What is the best treatment for a patient with plaque psoriasis, considering severity and potential comorbidities like psoriatic arthritis?

Best Treatment for Plaque Psoriasis

For mild plaque psoriasis (<5% body surface area), start with combination calcipotriene plus betamethasone dipropionate applied once daily for 4 weeks, which provides superior efficacy and safety compared to monotherapy. 1 For moderate-to-severe disease (≥5% BSA), initiate biologic therapy with adalimumab or infliximab as first-line systemic treatment. 1

Treatment Algorithm Based on Disease Severity

Mild Psoriasis (<5% BSA)

First-line topical therapy:

• Use combination calcipotriene/betamethasone dipropionate as a single product once daily for 4 weeks, achieving maximal improvement in the majority of patients 1
• This combination is more effective than either agent alone because vitamin D analogues counter epidermal hyperproliferation while corticosteroids suppress inflammation 2, 3
• The combination also reduces adverse effects: vitamin D restores epidermal barrier function impaired by corticosteroids, while corticosteroids reduce perilesional irritation from vitamin D 2

Maintenance regimens after initial 4 weeks:

• Apply vitamin D analogues twice daily on weekdays combined with high-potency corticosteroids twice daily on weekends 1
• Alternative: morning high-potency corticosteroids with evening vitamin D analogues 1
• Long-term use up to 52 weeks is safe and recommended 1

For scalp psoriasis specifically:

• Use calcipotriene foam or calcipotriene plus betamethasone dipropionate gel for 4-12 weeks 1
• Generic clobetasol propionate 0.05% solution twice daily is highly effective and among the least expensive options 1

Moderate-to-Severe Psoriasis (≥5% BSA)

First-line biologic therapy options in order of preference:

1. Adalimumab (preferred TNF inhibitor):

   • Dosing: 80 mg initial dose, then 40 mg one week later, then 40 mg every 2 weeks 1, 4
   • Achieves PASI 75 in 71% of patients at week 16 versus 7% with placebo 1
   • FDA-approved for plaque psoriasis 4

2. Infliximab (alternative first-line):

   • Dosing: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks 5, 1
   • Achieves PASI 75 in 80% of patients 1
   • Can increase frequency to every 4 weeks or dose up to 10 mg/kg for better control 5

3. Etanercept (alternative option):

   • Dosing: 50 mg subcutaneously twice weekly for 12 weeks, then 50 mg once weekly 5, 1
   • Achieves PASI 75 in 48-66% at week 12 5, 1
   • FDA-approved for pediatric patients ≥4 years old 5

Combination strategies to augment biologic efficacy:

• Add high-potency topical corticosteroids with or without vitamin D analogues 5, 1
• Combine with methotrexate (may augment efficacy) 5
• Combine with acitretin (may augment efficacy) 5

Special Clinical Scenarios

Psoriatic Arthritis (Any Severity)

Adalimumab or infliximab are strongly recommended regardless of skin disease severity:

• Both treat skin and joint symptoms simultaneously 1
• Both inhibit radiographically detected joint damage 5, 1
• This is a critical indication to escalate to biologics even with limited skin involvement 1

Site-Specific Difficult Areas

For palmoplantar, nail, or scalp involvement:

• Infliximab can be used as monotherapy with strength B recommendation 5
• These areas often respond poorly to topicals alone and warrant systemic therapy 5

Symptomatic Limited Disease

Consider systemic or phototherapy even for <5% BSA if:

• Patient has pain, bleeding, or severe itching 1
• Quality of life is significantly impaired despite limited surface area 1

Critical Safety Considerations

Before initiating any biologic therapy:

• Screen for tuberculosis and other infections 4
• Ensure vaccinations are up-to-date (no live vaccines during treatment) 4
• Screen for hepatitis B 4
• Assess for history of malignancy, heart failure, or demyelinating disease 4

Black box warnings for TNF inhibitors:

• Increased risk of serious infections including TB reactivation 4
• Lymphoma and other malignancies, particularly hepatosplenic T-cell lymphoma in young males receiving concomitant azathioprine or 6-mercaptopurine 4
• Avoid combining TNF inhibitors with azathioprine or 6-MP when possible 4

Common Pitfalls to Avoid

Do not use systemic corticosteroids (prednisone):

• Not standard of care for psoriasis 6
• Poor long-term efficacy and significant safety concerns 6
• Can cause rebound flares upon discontinuation 6

Do not undertreate moderate-to-severe disease:

• Topicals alone are insufficient for >5% BSA involvement 5
• Biologics have high benefit-to-risk ratio and should not be delayed 5

Do not use acitretin in women of childbearing potential:

• FDA requires 3-year postdosing moratorium on pregnancy 5
• Additional concerns include hepatotoxicity and hypertriglyceridemia 5

Monitor for treatment failure indicators:

• If inadequate response to topicals after 4 weeks, escalate to phototherapy or biologics 1
• If inadequate response to biologics, consider dose escalation or combination therapy 5, 1