What are the latest treatment guidelines for a patient with moderate to severe psoriasis?

Latest Guidelines for Treatment of Moderate to Severe Psoriasis

For moderate to severe psoriasis, biologic therapy (TNF-α inhibitors, IL-17 inhibitors, or IL-23 inhibitors) is recommended as first-line systemic treatment, with topical calcipotriene/betamethasone dipropionate combination used as adjunctive therapy for residual plaques. 1

Disease Severity Classification

Moderate to severe psoriasis is defined as body surface area (BSA) >10% or PASI score ≥10. 2

• BSA measurement is recommended as an important measure to risk stratify patients for future comorbidities and assess treatment response 2
• Patients with moderate to severe disease require systemic therapy and should be under continuing supervision of a consultant dermatologist 3

First-Line Systemic Treatment: Biologic Therapy

Biologic agents are the preferred first-line systemic treatment for moderate to severe psoriasis, with newer biologics (IL-17 and IL-23 inhibitors) showing higher efficacy than TNF inhibitors. 1, 3

Recommended Biologic Options (in order of preference):

IL-12/23 Inhibitors:

• Ustekinumab: 45 mg subcutaneously at weeks 0,4, then every 12 weeks for patients ≤100 kg; 90 mg for patients >100 kg 4
• Superior efficacy, favorable safety profile, and excellent drug survival rates 4

TNF-α Inhibitors:

• Adalimumab: 80 mg initial dose, then 40 mg every 2 weeks starting one week after initial dose 5
• Can be increased to 40 mg weekly for better control 4
• 80% of patients achieve PASI-75 by week 16 3
• Infliximab is also recommended as first-line therapy 2, 1

IL-17 and IL-23 Inhibitors:

• Secukinumab and other IL-17/IL-23 inhibitors are recommended options 1
• Avoid IL-17 inhibitors in patients with inflammatory bowel disease or at risk for it, as they may cause paradoxical worsening 4

Critical Safety Requirements:

• Screen for tuberculosis and other infections before initiating any biologic therapy 4, 5
• Monitor all patients for active TB during treatment, even if initial latent TB test is negative 5
• Continue biologic therapy indefinitely for sustained disease control 1
• Avoid interrupted biologic therapy due to increased risk of infusion reactions, antibody formation, and poorer disease control 3

Alternative Systemic Agents (When Biologics Are Not Appropriate)

Traditional oral systemic agents can be used when biologics are contraindicated or unavailable:

Methotrexate:

• Starting dose: 7.5 mg weekly, increasing to maximum 25-30 mg weekly as tolerated 3, 4
• Initial dose can be 0.2 mg/kg body weight 4
• Monitor liver function; avoid in patients with hepatic disease 2
• Male patients should avoid conception until 3 months after discontinuation due to effects on spermatogenesis 2

Cyclosporine:

• For erythrodermic psoriasis: 3-5 mg/kg/day is the preferred initial treatment due to rapid onset of action 1
• For stable disease: 2.5-5 mg/kg daily 4
• Generally only a short 3-4 month "interventional" course is indicated 2, 1
• Monitor blood pressure and serum creatinine every 2 weeks for first 3 months 4
• Avoid in patients with renal disease or hypertension 2

Acitretin:

• Starting dose: 0.75 mg/kg/day, maintenance 0.5 mg/kg/day 4
• Absolutely contraindicated in women of childbearing potential due to teratogenic effects; requires contraception for at least 2 years after stopping treatment 2, 1, 4
• Slow onset of action limits usefulness in patients requiring rapid response 2

Essential Adjunctive Topical Therapy

Even with systemic treatment, topical therapy should be added to accelerate clearance and target residual plaques:

• Calcipotriene 0.005%/betamethasone dipropionate 0.064% combination: Apply once daily 1, 3
• This combination achieves 69-74% clear or almost clear status versus 27% with vehicle control 3
• Adding ultrahigh potency (class 1) topical corticosteroid for 12 weeks to biologics accelerates clearance 3
• No serious adverse events observed over 52 weeks with this combination 3

Phototherapy as Alternative First-Line Option

Narrowband UVB 2-3 times weekly is an effective option for patients who can commit to the time requirement:

• Effective in the majority of patients, cost-effective, lacks systemic toxicities 2, 1
• First-line for pregnant women with moderate to severe disease 2
• Requires significant time commitment (2-3 times weekly), which can lead to work-related difficulties 2
• Combination with methotrexate or acitretin produces synergistic effects, allowing reduced UV doses 2

Treatment Algorithm for Inadequate Response

If inadequate response after 12-16 weeks of biologic therapy, switch to an alternative biologic rather than adding a second biologic. 1

• Re-treatment response rates are lower if adequate response is lost after stopping biologics, suggesting continuous therapy is preferable 3
• Maintaining topical therapy during systemic treatment can prevent quick relapse when systemics are discontinued 3

Special Considerations

Psoriatic Arthritis:

• Biologic therapy is mandatory regardless of skin BSA involvement 1

Erythrodermic Psoriasis:

• Cyclosporine 4 mg/kg/day is the preferred initial treatment 2, 1
• Appropriate wet dressings with mid-potency topical steroids 2
• Attention to fluid balance with control of ankle edema 2
• Rule out sepsis with blood cultures 2

Pregnancy:

• Narrowband UVB should be considered first-line for pregnant women with moderate to severe disease 2

Common Pitfalls to Avoid

• Do not use topical therapy alone for severe whole-body psoriasis—this is inadequate and delays appropriate systemic treatment 3
• Do not interrupt biologic therapy once started, as this increases antibody formation and reduces efficacy 3, 4
• Do not assume treatment failure is due to "tachyphylaxis"—it is usually due to poor adherence 3
• Do not use acitretin in women of childbearing potential 2, 1, 4
• Do not use IL-17 inhibitors in patients with inflammatory bowel disease 4