What are the treatment options for moderate to severe psoriasis?

Treatment Options for Moderate to Severe Psoriasis

For moderate to severe plaque psoriasis, initiate biologic therapy with ustekinumab (IL-12/23 inhibitor) as first-line treatment, dosed at 45 mg subcutaneously at weeks 0,4, then every 12 weeks for patients ≤100 kg, or 90 mg for patients >100 kg, due to superior efficacy, favorable safety profile, and excellent drug survival rates. 1, 2

First-Line Biologic Options

Preferred: Ustekinumab (IL-12/23 Inhibitor)

• Ustekinumab is the recommended first-line biologic based on the most recent guideline evidence prioritizing long-term outcomes 1
• Dosing: 45 mg SC at weeks 0,4, then every 12 weeks for patients ≤100 kg 1, 2
• Dosing: 90 mg SC at weeks 0,4, then every 12 weeks for patients >100 kg 1, 2
• For inadequate responders, increase frequency to every 8 weeks 1
• Effective for difficult-to-treat areas including scalp, nails, and palmoplantar regions 1

Alternative First-Line: TNF Inhibitors

Adalimumab:

• Dosing: 80 mg at week 0, then 40 mg every other week 1, 2, 3
• Can increase to 40 mg weekly for better disease control 2, 3
• FDA-approved for moderate to severe chronic plaque psoriasis 3

Infliximab:

• Dosing: 5 mg/kg IV at weeks 0,2,6, then every 8 weeks 4, 1
• Can increase frequency to every 4 weeks or dose up to 10 mg/kg for better control 4
• Particularly effective for rapid response in severe cases 4
• Also inhibits radiographic joint damage in psoriatic arthritis 4

Etanercept:

• Dosing: 50 mg SC twice weekly for 12 weeks, then 50 mg weekly 4, 1, 2
• FDA-approved for pediatric patients ≥4 years of age 1
• Effective for palmoplantar, nail, and scalp psoriasis 4

Phototherapy as Alternative First-Line

• Narrowband UVB (NB-UVB) is first-line for pregnant women with moderate to severe psoriasis, avoiding systemic immunosuppression 4
• Phototherapy includes UVB/NB-UVB, oral PUVA, or bath PUVA, with or without acitretin 4
• Requires 2-3 times weekly treatments, which may impact quality of life and work 4
• Critical pitfall: Avoid aggressive immunosuppression following extensive PUVA therapy due to increased melanoma and non-melanoma skin cancer risk 4

Systemic Non-Biologic Options

Cyclosporine (Rapid-Acting for Severe Cases)

• Use cyclosporine 3-5 mg/kg/day for erythrodermic psoriasis or systemically ill patients requiring rapid response 4, 5, 2
• Limit to short 3-4 month "interventional" courses 4, 5
• Monitor blood pressure and serum creatinine every 2 weeks for first 3 months 2
• Provides dramatic improvement within 2-3 weeks in erythrodermic cases 4

Methotrexate

• Dosing: Initial 0.2 mg/kg body weight, maintenance 15 mg weekly initially, maximum 25-30 mg weekly 2
• Preferred first-line oral systemic agent when oral therapy is required 2
• Subcutaneous administration bypasses liver and may provide better response 4
• Avoid conception in males until 3 months after discontinuation due to effects on spermatogenesis 4

Acitretin

• Dosing: Starting 0.75 mg/kg/day, maintenance titrated to 0.5 mg/kg/day 2
• Absolutely contraindicated in women of childbearing potential - requires contraception for at least 1 month before, during, and for at least 2 years after stopping 2, 6
• Slower onset of action limits usefulness in acute severe cases 4, 5
• Effective for generalized pustular psoriasis, palmoplantar pustulosis, and erythrodermic psoriasis 6
• All patients experience mucocutaneous adverse effects (dry lips, hair loss, skin peeling) 7

Combination Therapy Strategies

Biologics + Topicals

• Combine biologics with high-potency corticosteroids with or without vitamin D analogues to augment efficacy 4, 1
• Methotrexate can be combined with biologics for enhanced response 4, 1
• Acitretin may be combined with biologics, particularly useful in multi-drug refractory cases 4, 1

Phototherapy Combinations

• Methotrexate combined with BB-UVB, NB-UVB, or PUVA produces synergistic effects, allowing reduced treatment duration and lower cumulative UV doses 4
• Acitretin combined with NB-UVB or PUVA increases response rates and decreases total UV exposure 4
• Etanercept 50 mg twice weekly plus NB-UVB thrice weekly achieved 85% PASI-75 response at 12 weeks 4
• Apply vitamin D analogues after phototherapy to avoid inactivation 5

Special Populations and Considerations

Psoriatic Arthritis

• TNF inhibitors (adalimumab, etanercept, infliximab) or ustekinumab are recommended 4, 1
• All three TNF inhibitors are equally effective for peripheral arthritis and inhibiting radiographic progression 4
• Infliximab recommended for spinal disease/axial involvement 4

Pediatric Patients

• Etanercept FDA-approved for ages ≥4 years 1
• Ustekinumab FDA-approved for ages ≥12 years 1
• Acitretin showed moderate effectiveness in children with 44.4% achieving ≥75% improvement, though mucocutaneous effects occurred universally 8

Erythrodermic Psoriasis Algorithm

First-line options (in order of preference for rapid response):

1. Cyclosporine 3-5 mg/kg/day for 3-4 months 4, 5
2. Infliximab 4
3. Adalimumab 4
4. Ustekinumab 4

Second-line combinations:

• Acitretin + cyclosporine 4
• Acitretin + TNF blocker 4
• Cyclosporine + methotrexate 4
• Methotrexate + TNF blocker 4

Supportive care: Mid-potency topical steroids with wet dressings, attention to fluid balance and ankle edema control 4

Critical Safety Considerations

Pre-Treatment Screening

• Screen for tuberculosis and other infections before initiating any biologic therapy 1, 2
• Ensure patients are up-to-date on vaccinations before starting therapy 1
• Test for latent TB; if positive, start TB treatment prior to initiating biologics 3

Monitoring and Contraindications

• Discontinue biologics if serious infection or sepsis develops 3
• Monitor all patients for active TB during treatment, even if initial latent TB test negative 3
• Avoid IL-17 inhibitors in patients with inflammatory bowel disease or at risk, as they may cause paradoxical worsening 2
• Regular follow-up necessary to assess for adverse events 1

Black Box Warnings for TNF Inhibitors

• Increased risk of serious infections leading to hospitalization or death, including tuberculosis, bacterial sepsis, and invasive fungal infections 3
• Lymphoma and other malignancies reported, some fatal, particularly in children and adolescents 3
• Post-marketing cases of hepatosplenic T-cell lymphoma in adolescents and young adults with inflammatory bowel disease 3

Key Pitfalls to Avoid

• Never use systemic corticosteroids for psoriasis - they should generally be avoided 5
• Do not combine salicylic acid with calcipotriene simultaneously - acidic pH inactivates calcipotriene 5
• Avoid extensive PUVA followed by aggressive immunosuppression due to cumulative skin cancer risk 4
• Do not use acitretin in women of childbearing potential without absolute contraception for 2+ years after stopping 2, 6
• Limit cyclosporine to <12 consecutive months due to cumulative toxicity concerns 4