What is the recommended treatment algorithm for plaque psoriasis in an adult patient without contraindications?

Treatment Algorithm for Plaque Psoriasis

For mild plaque psoriasis (<5% body surface area), start with once-daily combination calcipotriene/betamethasone dipropionate for 4 weeks; for moderate-to-severe disease (≥5% BSA), initiate biologic therapy with adalimumab (80 mg initial dose, 40 mg at week 1, then 40 mg every 2 weeks) as first-line systemic treatment. 1, 2

Disease Severity Classification & Treatment Selection

Mild Psoriasis (<5% BSA)

• Begin with fixed-combination calcipotriene/betamethasone dipropionate applied once daily for 4 weeks, which provides superior efficacy and fewer adverse effects than either agent alone 1
• For scalp involvement, use calcipotriene plus betamethasone dipropionate gel or clobetasol propionate 0.05% solution twice daily 1
• Ultrahigh-potency class 1 corticosteroids (clobetasol 0.05% or halobetasol 0.05%) achieve 58-92% clearance of thick, chronic plaques 1
• Long-term maintenance: apply vitamin D analogues twice daily on weekdays combined with high-potency corticosteroids twice daily on weekends 1
• Critical pitfall to avoid: Never combine salicylic acid with calcipotriene—the acidic pH inactivates calcipotriene and eliminates its efficacy 1

Moderate-to-Severe Psoriasis (≥5% BSA or High-Impact Sites)

• Moderate-to-severe disease is defined as ≥5% BSA, or PASI ≥10 with DLQI >10, or involvement of high-impact sites (face, scalp, palms/soles, nails, genitalia) causing pain, bleeding, or intractable pruritus regardless of BSA 1, 2
• Patients are eligible for biologics when they meet PASI ≥10 AND DLQI >10, and have failed, have contraindications to, or are intolerant of at least one conventional systemic therapy 2, 3

First-Line Biologic Therapy Algorithm

Preferred First-Line Agent: Adalimumab

• Dosing: 80 mg subcutaneous on Day 1, then 40 mg at Week 1, followed by 40 mg every 2 weeks 1, 2, 3
• Efficacy: Achieves PASI 75 in 71% of patients at week 16 (versus 7% with placebo) 1, 2
• Assess response at 16 weeks; treatment success is defined as PASI 75 or PASI 50 with DLQI improvement >5 points 2, 3

Alternative First-Line Agents

Infliximab (highest efficacy but requires IV administration):

• Dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 1, 2
• Efficacy: Achieves PASI 75 in 79-80% of patients by week 10 1, 2
• Mandatory co-administration: Add methotrexate to reduce immunogenicity—without it, approximately 19% develop anti-infliximab antibodies 1, 2
• Critical pitfall: Never extend infliximab intervals beyond 8 weeks 2

Etanercept (lower efficacy but well-established safety):

• Dosing: 50 mg subcutaneous twice weekly for 12 weeks, then 50 mg once weekly 1, 2
• Efficacy: Achieves PASI 75 in 48-66% at week 12 1, 2
• Assess response at 12 weeks 2

Newer high-efficacy biologics (for severe disease with ≥10% BSA or PASI ≥10):

• Bimekizumab, ixekizumab, or risankizumab achieve PASI 90 in 80-84% of patients (RR ≈30 versus placebo) 1
• These agents represent the highest-efficacy options when rapid and extensive clearance is the priority 1

Site-Specific Treatment Recommendations

Palmoplantar Psoriasis

• Ustekinumab 90 mg achieves complete clearance in 67% of patients (versus 9% with 45 mg dose) 4, 1
• Adalimumab is also strongly recommended regardless of overall skin disease severity 2, 3

Nail Psoriasis

• Ustekinumab leads to median 100% improvement in NAPSI scores by week 40, with 44.7% achieving full nail clearance 1
• Adalimumab and etanercept are also recommended (Strength A) 2

Psoriatic Arthritis (Any Severity)

• Adalimumab is the preferred agent because it treats both skin and joint symptoms and inhibits radiographic joint damage 1, 2, 3
• Infliximab is an alternative that also inhibits radiographically detected joint damage 1
• Biologics are indicated for psoriatic arthritis regardless of skin disease extent 2

Ustekinumab Dosing & Optimization

• Standard dosing: 45 mg subcutaneous at weeks 0,4, then every 12 weeks for patients ≤100 kg; 90 mg at the same schedule for patients >100 kg 4, 1
• Dose escalation for inadequate response: Increase to 90 mg or shorten interval to every 8 weeks 4, 1
• Combination strategies: Adding methotrexate or acitretin may augment efficacy 4, 1

Combination Therapy to Enhance Biologic Efficacy

• Add high-potency topical corticosteroid to etanercept for 12 weeks (Level I evidence, Strength A) 1, 2
• Add calcipotriene/betamethasone dipropionate to adalimumab for 16 weeks to accelerate clearance (Strength B) 1, 2
• All topical corticosteroids can be combined with any biologic (Strength C) 1
• Methotrexate combinations with etanercept, adalimumab, and infliximab reduce immunogenicity and prevent antibody formation (Strength B) 2

Safety Monitoring & Mandatory Screening

Tuberculosis Screening (Required Before All Biologics)

• Perform PPD skin test or interferon-γ release assay before initiating any biologic; treat latent TB before starting therapy 1
• Ongoing monitoring for active TB is required throughout treatment, even after a negative baseline test 1, 3

Traditional Systemic Agents (When Biologics Are Not Available)

Cyclosporine (for severe, recalcitrant disease):

• Dosing: 2.5-5.0 mg/kg/day in two divided doses 1
• Efficacy: At 5 mg/kg/day, 65% achieve clear/almost clear status after 8 weeks 1
• Duration: Short-term courses of 3-4 months preferred; US approval permits up to 1 year 1
• Monitoring: Blood pressure & serum creatinine every 2 weeks for 3 months, then monthly; monthly CBC, liver enzymes, lipids, electrolytes 1
• Avoid grapefruit juice (pharmacokinetic interaction) 1

Methotrexate (traditional first-line systemic):

• May be combined with topical calcipotriene (Level I evidence, Strength A) 1
• Associated with lower incidence of serious adverse events compared with most biologics, though evidence is of very low certainty 1

Critical Pitfalls to Avoid

• Never use systemic corticosteroids (prednisone) for psoriasis—they have poor long-term efficacy and cause severe rebound flares upon discontinuation 2, 3
• Do not delay biologics in patients with >5% BSA involvement who meet treatment criteria 2, 3
• Failure to respond to one TNF-α inhibitor does not preclude successful response to a different TNF-α inhibitor, although overall efficacy may be reduced 1
• Failure of any biologic does not preclude successful response to ustekinumab 1
• When retreating after a drug holiday >3-4 half-lives, repeat loading doses; a minority may not recapture prior response magnitude 1

Adjunctive Non-Pharmacologic Therapies

• Regular moisturizers 1-3 times daily reduce itching, scaling, and desquamation 1
• Stress-reduction techniques (mindfulness meditation, cognitive-behavioral therapy, guided imagery) improve psoriasis severity 1
• Narrowband UV-B phototherapy is the most commonly prescribed light therapy for plaque psoriasis 5
• Gluten-free diet is recommended only for patients with confirmed celiac disease, typically trialed for 3 months 1
• Oral vitamin D, oral zinc, and cannabis/cannabinoids do not demonstrate clinically meaningful improvement 1