Skin disease

Therapeutics for the management of psoriasis include both pharmacological (topical corticosteroids and non-corticosteroids, emollients, systemic therapies, biologic therapy) and non-pharmacological interventions (e.g. phototherapy).

Topical therapy is offered as first-line treatment. Second-line treatment (phototherapy) or third-line treatment (systemic therapy) options may be offered at the same time when topical therapy alone is unlikely to adequately control psoriasis (e.g. in cases of extensive disease, when disease has progressed to 'moderate' level or where topical therapy is likely to be ineffective (e.g. for nail disease)).

Topical treatment for chronic stable plaque psoriasis on extensor surfaces of the trunk and limbs involves the use of vitamin D analogues, coal tar, dithranol, and the retinoid tazarotene, but these are not suitable for more inflammatory forms of psoriasis. Localised acute or subacute inflammatory psoriasis should be treated topically with emollients or with a moderate potency corticosteroid.

Due to the skin-thinning effect of corticosteroids, facial, flexural and genital psoriasis should be managed with short-term use of a mild or moderate potency topical corticosteroid. If this proves inadequate calcitriol (1,25-dihydroxyvitamin D3) or tacalcitol can be used for longer-term treatment. Topically applied pimecrolimus or tacrolimus [unlicensed indication] can be used short-term, under specialist supervision, in patients whose disease is unresponsive or who are intolerant of this treatment regimen.

Topical corticosteroids: topical corticosteroids such as desoximetasone are not generally suitable for long-term use, or as single agents.

Vitamin D analogues:  tazarotene, calcipotriol, tacalcitol and calcitriol (the latter two are the least likely to cause irritation). These drugs are the first-line choice for the long-term treatment of plaque psoriasis. Use should be avoided in patients with calcium metabolism disorders.

Systemic therapy (non-biologic) includes use of potent corticosteroids, often in conjunction with vitamin D, a vitamin D analogue or acitretin (which is a  metabolite of etretinate, a vitamin A derivative). This level of therapy must be delivered  in specialist settings only and requires close monitoring and supervision. Topical use of potent corticosteroids on widespread psoriasis can also lead to systemic as well as local side-effects. Acretin's therapeutic effect should be evident after 2 to 4 weeks and maximum benefit should be achieved after 4 months. Use for >6 months is not recommended, but longer treatment with the lowest effective dose may provide benefit to some patients. Acitretin confers a risk of teratogenicity for up to 3 years after stopping use, therefore women of child-bearing age must initiate an effective method of contraception before, during and for 3 years after taking acitretin. Despite this, acitretin is considered the least toxic systemic treatment for psoriasis.

Systemic therapy (biologic) is reserved for cases of severe and very severe psoriasis. These types of agents are generally monoclonal antibodies or IgG-fusion proteins that target key drivers of psoriasis pathology such as TNFα and pro-inflammatory cytokines. All of these therapeutics are administered in a clinical setting under strict supervision.

TNFα neutralising agents:

• Adalimumab*, golimumab and certolizumab pegol are monoclonal antibodies that bind to and functionally neutralise circulating TNFα to mediate an anti-inflammatory effect.
• Etanercept* is a fusion protein containing petide sequences of TNF receptor 2 and IgG1-Fc. Like the anti-TNFα antibodies, it neutralises circulating TNFα.

Cytokine inhibitors:

IL-23 and IL-17 are key drivers of inflammation in autoimmune diseases like psoriasis, and as such have been targeted by the pharmaceutical industry for the development of novel disease-modifying therapies.

• Guselkumab and tildrakizumab are both anti-IL-23p19 monoclonal antibodies that bind the p19 subunit of the IL-23 heterodimer, and functionally inhibit formation of active IL-23 and signalling via the IL-23 receptor pathway.
• Ustekinumab has a different molecular target, but effects a similar mechanistic outcome. It targets IL-12B which is the common p40 subunit of the active IL-12 and IL-23 hetereodimers. So like guselkumab and tildrakizumab, this monoclonal antibody targets the aberrant IL-23 pathway that is known to drive psoriasis pathology.
• Brodalumab, ixekizumab and secukinumab are anti-IL-17A monoclonal antibodies, that block pro-inflammatory signalling.

* Biosimilar versions of these originator agents have been approved for clinical use.