Systemic therapy

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