Psoriasis Pharmacotherapy

Psoriasis pharmacotherapy covers topical agents, phototherapy, conventional systemic drugs, small molecules and biologics, chosen by extent, site, joint involvement, comorbidity, pregnancy plans, infection risk and access. Chronic plaque psoriasis is driven by the interleukin-23 and interleukin-17 axis, with tumour necrosis factor amplifying inflammation. Most patients need only topical therapy; about one in five needs systemic treatment.

Mechanism. Topical steroids reduce inflammation; vitamin D analogues (calcipotriol) bind the vitamin D receptor and normalise keratinocyte growth; dithranol and coal tar are antiproliferative. Methotrexate inhibits dihydrofolate reductase and lymphocyte proliferation; ciclosporin blocks calcineurin and T-cell activation; acitretin normalises keratinisation. Apremilast inhibits phosphodiesterase 4. Biologics block tumour necrosis factor, interleukin-17A (and F), interleukin-23 (p19) or interleukin-12 and 23 (p40).

Pharmacokinetics. Methotrexate is given once weekly; folic acid reduces toxicity. Ciclosporin is a CYP3A4 and P-glycoprotein substrate with wide interactions. Biologics are given by injection with half-lives of 2 to 4 weeks (infliximab by infusion); antidrug antibodies reduce response, particularly with adalimumab and infliximab used alone.

Topical regimens.

• Plaques: potent steroid once daily for 2 to 4 weeks, or calcipotriol twice daily (maximum about 100 g weekly), or fixed calcipotriol with betamethasone once daily for up to 4 weeks, then calcipotriol alone with weekend steroid for maintenance.
• Face and flexures: mild steroid or tacrolimus ointment; avoid calcipotriol and tar on the face.
• Scalp: potent steroid or fixed combination in a gel or foam; salicylic acid or coconut oil compound to lift scale first.
• Thick scale: salicylic acid 2 to 5 percent; dithranol 0.1 to 2 percent short contact, increased weekly.

Systemic regimens.

• Methotrexate: test dose 5 to 7.5 mg once weekly, then 7.5 to 25 mg once weekly orally or subcutaneously; folic acid 5 mg once weekly on a different day. Response at 8 to 12 weeks.
• Ciclosporin: 2.5 mg/kg daily in two doses, increasing to 5 mg/kg daily; use for a maximum of 1 to 2 years; useful as rapid control of unstable or erythrodermic disease.
• Acitretin: 25 to 50 mg daily; best in pustular and erythrodermic forms and in HIV-associated disease; not first line for plaques alone; contraception rules apply.
• Apremilast: titrate 10 mg on day 1 to 30 mg twice daily by day 6; continue 30 mg twice daily.
• Adalimumab: 80 mg once, then 40 mg every 2 weeks from week 1. Etanercept: 50 mg twice weekly for 12 weeks, then once weekly. Infliximab: 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks.
• Secukinumab: 300 mg at weeks 0 to 4, then every 4 weeks. Ixekizumab: 160 mg once, then 80 mg at weeks 2, 4, 6, 8, 10 and 12, then every 4 weeks.
• Ustekinumab: 45 mg (90 mg if over 100 kg) at weeks 0 and 4, then every 12 weeks. Guselkumab: 100 mg at weeks 0 and 4, then every 8 weeks. Risankizumab: 150 mg at weeks 0 and 4, then every 12 weeks.

Selection. Biologics when disease is severe, involves face, nails, genitalia or palms, or fails or is unsuitable for two conventional systemic drugs or phototherapy.

Interleukin-17 and interleukin-23 inhibitors suit rapid, high response; tumour necrosis factor inhibitors suit joint disease and are cheaper; avoid interleukin-17 inhibitors in active inflammatory bowel disease. Psoriatic arthritis favours methotrexate, tumour necrosis factor or interleukin-17 inhibitors.

Pustular psoriasis: acitretin, ciclosporin, or infliximab; erythrodermic: ciclosporin or infliximab, with supportive care.

Screening before biologics. Tuberculosis (symptoms, chest imaging and interferon-gamma release assay or tuberculin test), hepatitis B and C, and HIV; treat latent tuberculosis before or with the start of a tumour necrosis factor inhibitor. Vaccinate against hepatitis B, influenza and pneumococcus first; avoid live vaccines on treatment.

Class risks.

• Methotrexate: nausea, mouth ulcers, marrow suppression, hepatotoxicity, pneumonitis, teratogenicity (stop 3 months before conception in men and women). Avoid with trimethoprim, high-dose aspirin or NSAIDs, and in renal impairment.
• Ciclosporin: hypertension, nephrotoxicity, tremor, gum overgrowth, hirsutism, skin cancer; avoid with nephrotoxic drugs, strong CYP3A4 inhibitors and inducers, and live vaccines.
• Acitretin: teratogenicity, hyperlipidaemia, hepatitis, cheilitis, alopecia.
• Apremilast: diarrhoea, nausea, weight loss, depression.
• Tumour necrosis factor inhibitors: serious infection, tuberculosis reactivation, demyelination, lupus-like syndrome, heart failure, paradoxical psoriasis.
• Interleukin-17 inhibitors: mucocutaneous candidiasis, inflammatory bowel disease flare; interleukin-23 inhibitors: upper respiratory infection, with fewer serious infections.
• Triggers to avoid or review: systemic steroids (rebound pustular psoriasis), lithium, beta blockers, antimalarials, abrupt withdrawal of potent steroids, streptococcal infection, HIV.

Monitoring.

• Methotrexate: full blood count, liver tests and creatinine every 2 weeks for 6 weeks, then every 3 months.
• Ciclosporin: blood pressure and creatinine every 2 weeks for 3 months, then monthly; reduce dose if creatinine rises 25 percent above baseline.
• Biologics: annual tuberculosis symptom review; liver tests and blood count at intervals; assess response at 12 to 16 weeks and stop if there is no meaningful response.

Special groups. Pregnancy: emollients, mild to potent steroids and phototherapy; certolizumab or adalimumab if needed; avoid methotrexate, acitretin and ciclosporin where possible. Children: topical steroids and calcipotriol; biologics specialist-led. Region: high background tuberculosis and hepatitis B in East Africa make screening and isoniazid prophylaxis part of every biologic plan; psoriasis in HIV is often severe and responds to antiretroviral therapy, acitretin and phototherapy; biologic cost and supply limit use.