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Scaly skin diseases

Systemic therapy for psoriasis

Objectives

  • Describe use of systemic therapies for psoriasis.

Key points

Key points for students include:

  • Systemic therapy should be considered for those more than 10% to 20% body surface involvement, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis and more localized, recalcitrant psoriasis.
  • The PASI (Psoriasis Area and Severity Index) combines assessments on the percentage of body area affected, erythema, desquamation, and induration to produce a score ranging from 0 to 72.
  • Methotrexate is probably effective because of its anti-inflammatory effects.
  • Methotrexate is administered once weekly.
  • Adverse reactions of methotrexate include gastrointestinal effects, mouth ulceration, pulmonary fibrosis, bone marrow suppression and hepatic fibrosis.
  • Acitretin is an oral retinoid used to treat psoriasis and other disorders of keratinisation.
  • Adverse reactions of acitretin include teratogenicity, mucocutaneous effects, athralgias, myalgias, raised intracranial pressure, decreased night vision and hypertriglyceridaemia.
  • Cyiclosporin is a calcineurin inhibitor that inhibits T cell activation.
  • Adverse effects of cyiclosporin include nephrotoxicity, hypertension and induction of skin cancer.
  • Biologic agents used in psoriasis include etanercept, adalimumab, infliximab and ustekinumab. New compounds are under development.

Introduction

Patients are considered to have severe psoriasis if they have extensive plaques, psoriasis on exposed sites or resulting in functional impairment (e.g. on hands preventing work, or feet preventing walking). ‘Severity’ may depend on the patient’s age, cultural background and occupation. Systemic therapy should be considered for those more than 10% to 20% body surface involvement, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis and more localized, recalcitrant psoriasis.

PASI score

The PASI (Psoriasis Area and Severity Index) was set up as an attempt to assess the severity of psoriasis for clinical trials. The percentage of patients achieving a 50% or 75% reduction in PASI is used to evaluate the efficacy of new drugs. The PASI combines assessments of the percentage of body area affected, erythema, desquamation, and induration to produce a score ranging from 0 (no psoriasis) to 72 (the most severe case of psoriasis).

Methotrexate

Methotrexate, a synthetic analogue of folic acid, is the most widely used systemic agent in the treatment of psoriasis and psoriatic arthritis. It is probably effective because of its anti-inflammatory effects. It is also used to treat various malignancies because it has antimetabolite activity.

Methotrexate has the following actions:

Prescription is restricted to specialists or requires their approval. Methotrexate is administered either as a single weekly dose, usually orally, or as an intermittent oral schedule of three divided doses up to about 25mg over a 36-hour period once a week. Folic acid 1-5mg daily may help reduce adverse effects such as nausea and macrocytic anemia. Safety should be monitored by regular blood count, renal and liver function tests. Some patients require liver biopsy.

Adverse reactions include:

Acitretin

Acitretin is an oral retinoid (vitamin A derivative) used to treat psoriasis and other disorders of keratinisation. It appears to thin down thick psoriatic plaques and reduce inflammation. Acitretin is especially useful for pustular psoriasis, erythrodermic psoriasis and palmoplantar keratoderma.

The usual dose is 10-50mg daily, which must be prescribed by a dermatologist. It can be combined with other topical or systemic therapy and is especially useful with phototherapy. Monitoring requires pregnancy testing in females, complete blood count, lipids and liver function tests.

Adverse effects often limit tolerability and include:

Ciclosporin

Ciclosporin is an effective immunosuppressive agent used to prevent allograft rejection. It is very effective in the treatment of all forms of psoriasis.

Ciclosporin is a calcinerin inhibitor, which inhibits T cell activation and so reduces the production of cytokines especially IL-2 and interferon-γ.

In New Zealand, it is funded for severe psoriasis on Special Authority application using doses of 2.5 to 5mg/kg/day. Renal function and blood pressure must be carefully monitored and may require dose reductions or treatment interruptions.

Adverse effects include:

Other immunosuppressive agents

Although less effective that methotrexate and ciclosporin, the following immunosuppressive medications are sometimes used to treat psoriasis:

Biologics

Infliximab

Infliximab is an anti-TNFα humanized monoclonal antibody. It is quickly very effective in controlling psoriasis (up to 80% achieve 75% reduction in PASI) and may result in prolonged remissions. It is delivered IV three times over six weeks. Concurrent treatment with methotrexate is recommended to prevent formation of anti-infliximab antibodies. Untreated tuberculosis must be eliminated prior to treatment.

Etanercept

Etanercept is a fusion protein, which acts as a competitive inhibitor of TNF-α. Thirty percent of those treated twice weekly with subcutneous etanercept achieve 75% reduction in PASI. It may be associated with activation of tuberculosis but otherwise appears to have an excellent safety profile.

Adalimumab

Adalimumab is a recombinant monoclonal antibody directed against TNF. It is delivered by subcutaneous injection every 2 weeks. About 70% of patients achieve a 75% reduction in PASI at 16 weeks.

Ustekinumab

Ustekinumab is a human monoclonal antibody that antagonises interleukin 12 (IL-12) and IL-23. It is delivered by subcutaneous injection every 12 weeks. It is slightly more effective than TNF-alpha inhibitors.