A 38-year-old man presents with a 5-year history of chronic plaque psoriasis affecting 12% of his body surface area. He has failed topical corticosteroids and coal tar therapy. Which is the drug of choice for systemic treatment in this patient?

Explanation

## First-Line Systemic Agent for Moderate-to-Severe Psoriasis **Key Point:** Methotrexate is the gold-standard first-line systemic agent for moderate-to-severe plaque psoriasis affecting >10% BSA or causing significant functional impairment. ### Mechanism of Action Methotrexate inhibits dihydrofolate reductase, reducing DNA synthesis and cell proliferation. It also suppresses T-cell activation and TNF-α production, addressing both the proliferative and inflammatory components of psoriasis. ### Dosing & Monitoring - **Initial dose:** 10–15 mg once weekly (oral or IM) - **Escalation:** Increase by 2.5–5 mg weekly up to 25 mg/week based on response - **Monitoring:** CBC, LFTs, renal function at baseline, then every 8–12 weeks - **Contraindications:** Pregnancy, renal/hepatic impairment, active infection ### Efficacy Timeline - Response typically seen within 4–8 weeks - Maximum benefit at 12–16 weeks - Efficacy rate: 60–70% achieve >75% improvement in PASI **High-Yield:** Methotrexate is preferred over acitretin and cyclosporine as first-line because it has the best long-term safety profile, is cost-effective, and can be used for extended periods with appropriate monitoring. It is the standard of care in most guidelines including Indian dermatology consensus. ### Comparison with Other Systemic Agents | Agent | First-Line? | Onset | Key Advantage | Key Limitation | |-------|-----------|-------|---------------|----------------| | **Methotrexate** | Yes | 4–8 weeks | Long-term safety, cost-effective, well-studied | Teratogenic, hepatotoxicity risk | | **Acitretin** | No (2nd-line) | 2–4 weeks | Faster onset, good for pustular psoriasis | Teratogenic (category X), lipid elevation | | **Cyclosporine** | No (2nd-line) | 2–4 weeks | Rapid response | Nephrotoxicity, hypertension, expensive | | **Biologics (TNF-α inhibitors)** | No (3rd-line) | 2–4 weeks | Highest efficacy, well-tolerated | Very expensive, TB reactivation risk | **Clinical Pearl:** Methotrexate can be combined with topical agents and phototherapy for enhanced response. Folic acid supplementation (5 mg daily on non-MTX days) is mandatory to reduce toxicity. **Tip:** In NEET PG exams, when a moderate-to-severe psoriasis patient has failed topical therapy, always think methotrexate first unless there is a specific contraindication (pregnancy, renal disease, hepatic disease) or the question specifies a special scenario (e.g., pustular psoriasis → acitretin; acute flare → cyclosporine).