Etanercept

Introduction to Etanercept

Etanercept is a biologic disease-modifying antirheumatic drug (DMARD) that belongs to the class of tumor necrosis factor (TNF) inhibitors. It was first approved by the FDA in 1998 for the treatment of rheumatoid arthritis and has since gained approval for several other inflammatory conditions, including some pediatric indications. Etanercept is a fusion protein consisting of the extracellular ligand-binding portion of the human TNF receptor linked to the Fc portion of human IgG1.

Mechanism of Action

Etanercept works by binding to and inhibiting the activity of tumor necrosis factor (TNF), a pro-inflammatory cytokine that plays a crucial role in various inflammatory and autoimmune conditions. The mechanism of action involves:

  • Binding to soluble TNF-α and TNF-β with high affinity, preventing them from interacting with cell surface TNF receptors
  • Competitively inhibiting the binding of TNF to its cell surface receptors, thereby reducing TNF-mediated cellular responses
  • Modulating biological responses induced or regulated by TNF, including expression of adhesion molecules, serum levels of cytokines, and matrix metalloproteinase-3 (stromelysin)

By inhibiting TNF, etanercept helps to reduce inflammation, pain, and joint damage in various inflammatory conditions. Its effects are reversible upon discontinuation of the drug.

Indications

Etanercept is FDA-approved for the following indications:

  • Rheumatoid Arthritis (RA): Reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active RA
  • Polyarticular Juvenile Idiopathic Arthritis (JIA): In patients aged 2 and older
  • Psoriatic Arthritis (PsA): Reducing signs and symptoms, inhibiting the progression of structural damage of active arthritis, and improving physical function in patients with PsA
  • Ankylosing Spondylitis (AS)
  • Plaque Psoriasis: In patients 4 years or older with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy

Of particular interest to pediatricians are the indications for polyarticular JIA and pediatric plaque psoriasis, which make etanercept one of the few biologic agents with specific pediatric indications.

Dosage and Administration

Etanercept is administered by subcutaneous injection. The dosage varies depending on the indication and the patient's age and weight:

  • Adult Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis: 50 mg once weekly
  • Adult Plaque Psoriasis: Starting dose of 50 mg twice weekly for 3 months, followed by 50 mg once weekly
  • Polyarticular Juvenile Idiopathic Arthritis (JIA):
    • Patients 2-17 years weighing ≥ 63 kg: 50 mg once weekly
    • Patients 2-17 years weighing < 63 kg: 0.8 mg/kg once weekly (maximum 50 mg per week)
  • Pediatric Plaque Psoriasis:
    • Patients 4-17 years weighing ≥ 63 kg: 50 mg once weekly
    • Patients 4-17 years weighing < 63 kg: 0.8 mg/kg once weekly (maximum 50 mg per week)

Etanercept is available in pre-filled syringes, auto-injectors, and multi-dose vials. Proper training in injection technique is essential for patients or caregivers administering the medication at home.

Adverse Effects

Common adverse effects of etanercept include:

  • Injection site reactions (erythema, itching, pain, swelling)
  • Upper respiratory infections
  • Headache
  • Rhinitis
  • Dizziness
  • Pharyngitis
  • Cough
  • Asthenia

More serious adverse effects, although less common, may include:

  • Serious infections, including tuberculosis and invasive fungal infections
  • Malignancies, particularly lymphoma
  • Demyelinating disorders
  • Congestive heart failure
  • Lupus-like syndrome
  • Hepatitis B reactivation in carriers
  • Hematologic reactions (pancytopenia, aplastic anemia)

Pediatric patients may be at increased risk for lymphoma and other malignancies. The long-term effects of etanercept on the developing immune system are not fully known, necessitating careful monitoring in pediatric patients.

Drug Interactions

While etanercept has fewer drug interactions compared to many other medications, there are some important considerations:

  • Live vaccines: Should not be given concurrently with etanercept due to the risk of infection
  • Anakinra: Combination with etanercept is not recommended due to increased risk of serious infections
  • Abatacept: Concurrent use is not recommended due to increased risk of serious adverse events
  • Other biologic DMARDs: Combination therapy has not been studied and may increase the risk of infections
  • Cyclophosphamide: Etanercept is not recommended for use with cyclophosphamide therapy
  • Sulfasalazine: There have been reports of pancytopenia in patients receiving both drugs

Etanercept may decrease the metabolism of drugs that are CYP450 substrates, potentially increasing their plasma concentrations. Dose adjustments of these medications may be necessary when starting or stopping etanercept.

Pediatric Considerations

Etanercept is one of the few biologic agents with specific pediatric indications, making it particularly relevant for pediatricians. Key considerations include:

  • Growth and Development: Regular monitoring of growth and development is crucial in pediatric patients receiving etanercept
  • Immunizations: Live vaccines should be avoided in patients receiving etanercept. It's important to update vaccinations before initiating therapy
  • Malignancy Risk: Pediatric patients may be at increased risk for lymphoma and other malignancies. Long-term surveillance is necessary
  • Infections: Children may be at higher risk for certain infections. Careful monitoring and prompt treatment of infections is essential
  • Weight-based Dosing: Accurate weight measurements are crucial for proper dosing in pediatric patients
  • Administration: Training caregivers or older children in proper injection technique is important for home administration
  • Psychosocial Impact: The impact of chronic medication use and regular injections on the child's quality of life should be considered
  • Transitional Care: Planning for transition to adult care is important for adolescents on long-term etanercept therapy

Pediatricians should work closely with pediatric rheumatologists or dermatologists when managing children on etanercept to ensure optimal care and monitoring.



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