- Brand Names: Orencia, Orencia ClickJect
How It Works
- Pharmacodynamics: Abatacept modulates the immune response by inhibiting T-cell activation, reducing inflammation, and slowing the progression of joint damage.
- Pharmacokinetics: Abatacept exhibits dose-proportional pharmacokinetics. The subcutaneous (SC) route has a bioavailability of approximately 78%. Steady state is reached in 3 months for both routes.
- Mode of Action: Abatacept binds to CD80 and CD86 on antigen-presenting cells, preventing the binding of CD28 on T-cells, which is required for their activation.
- Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Binds to CD80/86 receptors, leading to inhibition of T-cell activation.
- Elimination Pathways: Abatacept undergoes elimination via catabolism; it is not specifically cleared by renal or hepatic pathways, and not metabolized by CYP enzymes.
Dosage
Standard Dosage
Adults (RA and PsA):
- IV: Weight-based dosing: <60 kg: 500 mg; 60-100 kg: 750 mg; >100 kg: 1000 mg, infused over 30 minutes. Initial dose followed by doses at 2 and 4 weeks after the first infusion, and then every 4 weeks thereafter.
- SC: 125 mg subcutaneously once weekly, with or without an IV loading dose (same weight-based dosing as IV). If using an IV loading dose, the first SC dose should be administered within one day of the IV infusion.
Children (pJIA, ≥2 years):
- IV (≥6 years): Weight-based dosing: <75 kg: 10 mg/kg; ≥75 kg: Adult dose (not to exceed 1000 mg), infused over 30 minutes. Initial dose followed by doses at 2 and 4 weeks after the first infusion, and then every 4 weeks thereafter.
- SC (≥2 years): Weight-based dosing: 10 kg to <25 kg: 50 mg; 25 kg to <50 kg: 87.5 mg; ≥50 kg: 125 mg, subcutaneously once weekly.
Special Cases:
- Elderly Patients: No dose adjustment is required.
- Patients with Renal Impairment: No specific dose recommendations, as abatacept has not been studied in this population.
- Patients with Hepatic Dysfunction: No specific dose recommendations, as abatacept has not been studied in this population.
- Patients with Comorbid Conditions: Close monitoring and caution advised, especially with conditions predisposing to infections (e.g., diabetes, COPD).
Clinical Use Cases
Abatacept is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is used for chronic management of RA, pJIA, PsA, and prevention of aGvHD in HSCT.
Dosage Adjustments
Dose adjustments may be necessary for patients transitioning from IV to SC administration. The first SC dose should be administered instead of the next scheduled IV dose. No specific dose adjustment is recommended for elderly patients, however, caution should be used due to increased risk of infections.
Side Effects
Common Side Effects:
Upper respiratory tract infections (URTIs), headache, nausea. Injection site reactions (with SC administration).
Rare but Serious Side Effects:
Serious infections (e.g., pneumonia, sepsis), malignancy, hypersensitivity reactions (including angioedema and anaphylaxis).
Long-Term Effects:
Potential increased risk of infections with prolonged use.
Adverse Drug Reactions (ADR):
Anaphylaxis, angioedema.
Contraindications
- Severe and uncontrolled infections (sepsis, opportunistic infections).
- Hypersensitivity to abatacept or any component of the formulation.
Drug Interactions
- Clinically Significant Drug Interactions: Concomitant use with TNF inhibitors is not recommended due to increased risk of serious infections. Avoid concomitant use of other biologic DMARDs. Live vaccines should not be given concurrently or within 3 months of discontinuation. Consult drug interaction resources for a comprehensive list of potential interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (Australia); Not assigned (US FDA).
- Fetal Risks: Insufficient data available on use in pregnant women to inform drug-related risk. Abatacept may cross the placenta, potentially increasing the risk of infection in infants exposed in utero. Live vaccines are not recommended for these infants for 14 weeks following the mother’s last exposure.
- Breastfeeding: Limited information available. Abatacept is present in rat milk. Potential for serious side effects in the breastfed child. Breastfeeding is generally not recommended during treatment and for up to 14 weeks after the last dose.
Drug Profile Summary
- Mechanism of Action: Inhibits T-cell activation by binding to CD80/86.
- Side Effects: URTIs, headache, nausea, injection site reactions, serious infections, malignancy, hypersensitivity reactions.
- Contraindications: Severe infections, hypersensitivity to abatacept.
- Drug Interactions: TNF inhibitors, other biologic DMARDs, live vaccines.
- Pregnancy & Breastfeeding: Use only if clearly needed during pregnancy. Breastfeeding not recommended.
- Dosage: See detailed dosage guidelines above.
- Monitoring Parameters: Monitor for signs of infection, malignancy, hypersensitivity reactions. Periodically assess disease activity and adjust therapy as needed.
Popular Combinations
Abatacept is often used in combination with methotrexate (MTX) in patients with RA and pJIA. However, combining abatacept with other biologic DMARDs, especially TNF inhibitors, is not recommended due to increased infection risk.
Precautions
- Screen for TB, hepatitis B and C before initiating therapy.
- Monitor for signs of infection throughout treatment.
- Avoid live vaccines during treatment and for 3 months after discontinuation.
- Caution in patients with COPD, as it may worsen respiratory symptoms.
- Increased risk of perioperative infections; consider withholding abatacept prior to surgery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Abatacept?
A: The dosage depends on the indication, patient’s age and weight, and route of administration (IV or SC). Please refer to the detailed dosage guidelines provided above.
Q2: How is Abatacept administered?
A: Abatacept can be administered intravenously (IV infusion over 30 minutes) or subcutaneously (SC injection).
Q3: What are the common side effects of Abatacept?
A: Common side effects include upper respiratory tract infections, headache, and nausea. Injection site reactions may occur with SC administration.
Q4: What are the serious side effects of Abatacept?
A: Serious side effects include severe infections (e.g., pneumonia, sepsis), malignancy, and hypersensitivity reactions (including anaphylaxis and angioedema).
Q5: Can Abatacept be used during pregnancy and breastfeeding?
A: Abatacept should be used during pregnancy only if clearly needed. It is generally recommended to avoid breastfeeding during treatment and for 14 weeks after the last dose.
Q6: What are the contraindications for Abatacept?
A: Abatacept is contraindicated in patients with severe and uncontrolled infections and in those with hypersensitivity to the drug or its components.
Q7: What are the key drug interactions with Abatacept?
A: Concomitant use of TNF inhibitors is not recommended. Avoid use with other biologic DMARDs. Live vaccines should not be administered during treatment or within 3 months of discontinuation.
Q8: How does Abatacept work?
A: Abatacept inhibits T-cell activation by blocking the costimulatory signal required for their full activation. This reduces the inflammatory response associated with autoimmune diseases.
Q9: What monitoring is required for patients on Abatacept?
A: Monitor for signs of infection, malignancy, and hypersensitivity. Periodically assess disease activity and adjust treatment as needed. Before initiating therapy, screen for TB and viral hepatitis.
