What are the latest drug therapies for moderate to severe psoriasis?

Latest Drug Therapies for Moderate to Severe Psoriasis

The most effective treatments for moderate-to-severe psoriasis are IL-17 and IL-23 inhibitors, with bimekizumab, ixekizumab, and risankizumab demonstrating the highest efficacy rates for achieving PASI 90 responses. 1, 2

Biologic Therapies by Mechanism of Action

IL-23 Inhibitors

IL-23 inhibitors represent some of the newest and most effective treatments for moderate-to-severe psoriasis:

• Guselkumab:

  • FDA-approved for moderate-to-severe plaque psoriasis
  • Dosing: 100 mg at week 0, week 4, and every 8 weeks thereafter
  • Efficacy: 70% of patients achieve PASI 90 at week 16 (compared to 46.8% with adalimumab)
  • Particularly effective for patients who failed TNF inhibitors (66.1% achieved PASI 90 after switching) 1

• Risankizumab:

  • FDA-approved for moderate-to-severe plaque psoriasis
  • Superior efficacy compared to ustekinumab (77% vs 40% achieving PASI 90 at week 12)
  • Higher rates of complete clearance (PASI 100) compared to ustekinumab (45% vs 18%) 1

• Tildrakizumab:

  • FDA-approved for moderate-to-severe plaque psoriasis
  • Dosing: 100 mg at week 0, week 4, and every 12 weeks thereafter
  • Efficacy: 61% achieve PASI 75 at week 12 (compared to 48% with etanercept)
  • Favorable safety profile with lower risk of adverse events 1, 3

IL-17 Inhibitors

IL-17 inhibitors demonstrate rapid and high-level efficacy:

• Ixekizumab:

  • Dosing: 160 mg at week 0, then 80 mg every 2 weeks until week 12, followed by 80 mg every 4 weeks
  • Among the most effective biologics for achieving PASI 90 responses
  • Higher rate of adverse events compared to some other biologics 1, 3

• Secukinumab:

  • Effective for plaque psoriasis affecting various body sites including scalp and nails
  • Rapid onset of action 1

• Bimekizumab:

  • Newest IL-17 inhibitor that targets both IL-17A and IL-17F
  • Highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%) at 10-16 weeks
  • Demonstrated statistical superiority over all other biologics in achieving PASI 90 and PASI 100 2

TNF Inhibitors

While not the newest class, TNF inhibitors remain important options:

• Adalimumab:

  • Dosing: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose
  • Effective for psoriatic arthritis and various types of psoriasis (plaque, nail, palmoplantar)
  • Lower PASI 90 response rates compared to newer IL-17 and IL-23 inhibitors 1, 4

• Infliximab:

  • Weight-based dosing makes it suitable for patients of varying weights
  • High efficacy but increased risk of immunogenicity with intermittent use 5

IL-12/23 Inhibitor

• Ustekinumab:
  • Targets both IL-12 and IL-23 pathways
  • Weight-based dosing: 45 mg for patients <100 kg, 90 mg for patients ≥100 kg
  • Administered at weeks 0,4, and then every 12 weeks
  • Effective for various types of psoriasis including palmoplantar, nail, and scalp involvement
  • Lower efficacy compared to newer IL-17 and IL-23 inhibitors 1

Small Molecule Inhibitors

• Apremilast:

  • Oral phosphodiesterase-4 inhibitor
  • Dosing: Titration schedule to 30 mg twice daily
  • Moderate efficacy compared to biologics
  • Common side effects include diarrhea, nausea, and potential weight loss
  • May have beneficial metabolic effects in some patients 6, 7

• Tofacitinib:

  • JAK inhibitor, not FDA-approved for psoriasis but used off-label
  • Recommended dose: 5-10 mg twice daily
  • Consider zoster vaccination before initiation due to increased herpes zoster risk 1

Treatment Selection Algorithm

1. First-line for moderate-to-severe psoriasis:

   • IL-17 inhibitors (bimekizumab, ixekizumab) or IL-23 inhibitors (risankizumab, guselkumab) based on highest efficacy data 2, 5

2. For patients with concomitant psoriatic arthritis:

   • TNF inhibitors (adalimumab, infliximab) or IL-17 inhibitors (ixekizumab, secukinumab)

3. For patients with inflammatory bowel disease:

   • Avoid IL-17 inhibitors (may exacerbate IBD)
   • Consider TNF inhibitors or IL-23 inhibitors 7

4. For patients with metabolic syndrome:

   • Consider apremilast (potential weight loss benefit) or TNF inhibitors 7

5. For patients with history of malignancy:

   • Use caution with TNF inhibitors
   • Consider IL-23 inhibitors (though long-term safety data still accumulating) 1

Monitoring and Response Assessment

• Definitive response to IL-23 inhibitors should be assessed after 12 weeks of continuous therapy 1
• Consider dose escalation or combination with topical agents for partial responders
• Monitor for specific adverse events based on medication class:
  • TNF inhibitors: infections, reactivation of tuberculosis, demyelinating disorders
  • IL-17 inhibitors: candida infections, IBD exacerbation
  • Apremilast: depression, weight loss, gastrointestinal symptoms 6

Clinical Pearls and Pitfalls

• Pitfall: Assuming all biologics have similar efficacy. The newest IL-17 and IL-23 inhibitors consistently demonstrate superior efficacy over TNF inhibitors and ustekinumab 8, 5

• Pitfall: Failing to consider comorbidities when selecting therapy. Treatment choice should account for psoriatic arthritis, IBD, metabolic syndrome, and other comorbid conditions 7

• Pearl: For patients with inadequate response to one biologic class, switching to a different mechanism of action often yields better results (e.g., TNF failures responding well to IL-23 inhibitors) 1

• Pearl: Combination therapy with topicals, phototherapy, or traditional systemic agents may enhance efficacy for partial responders to biologics 1