systemic therapy

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Systemic agents should be given under the supervision of a dermatologist. They include:

methotrexate - given as a single dose each week (max. 0.5 mg/kg); complications include myelosuppression; hepatic fibrosis; and teratogenesis
- indicated for recalcitrant disease unresponsive to topical or phototherapy and is particularly useful if the patient has an associated arthropathy
- long-term use of methotrexate is associated with liver toxicity so regular liver function tests are required
  - incidence of cirrhosis is related to cumulative dose, and if this is below 1.5g the risk is low (1) - if this level has been reached then liver biopsy is required to check for signs of toxicity
    - if serial propeptide of type III procollagen levels remain normal repeat liver biopsies can be avoided (1)

retinoids
- useful agent for pustular and erythrodermic psoriasis but are less effective in chronic plaque psoriasis (1)
- if used as combination therapy with PUVA or UVB then this allows dose reduction and decreases the incidence of adverse effects

ciclosporin - 2.5 mg/kg/day; complications include hypertension; renal impairment; hypertrichosis; and increased risk of skin malignancy and lymphoma

Indications for systemic therapy (2) include:

failure of adequate trial of topical therapy
repeated hospital admissions for topical therapy
rxtensive chronic plaque psoriasis in the elderly or infirm
reneralised pustular or erythrodermic psoriasis
revere psoriatic arthropathy

Note that etretinate, methotrexate are specifically contraindicated for use in pregnancy.

NICE suggest (3):

Choice of drugs
- methotrexate should be offered as the first choice of systemic agent for people with psoriasis who require systemic therapy
- in people with both active psoriatic arthritis and any type of psoriasis that fulfils the criteria for systemic therapy consider the choice of systemic agent in consultation with a rheumatologist
- ciclosporin should be offered as the first choice of systemic agent for people who fulfil the criteria for systemic therapy and who:
  - need rapid or short-term disease control (for example a psoriasis flare) or
  - have palmoplantar pustulosis or
  - are considering conception (both men and women) and systemic therapy cannot be avoided
- consider changing from methotrexate to ciclosporin (or vice-versa) when response to the first-choice systemic treatment is inadequate
- acitretin should be considered for adults, and in exceptional cases only for children and young people, in the following circumstances:
  - if methotrexate and ciclosporin are not appropriate or have failed or
  - for people with pustular forms of psoriasis
Biological Therapy (third line therapy)
- indicated when the following criteria are both met:
  - disease is severe as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10
  - the psoriasis has not responded to standard systemic therapies including ciclosporin, methotrexate and PUVA (psoralen and long-wave ultraviolet radiation); or the person is intolerant of, or has a contraindication to, these treatments
- third-line therapy refers to systemic biological therapies such as the tumour necrosis factor antagonists adalimumab, etanercept and infliximab, and the monoclonal antibody ustekinumab that targets interleukin-12 (IL-12) and IL-23

Reference:

Prescriber (2005); 16 (8).
British Association of Dermatologists (2003). Psoriasis guideline.
NICE (September 2017). Psoriasis - the assessment and management of psoriasis

Last reviewed 01/2018

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