What is the best treatment for severe plaque psoriasis?

Best Treatment for Severe Plaque Psoriasis

Biologic therapy with IL-12/23 inhibitor ustekinumab is recommended as the first-line treatment for severe plaque psoriasis due to its superior efficacy, favorable safety profile, and excellent drug survival rates. 1, 2

Treatment Algorithm for Severe Plaque Psoriasis

First-Line Therapy: Biologics

1. IL-12/23 Inhibitor (Preferred First-Line)

   • Ustekinumab (Stelara) - Highest efficacy and drug survival rates 1, 3
     • Dosing:
       • For patients ≤100 kg: 45 mg subcutaneously at weeks 0,4, then every 12 weeks 1
       • For patients >100 kg: 90 mg subcutaneously at weeks 0,4, then every 12 weeks 1
     • Consider increasing to every 8 weeks for inadequate responders 1

2. TNF Inhibitors (Alternative First-Line)

   • Adalimumab (Humira) - 80 mg at week 0, then 40 mg every other week 1, 4
   • Etanercept (Enbrel) - 50 mg twice weekly for 12 weeks, then 50 mg weekly 1, 5
   • Infliximab (Remicade) - 5 mg/kg at weeks 0,2,6, then every 8 weeks 1

Evaluation of Treatment Response

• Assess response at appropriate timepoints as per guidelines:

  • Ustekinumab: Evaluate at week 28 1, 2
  • Adalimumab: Evaluate at week 16 1
  • Etanercept: Evaluate at week 12 1
  • Infliximab: Evaluate at week 10 1

• Primary success defined as achieving PASI 75 (75% improvement in Psoriasis Area and Severity Index) 2

Combination Therapy Options

For patients with inadequate response to biologic monotherapy, consider combination with:

1. Topical therapies

   • High-potency corticosteroids with or without vitamin D analogues 1

2. Systemic agents

   • Methotrexate - can be combined with biologics to augment efficacy 1
   • Acitretin - may be combined with biologics 1

3. Phototherapy

   • Narrowband UVB can be combined with biologics to enhance efficacy 1

Comparative Efficacy of Biologics

• Ustekinumab: Highest probability of achieving PASI 75 at week 24 (75.5%) and PASI 50 at time of primary failure assessment (80.7%) 2
• Infliximab: Greatest probability of response at primary endpoint (week 10) 2
• Adalimumab: Moderate efficacy with good safety profile 2
• Etanercept: Lower efficacy compared to other biologics but established safety record 2

Special Considerations

• Psoriatic arthritis: If present, TNF inhibitors or ustekinumab are recommended 1
• Difficult-to-treat areas:
  • Scalp: Ustekinumab and etanercept are effective 1
  • Nails: Ustekinumab and etanercept show good efficacy 1
  • Palmoplantar: Ustekinumab shows good efficacy 1

Safety Considerations

• Infection risk: Screen for tuberculosis and other infections before initiating therapy 1
• Monitoring: Regular follow-up to assess for adverse events 1
• Vaccination: Ensure patients are up-to-date on vaccinations before starting therapy 1

Common Pitfalls and Caveats

• Drug survival: Despite high efficacy in clinical trials, secukinumab has shown lower drug survival rates in real-world settings compared to ustekinumab 3
• Dosage adjustments: Higher than approved dosages are frequently needed for optimal response with most biologics except adalimumab 3
• Treatment interruption: If therapy is interrupted, most patients can regain clinical efficacy upon reinitiating treatment 6
• Biosimilars: No significant differences in efficacy or safety between originator and biosimilar versions of infliximab or etanercept 3

Pediatric Considerations

• For pediatric patients with severe plaque psoriasis:
  • Etanercept is FDA-approved for ages 4 years and older 1
  • Ustekinumab is FDA-approved for ages 12 years and older 1