Etanercept

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Etanercept
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Indications of etanercept in dermatology

  • FDA approaved
    • Plaque psoriasis.
    • Psoriatic arthritis.
  • Off-label use
    • Pemphigus vulgaris.
    • Pityriasis rubra pilaris.
    • SAPHO syndrome
    • Necrobiosis lipoidica.
    • Acrodermatitis continua of Hallopeau.
    • Graft-versus-host disease.
    • Pyoderma gangrenosum, refractory.
    • Aphthous stomatitis.
    • Behçet’s disease:25 mg twice weekly.
    • Hidradenitis suppurativa.
    • Eosinophilic fasciitis.
    • Dermatomyositis.
    • Palmoplantar pustulosis.
    • Erythema nodosum.
    • Cutaneous granulomas.
    • Atopic dermatitis.
    • Toxic epidermal necrolysis.

Dosage

  • Psoriatic arthritis: Once-weekly dosing: 50 mg once weekly
  • Acute graft-versus-host disease: 0.4 mg/kg (maximum: 25 mg/dose) twice weekly for 8 weeks (in combination with methylprednisolone).
  • Chronic graft-versus-host disease (refractory), treatment: SubQ: 25 mg twice weekly for 4 weeks, followed by 25 mg once weekly for 4 weeks (in combination with corticosteroids and/or immunosuppressive therapy).
  • Plaque psoriasis:
    • 50 mg twice weekly SC for 3 months (starting doses of 25 or 50 mg once weekly have also been used ).
    • Maintenance dose: 50 mg once weekly.
  • Plaque psoriasis: Children and Adolescents 4 to 17 years Enbrel: SubQ: 0.8 mg/kg/dose once weekly; maximum dose: 50 mg/dose.
  • Pyoderma gangrenosum, refractory :): SubQ: 25 to 50 mg SC twice weekly.
  • Pemphigus vulgaris: 25–50 mg twice weekly for 4 months.
  • Pityriasis rubra pilaris: 50 mg weekly for 5 months.
  • Behçet’s disease: 25 mg twice weekly.

Mechanism of action

  • Etanercept is anti-tumor necrosis factor (anti-TNF) agent that binds and inhibits the activity of TNF.
  • It inhibits soluble and membrane-bound TNF-α.

Baseline Monitoring

  • Ask about:
    • Personal and family history closely for multiple sclerosis and related demyelinating disorders.
  • Labs
    • PPD.
    • Chest x ray in selective cases.
    • CBC.
    • LFT.

Follow Up Monitoring

  • Periodic skin examinations in all patients during therapy, particularly those at increased risk of skin cancer.
  • PPD: 6- to 12-month intervals (QuantiFERON-TB Gold testing (interferon-gamma release assay) may be a more appropriate primary test in patients with risk factors for false-negative tuberculin skin test results.
  • LFT

Side effects of etanercept

  • COMMON
    • Injection site reactions: Use Cool compresses and 1% hydrocortisone ointment.
    • Upper respiratory infection.
  • RARE
    • Reactivation tuberculosis.
    • Malignancy.
    • Alopecia.
    • Spessis.
    • Anaphylaxis/hypersensitivity reactions.
    • Lupus-like syndrome or autoimmune hepatitis.
    • Demyelinating CNS disease.
    • Heart failure.
    • Pancytopenia (rare).
    • Reactivation of hepatitis B (rare).
    • Myelitis, optic neuritis, pharyngitis, headache, rhinitis, abdominal pain, nausea, vomiting, rash.

Contraindications

  • Hypersensitivity to etanercept or any component of the formulation
  • Patients at risk of sepsis syndrome (eg, immunocompromised, HIV positive).
  • Concurrent administration with  anakinra.
  • Family history of  demyelinating diseases. 

Interactions of etanercept

  • Risk of infections: immunosuppressants.
  • Avoid combination with
    • Abatacept
    • Anakinra
    • DMARDs
    • Cyclophosphamide
    • Tacrolimus (Topical)
    • Intravesical BCG
    • Belimumab
    • Canakinumab
    • Certolizumab Pegol
    • Cladribine
    • Tocilizumab
  • Etanercept + methotrexate is approved for the treatment of rheumatoid arthritis and psoriatic arthritis.

Pregnancy & Lactation

  • Pregnancy Category B
  • Consider discontinuing etanercept 15 days prior to attempting pregnancy
  • The American Academy of Dermatology considers TNFα blocking agents for the treatment of psoriasis to be compatible with pregnancy and breastfeeding.
  • Etanercept and other TNF inhibitors be avoided after the first trimester.
  • Tumor necrosis factor alpha (TNFα) blocking agents are considered to have low to moderate risk when used in pregnancy.
  • Neonate/infant should be considered immunosuppressed for 1 to 3 months following in utero exposure.
  • Etanercept is minimally excreted in breast milk.
  • For more information

Precautions

  • Discontinue etanercept if a patient develops a serious infection or sepsis.
  • Consider empiric antifungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Do not initiate etanercept therapy in patients with an active infection, including clinically important localized infection
  • Patients with initial negative tuberculin skin tests should receive continued monitoring for tuberculosis during and after treatment.
  • Use with caution in patients with moderate to severe alcoholic hepatitis.
  • Use with caution in patients with a history of seizures.
  • Malignancies have been reported among children and adolescents.
  • Use with caution in elderly patients.
  • Patients should be brought up to date with all immunizations before initiating therapy.
  • Monitor signs/symptoms of malignancy (eg, splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss).

Drug Info

  • Etanercept is a fusion protein containing the TNF‐α receptor (TNFαRII) fused with a humanized immunoglobulin fragment.
  • Etanercept has been used together with narrowband UVB without an increase in adverse events.
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