What are the indications for Enbrel (etanercept)?

Indications for Enbrel (etanercept)

Enbrel (etanercept) is indicated for the treatment of moderate to severe psoriasis, moderate to severe psoriatic arthritis, adult and juvenile rheumatoid arthritis (as young as 2 years of age), and ankylosing spondylitis. 1, 2

FDA-Approved Indications

Adult Indications:

• Rheumatoid Arthritis (RA) 1

  • For moderate to severe active disease
  • Can be used with or without methotrexate 1

• Psoriatic Arthritis (PsA) 1

  • For moderate to severe disease
  • Inhibits radiographically detected damage of joints in patients with PsA 2

• Ankylosing Spondylitis (AS) 1

  • For active disease 3

• Plaque Psoriasis (PsO) 1

  • For moderate to severe disease 2

Pediatric Indications:

• Polyarticular Juvenile Idiopathic Arthritis (pJIA) 1

  • For patients 2 years of age or older 1

• Juvenile Psoriatic Arthritis (JPsA) 1

  • For patients 2 years of age or older 1

• Plaque Psoriasis 1

  • For patients 4 years of age or older 2, 1

Dosing Recommendations

Adult Dosing:

• Rheumatoid Arthritis and Psoriatic Arthritis: 50 mg once weekly with or without methotrexate 1
• Ankylosing Spondylitis: 50 mg once weekly 1
• Plaque Psoriasis: 50 mg twice weekly for 3 months, followed by 50 mg once weekly 1
  • Alternative regimen: 50 mg twice weekly for 3 months followed by 50 mg once weekly 2

Pediatric Dosing:

• All pediatric indications: 0.8 mg/kg weekly, with a maximum of 50 mg per week 1

Clinical Efficacy

Plaque Psoriasis:

• Short-term results: 49% of patients given 50 mg twice weekly achieved a PASI-75 at 12 weeks 2
• Step-down results: 54% of patients whose dose was decreased from 50 mg twice weekly to 25 mg twice weekly achieved a PASI-75 at 24 weeks 2
• Effective for difficult-to-treat areas:
  • Scalp psoriasis: 86.8% improvement in PSSI score at 12 weeks 2
  • Nail psoriasis: 41.7% improvement in NAPSI score at 12 weeks 2

Rheumatoid Arthritis:

• Provides rapid and sustained improvements in disease activity 4
• Inhibits radiographic progression in early disease 4
• Efficacy maintained for up to 9 years of treatment 5

Psoriatic Arthritis:

• ACR20 response rates of 50% vs 13% for placebo at 24 weeks 4
• Psoriatic arthritis response rates of 70% vs 23% for placebo 4
• Median improvement in skin lesions of 33% vs 0% for placebo 4

Ankylosing Spondylitis:

• Response rate of 57% compared with 22% for placebo after 24 weeks 6
• Significantly improved health-related quality of life 6

Important Safety Considerations

Boxed Warnings:

• Serious Infections: Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, invasive fungal infections, and other opportunistic pathogens 1
• Malignancies: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients 1

Baseline Monitoring Requirements:

• PPD (purified protein derivative) test for tuberculosis is required 2
• Liver function tests (LFT) and complete blood count (CBC) 2
• Hepatitis profile 2

Ongoing Monitoring:

• Periodic history and physical examination while on treatment 2
• Consider yearly PPD and periodic CBC and LFT 2
• Monitor for signs of infection 2
• For patients with history of viral hepatitis, monitor for reactivation 2

Contraindications:

• Sepsis 2
• Active serious infections 1

Common Adverse Effects:

• Mildly pruritic injection site reactions 2
• Upper respiratory tract infections 6

Serious Adverse Effects (rare):

• Serious infections (tuberculosis, opportunistic infections) 2
• Malignancies 2
• Drug-induced lupus without renal or CNS complications 2
• Cytopenia 2
• Multiple sclerosis 2
• Exacerbation and new onset of congestive heart failure 2
• Reactivation of hepatitis B virus 2

Combination Therapy Options

Etanercept may be combined with:

• Topical agents (steroids, vitamin D analogues) to enhance efficacy 2
• Acitretin to increase efficacy and potentially reduce etanercept dosing 2
• Methotrexate, particularly well-established for rheumatoid arthritis and psoriatic arthritis 2
• Phototherapy (NB-UVB), although long-term safety is not well studied 2

Important Clinical Pearls

• Do not start Enbrel during an active infection 1
• Avoid live vaccines while on etanercept 2
• Pregnancy category B 2
• Consider empiric anti-fungal therapy for patients at risk for invasive fungal infections who develop severe systemic illness 1
• Monitor patients previously infected with hepatitis B virus for reactivation 1
• Stop Enbrel if lupus-like syndrome or autoimmune hepatitis develops 1