Generic Name

Enbrel

Mechanism

• Decoy receptor: Enbrel couples the extracellular ligand‑binding domain of the human TNF receptor type 2 (p75) with the Fc portion of human IgG1.
• TNF‑α neutralization: It binds soluble and membrane‑bound TNF‑α, preventing interaction with cell surface receptors (p55 and p75).
• Down‑stream effects:
• Inhibition of NF‑κB activation → reduced pro‑inflammatory cytokine production.
• Diminished leukocyte adhesion & migration.
• Restoration of immune homeostasis in target tissues.

Pharmacokinetics

Indications

• Rheumatoid arthritis (active disease; with or without methotrexate).
• Psoriatic arthritis (active disease).
• Plaque psoriasis (severe or moderate, inadequate response to topical agents).
• Ankylosing spondylitis (active disease).
• Juvenile idiopathic arthritis (polyarticular, active).

> Note: For ankylosing spondylitis, enbrel is licensed in the US but not globally supervised; alternative TNF‑α inhibitors may be preferred.

Contraindications

• Active severe infections (including tuberculosis) – screen with tuberculin skin test or interferon‑γ release assay.
• Uncontrolled heart failure (NYHA III/IV).
• Severe uncontrolled asthma or COPD exacerbations at presentation.
• Known hypersensitivity to etanercept or any excipient.
• Active malignancy (certain solid tumors, hematologic cancers) – decision deferred to specialist.
• Pregnancy: Category B; use only if benefits outweigh risks. Avoid during lactation.

> Warnings:
• Infections: ↑ risk of bacterial, viral (HBV, HCV), and opportunistic infections.
• Malignancy: Slightly increased risk of non‑melanoma skin cancers, lymphoma (case‑by‑case).
• Autoimmune phenomena: Rare cases of drug‑induced lupus, vasculitis.

Dosing

• Route: Subcutaneous using pre‑filled syringe or pre‑filled pen.
• Administration schedule: Maintain consistent interval for steady plasma concentrations.
• Switching: Transition from other TNF‑α inhibitors possible; monitor for infusion reactions or anti‑drug antibodies.

Adverse Effects

Common (≥10 %)
• Injection‑site reactions (pain, erythema, pruritus)
• Upper respiratory tract infections
• Headache

Serious (≥1 %)
• Serious infections (sepsis, tuberculosis)
• Opportunistic infections (cryptococcal, histoplasmosis)
• Malignancies (non‑melanoma skin cancer, lymphomas)
• Autoimmune cytopenias (anemia, thrombocytopenia)
• Allergic reactions (anaphylaxis, drug‑related lupus)
• Hepatotoxicity (elevated transaminases)

> Monitoring: Annual screening for latent TB, regular liver function tests, vigilance for rash, lymphadenopathy or unexplained fevers.

Monitoring

• Baseline:
• CBC, LFTs, serum creatinine.
• TB screening, hepatitis B/C serology.
• During therapy:
• CBC, LFTs every 3 months (or more frequently if abnormal).
• Signs of infection → prompt evaluation.
• Immunogenicity: Rare anti‑drug antibody formation – clinically significant only if loss of efficacy.
• Pregnancy & Lactation: Monitor fetal ultrasound if pregnant; advise breast‑feeding discontinuation.

Clinical Pearls

• Pegylatable? – Enbrel is not pegylated; it has a relatively short half‑life compared to other biologics (adalimumab, infliximab).
• Dose adjustment: Body‑weight dosing (5× ULN.
• Drug holidays: Interim drug interrupt can reduce anti‑drug antibody titers but may increase disease flare; use sparingly.
• Immunization: Live vaccines contraindicated during therapy; inactivated vaccines safe on the day of or the day before injection.
• Translocation to joint fluid: Enbrel is detected in synovial fluid at concentrations above the minimal effective TNF‑α concentration – supports efficacy in RA joints.

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• *Source: FDA Prescribing Information, EMA Summary of Product Characteristics, UpToDate, peer‑reviewed pharmacology textbooks.*