What is the recommended treatment for moderate to severe plaque psoriasis?

Treatment Recommendations for Moderate to Severe Plaque Psoriasis

Biologic therapies are the recommended first-line treatment for moderate to severe plaque psoriasis, with IL-17 and IL-23 inhibitors showing the highest efficacy rates. 1

First-Line Treatment Options

TNF-α Inhibitors

• Etanercept:

  • Dosing: 50 mg subcutaneously twice weekly for 12 weeks, then 50 mg once weekly for maintenance 1
  • Strong recommendation (Grade A) for moderate-to-severe plaque psoriasis
  • Effective for scalp and nail involvement

• Infliximab:

  • Dosing: 5 mg/kg intravenous infusion at weeks 0,2,6, then every 8 weeks 1
  • Strong recommendation (Grade A) for moderate-to-severe plaque psoriasis
  • May require dose increases up to 10 mg/kg or more frequent dosing (every 4 weeks) in some patients

IL-12/IL-23 Inhibitor

• Ustekinumab:
  • Dosing: Weight-based dosing of 45 mg (≤100 kg) or 90 mg (>100 kg) at weeks 0,4, then every 12 weeks 1
  • Strong recommendation (Grade A) for moderate-to-severe plaque psoriasis
  • Particularly effective when psoriasis is associated with psoriatic arthritis

IL-17 Inhibitors

• Secukinumab:
  • Dosing: 300 mg subcutaneously at weeks 0,1,2,3,4, then every 4 weeks 2
  • FDA-approved for moderate-to-severe plaque psoriasis
  • Rapid onset of action

IL-23 Inhibitors

• Guselkumab:

  • Dosing: 100 mg subcutaneously at weeks 0,4, then every 8 weeks 1
  • Strong recommendation (Grade A) for moderate-to-severe plaque psoriasis
  • Effective for scalp, nail, and palmoplantar involvement

• Tildrakizumab:

  • Dosing: 100 mg subcutaneously at weeks 0,4, then every 12 weeks 1
  • Strong recommendation (Grade A) for moderate-to-severe plaque psoriasis

Comparative Efficacy

Recent network meta-analysis data indicates that IL-17 and IL-23 inhibitors demonstrate the highest efficacy rates for moderate-to-severe plaque psoriasis 3:

• Bimekizumab (IL-17A/F inhibitor) showed the highest probability of achieving:

  • PASI 75: 92.3%
  • PASI 90: 84.0%
  • PASI 100: 57.8%

• Bimekizumab demonstrated statistical superiority over all other biologics in achieving PASI 90 and PASI 100 thresholds 3

• In head-to-head trials, bimekizumab was superior to adalimumab with 86.2% vs 47.2% PASI 90 response at week 16 4

Combination Therapies

For patients with inadequate response to biologic monotherapy, consider these evidence-based combinations:

1. Biologic + Topical therapy:

   • Combination of biologics with high-potency corticosteroids with/without vitamin D analogs 1
   • Strong recommendation (Grade A) for etanercept with topicals

2. Biologic + Methotrexate:

   • Ustekinumab + methotrexate (Grade B recommendation) 1
   • Infliximab + methotrexate (Grade B recommendation) 1
   • Etanercept + methotrexate (Grade B recommendation) 1

3. Biologic + Phototherapy:

   • Ustekinumab + narrowband UVB (Grade B recommendation) 1
   • Etanercept + narrowband UVB (Grade B recommendation) 1

Special Considerations

Psoriatic Arthritis

• When psoriasis is accompanied by psoriatic arthritis, prioritize:
  • TNF-α inhibitors (infliximab, etanercept) 1
  • Ustekinumab 5
  • Secukinumab 2

Difficult-to-Treat Areas

• Scalp psoriasis: Etanercept, infliximab, ustekinumab, guselkumab (all Grade A-C recommendations) 1
• Nail psoriasis: Etanercept, infliximab, ustekinumab (all Grade A-B recommendations) 1
• Palmoplantar psoriasis: Infliximab, ustekinumab, guselkumab (all Grade B recommendations) 1

Treatment Failure Management

• Primary failure (initial non-response):

  • Switch to a biologic with a different mechanism of action
  • Failure of TNF-α inhibitor does not preclude response to another TNF-α inhibitor, but may suggest reduced efficacy with others in this class 1

• Secondary failure (loss of efficacy over time):

  • Consider presence of anti-drug antibodies
  • Consider adding methotrexate to increase biologic drug survival
  • Switch to a biologic with a different mechanism of action 1

Monitoring Recommendations

• Evaluate response after 12-16 weeks of continuous therapy
• Prior to initiating treatment:
  • Screen for tuberculosis
  • Test for hepatitis B
  • Complete age-appropriate vaccinations
  • Consider baseline CBC and liver function tests

Common Pitfalls to Avoid

1. Inadequate dosing: Ensure weight-based dosing for agents like ustekinumab (45 mg for ≤100 kg, 90 mg for >100 kg)
2. Premature discontinuation: Allow adequate time (12-16 weeks) before determining treatment failure
3. Ignoring comorbidities: Consider presence of psoriatic arthritis when selecting therapy
4. Neglecting difficult-to-treat areas: Special attention to scalp, nail, and palmoplantar involvement may require specific biologic choices
5. Overlooking combination therapy: Consider adding methotrexate, phototherapy, or topicals for enhanced efficacy in partial responders