What are the recent advances in the treatment of psoriasis?

Recent Advances in the Treatment of Psoriasis

The most significant recent advances in psoriasis treatment include biologics targeting TNF-α, IL-17, and IL-23 pathways, JAK inhibitors, and combination therapies that have revolutionized management of moderate-to-severe disease, while topical vitamin D analogs combined with corticosteroids remain the cornerstone for mild disease. 1

Classification of Disease Severity

• Mild psoriasis: <10% body surface area (BSA)
• Moderate-to-severe psoriasis: ≥10% BSA or significant impact on quality of life 1

Advances in Topical Therapies

First-Line Topical Treatments

• Combination therapy: Potent corticosteroids with vitamin D analogs (calcipotriene/calcipotriol) is superior to either agent alone 1
  • Provides synergistic effects
  • Reduces corticosteroid-related side effects
  • Extends duration of treatment benefit and remission 2
  • Maximum 100g of vitamin D analogs weekly to avoid hypercalcemia 2

Newer Topical Agents

• Calcitriol: Less irritating vitamin D analog, better tolerated on face and intertriginous areas 2
• Topical calcineurin inhibitors (tacrolimus, pimecrolimus): Particularly effective for facial and intertriginous psoriasis with no risk of skin atrophy 1
• Tazarotene: Retinoid with efficacy comparable to mid-potency corticosteroids, best used in combination with corticosteroids to minimize irritation 2, 1
• Roflumilast: PDE4 inhibitor for plaque psoriasis 3
• Tapinarof: Aryl hydrocarbon receptor modulating agent 3

Special Considerations for Topical Therapy

• Inverse psoriasis: Lower potency corticosteroids or calcineurin inhibitors to minimize atrophy risk 2
• Scalp psoriasis: Medicated shampoos with coal tar, salicylic acid, or solutions/foams of corticosteroids or vitamin D analogs 1
• Genital psoriasis: Requires careful approach due to increased penetration and irritation risk 2

Advances in Systemic Therapies

Biologics

Biologics have revolutionized treatment of moderate-to-severe psoriasis with higher efficacy and improved safety profiles:

1. TNF-α inhibitors (e.g., adalimumab):

   • Effective for both skin and joint manifestations 4
   • Dosing: 80mg initial dose, followed by 40mg every other week 4
   • Particularly useful when psoriatic arthritis is present 2

2. IL-17 inhibitors:

   • Higher efficacy for skin involvement than TNF inhibitors 2
   • Strong recommendation for both skin and nail psoriasis 2

3. IL-23 inhibitors:

   • Newest class with excellent efficacy and safety profile 2, 3
   • Strong recommendation for skin and nail disease 2

4. IL-12/23 inhibitors:

   • Effective for both skin and joint manifestations 2
   • Strong recommendation for skin and nail disease 2

Small Molecule Inhibitors

• JAK inhibitors: Oral agents that block multiple cytokine pathways 2, 3
• TYK2 inhibitors: More selective JAK inhibition with potentially improved safety profile 3
• PDE4 inhibitors (apremilast): Oral agent with moderate efficacy but favorable safety profile 2, 1

Traditional Systemic Therapies

• Methotrexate: Still valuable, especially when combined with biologics 1
• Cyclosporine: Rapid control but limited to short-term use due to nephrotoxicity 1
• Acitretin: Oral retinoid, less effective as monotherapy but useful for pustular variants 1

Phototherapy Advances

• Narrowband UVB: First-line phototherapy option 1
• Targeted phototherapy: 308-nm excimer laser for localized lesions and resistant areas like scalp and skin folds 2
• PUVA: Option if narrowband UVB is inadequate 1

Treatment Algorithm Based on Disease Severity

For Mild Psoriasis (<10% BSA):

1. First-line: Combination of potent corticosteroid with vitamin D analog 1
2. Alternative options:
   • Calcineurin inhibitors for face/intertriginous areas 1
   • Tazarotene (avoid in pregnancy) 1
   • Targeted phototherapy for resistant areas 2

For Moderate-to-Severe Psoriasis (≥10% BSA):

1. First-line biologics:

   • TNF-α inhibitors (especially with joint involvement)
   • IL-17 inhibitors (superior skin clearance)
   • IL-23 inhibitors (excellent efficacy/safety balance)
   • IL-12/23 inhibitors 2, 1

2. Oral agents:

   • JAK/TYK2 inhibitors
   • PDE4 inhibitors
   • Traditional systemics (methotrexate, cyclosporine, acitretin) 1, 3

3. Phototherapy options:

   • Narrowband UVB
   • PUVA 1

Emerging Therapies in Clinical Development

• Oral IL-23 receptor inhibitors: Potential for robust safety profiles 3
• Oral IL-17A inhibitors: Effective but with potential side effects 3
• RORγT inhibitors: Target Th17 cell differentiation 3
• Nanobody products: Smaller antibody fragments with improved tissue penetration 3
• S1P1R antagonists: Modulate lymphocyte trafficking 3

Treatment Monitoring and Safety Considerations

• Evaluate topical therapy response after 4 weeks 1
• Limit potent corticosteroids to 4 weeks to minimize skin atrophy 1
• Monitor for specific adverse effects:
  • Biologics: infections, injection site reactions 4
  • JAK inhibitors: infections, laboratory abnormalities 3
  • Methotrexate: hepatotoxicity, bone marrow suppression 1

The treatment landscape for psoriasis has dramatically evolved with targeted biologics and small molecules offering unprecedented efficacy and safety for moderate-to-severe disease, while advances in topical therapies continue to improve outcomes for mild disease.