Introduction
Enbrel (etanercept) is a biologic disease-modifying antirheumatic drug (DMARD) manufactured by Amgen. It is a tumor necrosis factor (TNF) inhibitor approved by the FDA in 1998 for the treatment of various autoimmune and inflammatory conditions. As a fusion protein, Enbrel represents a significant advancement in targeted immunomodulatory therapy, offering improved quality of life for patients with previously difficult-to-treat conditions.
Mechanism of Action
Enbrel works by competitively inhibiting tumor necrosis factor-alpha (TNF-α), a proinflammatory cytokine that plays a central role in inflammatory processes. The drug is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) TNF receptor linked to the Fc portion of human IgG1. This structure allows Enbrel to bind specifically to both TNF-α and lymphotoxin-alpha (TNF-β), preventing these cytokines from interacting with their natural cell surface receptors. By neutralizing TNF activity, Enbrel reduces the inflammatory cascade, decreases cellular infiltration into inflamed tissues, and modulates the expression of adhesion molecules responsible for leukocyte migration.
Indications
FDA-approved indications include:
- Moderate to severe rheumatoid arthritis (RA) in adults
- Polyarticular juvenile idiopathic arthritis (JIA) in children ages 2 years and older
- Psoriatic arthritis
- Ankylosing spondylitis
- Moderate to severe plaque psoriasis in adults and children ages 4 years and older
Dosage and Administration
Standard dosing:- Rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis: 50 mg weekly administered subcutaneously
- Plaque psoriasis: 50 mg twice weekly for 3 months, then reduced to 50 mg weekly
- Juvenile idiopathic arthritis: Weight-based dosing (0.8 mg/kg weekly, maximum 50 mg per week)
- Administered as subcutaneous injection
- Available in prefilled syringes (25 mg/0.5 mL, 50 mg/mL) and SureClick autoinjectors
- Rotate injection sites between thighs, abdomen, and upper arms
- Allow refrigerated medication to reach room temperature (15-30 minutes) before injection
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution; no specific dosage recommendations
- Elderly: No dosage adjustment required
- Pregnancy: Category B - use only if clearly needed
Pharmacokinetics
Absorption: Bioavailability approximately 76% following subcutaneous administration. Peak serum concentrations reached in approximately 48 hours. Distribution: Volume of distribution is 12 liters. The fusion protein component binds specifically to TNF. Metabolism: Believed to be degraded by peptide hydrolysis throughout the body. No cytochrome P450 enzyme involvement. Elimination: Half-life approximately 70 hours (range 46-139 hours). Clearance increased in the presence of anti-etanercept antibodies. Eliminated primarily through proteolytic pathways.Contraindications
- Sepsis or active infections
- Hypersensitivity to etanercept or any component of the formulation
- Concurrent live vaccines in pediatric patients
- Patients with known hepatitis B virus reactivation risk
Warnings and Precautions
Serious infections: Increased risk of bacterial, fungal, viral, and opportunistic infections, including tuberculosis. Evaluate patients for latent TB before initiation and monitor during therapy. Malignancy: Increased risk of lymphoma and other malignancies, particularly in children and adolescents. Hepatitis B reactivation: Screen for HBV infection before initiation. Monitor carriers during and for several months after therapy. Neurologic events: Rare cases of new onset or exacerbation of demyelinating disorders. Hematologic events: Pancytopenia, including aplastic anemia, has been reported. Heart failure: Worsening or new onset congestive heart failure may occur. Hypersensitivity reactions: Anaphylaxis and angioedema may occur.Drug Interactions
- Live vaccines: Avoid concurrent administration
- Anakinra: Increased risk of serious infections (not recommended)
- Abatacept: Increased risk of serious infections (not recommended)
- Other TNF blockers: Increased risk of adverse effects (contraindicated)
- Cyclophosphamide: Avoid combination due to increased infection risk
- Sulfasalazine: Possible decreased etanercept clearance
Adverse Effects
Most common (>10%): Injection site reactions (erythema, itching, pain, swelling), upper respiratory infections, headache Common (1-10%): Rash, abdominal pain, vomiting, pharyngitis, cough, fever, dizziness, sinusitis, nausea Serious (<1%):- Serious infections (sepsis, pneumonia, TB)
- Malignancies (lymphoma, skin cancer)
- Congestive heart failure
- Blood dyscrasias
- Neurologic events (demyelinating disorders)
- Lupus-like syndrome
- Severe allergic reactions
Monitoring Parameters
Baseline:- Complete blood count with differential
- Liver function tests
- Renal function tests
- Hepatitis B and C serology
- Tuberculosis screening (PPD or interferon-gamma release assay)
- Pregnancy test if appropriate
- Signs and symptoms of infection at each visit
- Injection sites for reactions
- Clinical response and disease activity measures
- CBC and LFTs every 3-6 months
- Annual skin examination for malignancy screening
- Regular assessment for neurologic symptoms
Patient Education
- Instruct on proper injection technique and site rotation
- Recognize and report signs of infection (fever, cough, flu-like symptoms)
- Avoid live vaccines during therapy
- Seek immediate medical attention for allergic reactions
- Inform all healthcare providers about Enbrel therapy
- Report unusual fatigue, bruising, or bleeding
- Women of childbearing potential should discuss contraception
- Store medication properly (refrigerated at 2-8°C)
- Do not shake the solution
- Dispose of needles and syringes properly
References
1. FDA Prescribing Information: Enbrel (etanercept) 2. Singh JA, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2016;68(1):1-26 3. Menter A, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. J Am Acad Dermatol. 2019;80(4):1029-1072 4. Lovell DJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. N Engl J Med. 2000;342(11):763-769 5. Weinblatt ME, et al. A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999;340(4):253-259 6. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Updated periodically 7. Micromedex Solutions [Internet]. Truven Health Analytics. Updated periodically
Note: This monograph provides general information and should not replace professional medical advice. Always consult with a healthcare provider for specific medical guidance.