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Tuesday, August 19, 2025

Antipsoriatics


Introduction

Psoriasis is a chronic, immune-mediated, inflammatory skin disorder characterized by erythematous, scaly plaques, most commonly affecting the scalp, elbows, knees, and lower back. It is associated with systemic inflammation and comorbidities such as psoriatic arthritis, metabolic syndrome, and cardiovascular disease.

Antipsoriatics refer to the diverse group of medications used to suppress symptoms, control skin lesions, reduce inflammation, and prevent long-term complications. They range from topical therapies (first-line in mild disease) to systemic immunomodulators and biologics for moderate-to-severe cases.

Classification of Antipsoriatic Agents

1. Topical Antipsoriatics

  • Corticosteroids (e.g., hydrocortisone, betamethasone, clobetasol)

  • Vitamin D analogues (calcipotriol, calcitriol, tacalcitol)

  • Coal tar preparations

  • Dithranol (anthralin)

  • Keratolytics (salicylic acid, urea)

  • Calcineurin inhibitors (tacrolimus, pimecrolimus – off-label use)

  • Tazarotene (topical retinoid)

2. Phototherapy (Topical/Adjunctive)

  • Narrowband UVB (NB-UVB)

  • PUVA (Psoralen + UVA): Psoralens such as methoxsalen (8-MOP) are used with UVA exposure.

3. Systemic Non-Biologic Antipsoriatics

  • Methotrexate (antimetabolite)

  • Cyclosporine (calcineurin inhibitor)

  • Acitretin (oral retinoid)

  • Apremilast (PDE-4 inhibitor)

4. Biologic Antipsoriatic Agents

a) TNF-α inhibitors

  • Etanercept

  • Infliximab

  • Adalimumab

  • Certolizumab pegol

b) IL-12/23 inhibitors

  • Ustekinumab

c) IL-17 inhibitors

  • Secukinumab

  • Ixekizumab

  • Brodalumab

d) IL-23 inhibitors

  • Guselkumab

  • Tildrakizumab

  • Risankizumab

Mechanisms of Action

  • Topical corticosteroids: Reduce inflammation via suppression of pro-inflammatory cytokines and vasoconstriction.

  • Vitamin D analogues: Regulate keratinocyte proliferation and differentiation, modulate T-cell activity.

  • Coal tar and dithranol: Slow epidermal proliferation, anti-inflammatory effect.

  • Methotrexate: Folate antagonist; reduces lymphocyte proliferation and cytokine release.

  • Cyclosporine: Inhibits calcineurin, reducing T-cell activation and cytokine release.

  • Acitretin: Normalizes keratinocyte differentiation, has anti-inflammatory activity.

  • Apremilast: Inhibits PDE-4, increasing cAMP levels, reducing production of TNF-α, IL-23, IL-17.

  • Biologics: Target specific immune mediators (e.g., TNF-α, IL-12, IL-23, IL-17) critical in psoriasis pathogenesis.

Clinical Uses

  • Mild psoriasis (<5% body surface area involvement): Topical therapy (corticosteroids, vitamin D analogues).

  • Moderate psoriasis: Phototherapy, systemic non-biologics (methotrexate, acitretin, apremilast).

  • Severe psoriasis (>10% BSA or disabling disease): Biologics, cyclosporine, methotrexate.

  • Psoriatic arthritis: Methotrexate, apremilast, TNF inhibitors, IL-17/23 inhibitors.

  • Scalp psoriasis: Topical corticosteroids, coal tar shampoos, salicylic acid.

  • Nail psoriasis: Biologics (ustekinumab, secukinumab, adalimumab), methotrexate.

Dosage Examples

  • Topical corticosteroids: Clobetasol propionate 0.05% cream/ointment twice daily; betamethasone dipropionate 0.05%.

  • Calcipotriol: 50 µg/g ointment, applied twice daily.

  • Methotrexate: 7.5–25 mg orally or subcutaneously once weekly (with folic acid supplementation).

  • Cyclosporine: 2.5–5 mg/kg/day orally, divided doses.

  • Acitretin: 10–50 mg orally daily.

  • Apremilast: 30 mg orally twice daily after dose titration.

  • Etanercept: 50 mg subcutaneously once weekly.

  • Adalimumab: 80 mg SC loading dose, followed by 40 mg every 2 weeks.

  • Ustekinumab: 45–90 mg SC at weeks 0 and 4, then every 12 weeks.

  • Secukinumab: 300 mg SC weekly for 5 weeks, then monthly.

  • Guselkumab: 100 mg SC at weeks 0 and 4, then every 8 weeks.

Contraindications

  • Methotrexate: Pregnancy, liver disease, alcohol abuse, bone marrow suppression.

  • Cyclosporine: Renal impairment, uncontrolled hypertension, malignancy.

  • Acitretin: Teratogenic (contraindicated in pregnancy and women planning conception within 3 years of stopping).

  • Biologics: Active infections, untreated latent TB, hepatitis B reactivation risk.

  • Topical corticosteroids: Avoid prolonged use on face and intertriginous areas (risk of skin atrophy).

Adverse Effects

Topical therapies

  • Corticosteroids: Skin atrophy, telangiectasia, striae, tachyphylaxis.

  • Vitamin D analogues: Irritation, hypercalcemia (rare with topical use).

  • Coal tar/dithranol: Skin staining, irritation.

Systemic therapies

  • Methotrexate: Hepatotoxicity, pulmonary fibrosis, myelosuppression.

  • Cyclosporine: Nephrotoxicity, hypertension, hypertrichosis, gum hypertrophy.

  • Acitretin: Dry skin, mucous membranes, hyperlipidemia, teratogenicity.

  • Apremilast: GI upset, depression, weight loss.

Biologics

  • TNF inhibitors: Increased risk of infections (TB, hepatitis B, fungal), demyelinating disease, lupus-like syndrome.

  • IL-17 inhibitors: Candida infections, inflammatory bowel disease exacerbation.

  • IL-12/23 and IL-23 inhibitors: Risk of infections, nasopharyngitis.

  • Clozapine (rarely used in psoriasis but relevant in comorbidity): Agranulocytosis.

Precautions

  • Screen for infections before systemic immunosuppressive or biologic therapy (TB, hepatitis B/C, HIV).

  • Vaccinations: Avoid live vaccines while on biologics or immunosuppressants.

  • Laboratory monitoring:

    • Methotrexate: CBC, liver function, renal function.

    • Cyclosporine: Blood pressure, renal function, electrolytes.

    • Acitretin: Lipids, liver function.

    • Biologics: Regular infection screening.

  • Pregnancy precautions: Methotrexate and acitretin are teratogenic; biologics are relatively safer but require risk-benefit assessment.

Drug Interactions

  • Methotrexate: Increased toxicity with NSAIDs, sulfonamides, trimethoprim.

  • Cyclosporine: Metabolized by CYP3A4; interactions with macrolides, azoles, grapefruit juice (increase toxicity).

  • Acitretin: Contraindicated with alcohol (forms etretinate, which has prolonged half-life).

  • Apremilast: Reduced efficacy with strong CYP450 inducers (rifampin, carbamazepine, phenytoin).

  • Biologics: Should not be combined with other biologics or strong immunosuppressants due to infection risk.

Comparative Efficacy

  • Topical corticosteroids and vitamin D analogues: First-line for mild psoriasis.

  • Methotrexate: Standard systemic agent for moderate to severe psoriasis and psoriatic arthritis.

  • Cyclosporine: Rapid onset; effective but limited by nephrotoxicity (used short-term).

  • Acitretin: Best for pustular psoriasis and in combination with phototherapy.

  • Apremilast: Oral option for moderate psoriasis with good safety profile but less potent than biologics.

  • Biologics: Most effective for severe disease; high rates of PASI-75 and PASI-90 (Psoriasis Area and Severity Index improvement). IL-23 inhibitors (guselkumab, risankizumab) show the most durable responses.

Public Health Considerations

Psoriasis management has shifted from non-specific immunosuppression (methotrexate, cyclosporine) toward precision-targeted biologics. The challenge remains cost, accessibility, long-term safety, and balancing efficacy with the prevention of infection or malignancy risk.



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