What are the recommended oral biologics for treating moderate to severe psoriasis?

Oral Biologics for Psoriasis

Critical Clarification: No True "Oral Biologics" Exist

There are currently no oral biologic medications approved for psoriasis—all biologics are administered via subcutaneous injection or intravenous infusion. 1 The term "oral biologic" is a misnomer, as biologics are large protein molecules that would be degraded by the digestive system if taken orally. 2

Oral Systemic Treatment Options

Small Molecule Oral Agent

Apremilast (30 mg twice daily) is the only oral advanced therapy for moderate-to-severe psoriasis, but it is a phosphodiesterase-4 inhibitor, not a biologic. 3, 2

• Dosing: Titration starter pack over 2 weeks, then maintenance dose of 30 mg twice daily 3
• Efficacy: Approximately 33% of patients achieve PASI-75 at 16 weeks (compared to 5% with placebo) 3
• Key advantages: Oral administration, no need for laboratory monitoring, can be combined with methotrexate without drug interactions 3
• Important adverse effects: Diarrhea, nausea, weight loss (monitor weight regularly), and potential depression/suicidal ideation (use caution in patients with psychiatric history) 3
• Drug interactions: Avoid co-administration with strong CYP450 inducers like rifampin, which reduces apremilast exposure by 72% 3

Traditional Oral Systemic Agents

For patients requiring oral therapy, methotrexate remains the preferred first-line oral systemic agent according to established guidelines. 4

• Methotrexate: Initial dose 0.2 mg/kg body weight, maintenance 15 mg weekly initially, maximum 25-30 mg weekly 4
• Cyclosporine: 2.5-5 mg/kg daily, with response in approximately 3 weeks; requires monitoring of blood pressure and serum creatinine every 2 weeks for first 3 months 4
• Acitretin: Starting dose 0.75 mg/kg/day, maintenance titrated to 0.5 mg/kg/day; requires absolute contraception for at least 1 month before, during, and for at least 2 years after stopping treatment 4

Injectable Biologic Recommendations for Moderate-to-Severe Psoriasis

If you are seeking the most effective systemic therapy regardless of route, biologics administered by injection represent the gold standard for moderate-to-severe psoriasis. 5, 2

First-Line Injectable Biologics (Ranked by Efficacy)

The highest efficacy biologics based on network meta-analysis are: 6

1. Infliximab (IV infusion): 5 mg/kg at weeks 0,2,6, then every 8 weeks; achieves PASI 90 in the highest proportion of patients (RR 50.19 vs placebo) 1, 6

2. Bimekizumab (SC injection): Anti-IL17 agent with PASI 90 achievement (RR 30.27 vs placebo) 6

3. Ixekizumab (SC injection): Anti-IL17 agent with PASI 90 achievement (RR 30.19 vs placebo) 6

4. Risankizumab (SC injection): Anti-IL23 agent with PASI 90 achievement (RR 28.75 vs placebo) 6

Practical First-Line Choice for Most Patients

Ustekinumab (anti-IL12/23) is recommended as first-line therapy due to superior efficacy, favorable safety profile, and excellent drug survival rates. 5

• Dosing: 45 mg SC at weeks 0,4, then every 12 weeks for patients ≤100 kg; 90 mg SC at weeks 0,4, then every 12 weeks for patients >100 kg 5
• Dose escalation: Consider increasing to every 8 weeks for inadequate responders 5
• Special advantage: Effective for both psoriasis and Crohn's disease, making it optimal for patients with both conditions 7

Alternative Injectable Options

TNF-alpha inhibitors (adalimumab, etanercept) are alternative first-line options: 5

• Adalimumab: 80 mg at week 0, then 40 mg every 2 weeks; can increase to 40 mg weekly for better control 1
• Etanercept: 50 mg twice weekly for 12 weeks, then 50 mg weekly 1

Safety Considerations Across All Systemic Therapies

• Screen for tuberculosis and other infections before initiating any biologic therapy 5
• Methotrexate shows significantly lower risk of serious adverse events compared to most biologics, though based on low event numbers 6
• Avoid IL-17 inhibitors in patients with inflammatory bowel disease or at risk for it, as they may cause paradoxical worsening 7
• Apremilast may cause weight loss; monitor weight regularly and consider discontinuation if clinically significant unexplained weight loss occurs 3

Common Pitfall to Avoid

Do not prescribe systemic corticosteroids for psoriasis management except in three rare specific conditions—withdrawal precipitates erythrodermic or generalized pustular psoriasis. 4 This is a critical safety warning that is frequently overlooked in clinical practice.