Etanercept is a biologic TNF inhibitor commonly used to control ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, and rheumatoid arthritis. Etanercept is a soluble receptor that binds both TNF-alpha and TNF-beta to inhibit the inflammatory response in joints and skin that is characteristic of these autoimmune disorders. The drug can be used as a monotherapy or taken with other immunosuppressants, such as methotrexate. 

FDA approved uses for etanercept[1][2][3][4][5][4][3][2][1]:

• Ankylosing spondylitis
• Juvenile idiopathic arthritis (2 years or older)
• Plaque psoriasis (4 years or older)
• Psoriatic arthritis
• Rheumatoid arthritis

Off-label uses (not FDA approved):

• Acute graft-versus-host disease (combined with methylprednisolone)
• Behcet disease
• Hidradenitis suppurativa 
• Kawasaki disease 
• Pemphigus vulgaris 
• Pustular psoriasis 
• Pyoderma gangrenosum 
• Scleroderma/systemic sclerosis 
• Still disease 

Etanercept is a biologic tumor necrosis factor (TNF) inhibitor; the drug acts as a soluble TNF receptor and binds TNF-alpha and TNF-beta.[6] TNF is a cytokine that can bind to TNF receptor 1 (TNFR1) or TNF receptor 2 (TNFR2) and is involved in inflammation and the immune response.[7] When TNF binds to TNFR1 or TNFR2, it activates important inflammatory pathways, such as NFkB and MAPK. The structure of Etanercept consists of two p75 TNF receptors fused to the Fc portion of human IgG.[6] Etanercept works by blocking the effects of TNF-alpha, a pro-inflammatory cytokine that becomes elevated in psoriasis, rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis, and ankylosing spondylitis.

Etanercept administration is via subcutaneous injection, usually on the thigh, lower abdomen, or upper arm. If given on the abdomen, the injection should not be within the 2-inch area around the navel. Injections should be administered at least 1 inch away from previous injection sites. The medication comes in a pre-filled syringe, automatic injection device, or multiple-dose vial. After the initial injection of Etanercept at the doctor’s office, the patient can self-inject at home.[8]

For the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, 50 mg of etanercept is injected once a week. For psoriasis, the dosage is 50 mg twice weekly for three months, followed by 50 mg once weekly. Children with juvenile idiopathic arthritis are administered 0.8 mg/kg once a week, up to 50 mg.

The most common adverse effects include[1]:

• Infection (viral, bacterial, and fungal – mostly upper respiratory tract infections)
• Injection site reaction (erythema, itching, pain, swelling, bleeding, bruising)

Rare adverse effects include (in alphabetical order):

• Blood and lymph disorders: aplastic anemia, leukopenia, myelodysplastic syndrome, neutropenia, pancytopenia, thrombocytopenia[9]
• Cancers: lymphoma [10], skin cancers
• Cardiopulmonary problems: congestive heart failure, interstitial lung disease[11]
• Gastrointestinal and liver problems: autoimmune hepatitis,[12] diarrhea,[13] elevated transaminases,[14] inflammatory bowel disease,[15] nausea[16] 
• Immune and inflammatory conditions:  angioedema,[17] hypersensitivity reaction,[18] lupus-like syndrome,[11] non-neutralizing anti-Etanercept antibodies,[1] pyrexia,[16] sarcoidosis, uveitis, vasculitis
• Infections: aspergillosis,[19] candidiasis,[19] coccidioidomycosis, cryptococcus,[19] herpes zoster, histoplasmosis,[19] legionella pneumonia,[20] listeriosis,[19] nocardiosis,[19] pneumocystis pneumonia, reactivation of Hepatitis B or TB,[21] salmonella infection,[19] septic arthritis 
• Nervous system disorders: headache.[5] multiple sclerosis, optic neuritis, paresthesias, seizures, transverse myelitis
• Skin disorders: cutaneous lupus erythematosus,[22] erythema multiforme,[22] new or worsening psoriasis, rash, Stevens-Johnson syndrome,[22] toxic epidermal necrolysis,[22] urticaria

US boxed warnings

Infections, including tuberculosis:

Patients using etanercept have an increased risk of acquiring serious and/or fatal infections, including the development of active tuberculosis or reactivation of latent tuberculosis. There are reports of various bacterial, viral, and fungal infections, including invasive fungal (aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, and pneumocystosis) and opportunistic infections (legionellosis, listeriosis). 

Infections were more common in patients that received adjunct immunosuppressive medications, such as methotrexate or corticosteroids. Medical providers should exercise caution when prescribing etanercept to patients at higher risk for infections, including elderly patients, immunocompromised patients, patients with a history of recurrent/chronic/opportunistic infections, and patients exposed to tuberculosis or endemic mycoses. Physicians should consider empiric antifungal therapy for patients living in or traveling to endemic areas with an increased risk of invasive fungal infections.

Malignancies:

Reports exist of malignancies in patients receiving etanercept, especially in children and adolescents. Lymphomas were most commonly reported, followed by melanoma and other skin cancers. Though the connection between etanercept and malignancies is not fully understood, clinical trials and case reports showed an increased rate of lymphoma and other malignancies in patients on etanercept compared to the general population. However, it is worth noting that rheumatoid arthritis alone has associations with increased rates of lymphoma and leukemia.

Etanercept contraindications include patients with sepsis. Patients should not start etanercept during active bacterial infections, including tuberculosis (active or latent), active herpes zoster infection, active or chronic untreated Hepatitis B or C infection, or active invasive fungal infections.[23] Patients should not use etanercept if they have a hypersensitivity reaction to the medication ingredients.