Etanercept

Approved Indications:

• Rheumatoid Arthritis (RA):
  Moderate to severe active rheumatoid arthritis in adults to reduce signs and symptoms, inhibit structural damage, and improve physical function.
• Juvenile Idiopathic Arthritis (JIA):
  Active polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.
• Psoriatic Arthritis (PsA):
  Active and progressive psoriatic arthritis in adults.
• Ankylosing Spondylitis (AS):
  Active ankylosing spondylitis in adults.
• Plaque Psoriasis:
  Moderate to severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
• Chronic Moderate to Severe Hidradenitis Suppurativa:
  In adults and adolescents (12 years and older) with inadequate response to conventional systemic therapy.
• Other Indications:
• Adult patients with active non-radiographic axial spondyloarthritis with objective signs of inflammation.
• Pediatric patients with enthesitis-related arthritis and juvenile psoriatic arthritis (JPsA).

Clinically Accepted Off-Label Uses:

• Behçet’s disease
• Other inflammatory autoimmune conditions as determined by specialists.

Route: Subcutaneous injection

Adults:

• Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis:
  50 mg once weekly or 25 mg twice weekly.
• Plaque Psoriasis:
  50 mg twice weekly for 3 months, followed by 50 mg once weekly.
• Hidradenitis Suppurativa:
  50 mg once weekly.

Juvenile Idiopathic Arthritis (≥2 years):

• 0.8 mg/kg once weekly (maximum 50 mg per dose).

Elderly:

• Same dosing as adults; monitor for increased infection risk.

Renal or Hepatic Impairment:

• No dose adjustment needed; use caution.

Administration Instructions:

• Inject subcutaneously in the thigh, abdomen, or upper arm.
• Rotate injection sites.
• Administer with or without food.
• Prefilled syringes and auto-injectors are available for patient self-administration.

Etanercept is a recombinant fusion protein that acts as a soluble tumor necrosis factor (TNF) receptor. It binds both TNF-α and TNF-β (lymphotoxin-alpha), neutralizing their biological activity by preventing interaction with cell surface TNF receptors. TNF is a pro-inflammatory cytokine central to the pathogenesis of autoimmune inflammatory diseases. By inhibiting TNF activity, etanercept reduces inflammation, halts disease progression, and improves clinical symptoms in TNF-mediated disorders.

• Absorption:
  Following subcutaneous administration, peak serum concentrations occur within 48 to 60 hours.
• Bioavailability:
  Approximately 58%.
• Distribution:
  Volume of distribution approximately 7.6 L.
• Metabolism:
  Degraded by proteolytic enzymes into small peptides and amino acids; not metabolized via CYP enzymes.
• Half-life:
  Approximately 70–115 hours (about 3–5 days).
• Excretion:
  Metabolites eliminated via reticuloendothelial system; not renally excreted.

• Pregnancy:
  Classified as FDA Pregnancy Category B. Animal studies showed no teratogenicity; however, there are limited controlled human data. Use only if clearly needed after risk-benefit evaluation.
• Lactation:
  Limited data on excretion in human milk. Caution advised; breastfeeding is generally not recommended during treatment.

• Primary Class: Immunomodulator
• Subclass: Tumor Necrosis Factor (TNF) inhibitor; Biologic Disease-Modifying Antirheumatic Drug (bDMARD)

• Known hypersensitivity to etanercept or any component of the formulation
• Active infections including tuberculosis, sepsis, or opportunistic infections
• Moderate to severe heart failure (NYHA class III/IV)
• Concurrent use with other biologic immunosuppressants or live vaccines

• Infections:
  Increased risk of serious infections including tuberculosis, bacterial, viral, and fungal infections. Screen for latent TB before treatment.
• Malignancies:
  Reports of lymphoma and other malignancies, including hepatosplenic T-cell lymphoma in pediatric and young adult patients.
• Neurological Events:
  Rare cases of demyelinating disorders (e.g., multiple sclerosis).
• Hematologic Events:
  Rare reports of pancytopenia, aplastic anemia.
• Heart Failure:
  May worsen congestive heart failure; monitor closely.
• Immunization:
  Avoid live vaccines during and after treatment.
• Monitoring:
  Regular clinical and laboratory monitoring for infection signs, blood counts, and liver function.

Common (≥10%):

• Injection site reactions (erythema, itching, swelling)
• Upper respiratory infections
• Headache
• Rash

Less Common / Serious:

• Serious infections (sepsis, pneumonia, tuberculosis)
• Allergic reactions including anaphylaxis
• Autoimmune phenomena (lupus-like syndrome)
• Hematologic abnormalities
• Malignancies

• Immunosuppressants (e.g., abatacept, anakinra): Increased risk of serious infections; concurrent use not recommended.
• Live Vaccines: Contraindicated during therapy; may reduce vaccine efficacy.
• Methotrexate: Often used in combination; no significant pharmacokinetic interaction but additive immunosuppression occurs.

• Updated EULAR and ACR guidelines recommend etanercept as a first-line biologic agent after inadequate response to conventional DMARDs in RA and other inflammatory diseases.
• Recent FDA updates reinforce screening and monitoring for latent TB and serious infections.
• EMA and WHO emphasize individualized treatment plans considering infection risk and malignancy history.

• Store refrigerated at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Do not freeze.
• Keep in original packaging until use.
• If necessary, may be kept at room temperature (up to 25°C or 77°F) for up to 14 days; discard if not used within this period.
• Avoid shaking.