Systemic therapy in atopic dermatitis

A variety of systemic treatments have been used for the treatment of severe atopic dermatitis, many of which are off label. Below we discuss the treatments licensed for this indication.

Oral glucocorticoids

Many European countries continue to use oral glucocorticoids for the management of atopic dermatitis (Wollenberg et al., 2018). They should only be used short-term, preferably in combination with topical corticosteroids, to manage acute flares of severe, widespread disease. Given the risk of adverse effects, oral glucocorticoids should be tapered and replaced with an alternative immunosuppressant (Thomsen, 2014). The use of systemic steroids in children should be undertaken with even greater caution than that with adults (Wollenberg et al., 2018).

The mechanism of action for oral glucocorticoids is consistent with that for topical corticosteroids, but experienced at a broader, systemic level.

Ciclosporin A

Ciclosporin A is an oral calcineurin inhibitor that promotes immunosuppression. In many European countries, it is a first-line treatment for adult patients with chronic severe atopic dermatitis who require systemic treatment. While effective, treatment should not exceed two years and patients should be monitored for severe adverse effects. Common adverse effects include nephrotoxicity and hypertension with renal effects more likely if the daily dose exceeds 5 mg/kg, serum creatinine levels are elevated, or the patient is elderly (Wollenberg et al., 2018).

Ciclosporin A has a similar mechanism of action to the topical calcineurin inhibitors except it interacts with cyclophilin rather than macrophilin-12 (Gutfreund et al., 2013).

Anti-IL-4/IL-13

The receptors for IL-4 and IL-13 share a common α-chain. A recently approved monoclonal antibody, dupilumab, targets this α-chain and blocks the action of IL-4 and IL-13. In 2017, dupilumab was approved in Europe and the USA for the management of moderate-to-severe adult atopic dermatitis. A series of randomised controlled trials have confirmed the efficacy of dupilumab with a recent study confirming continued activity over 1 year of continued treatment (Thaci et al., 2016; Simpson et al., 2016; Blauvelt et al., 2017). From the available data, approximately one-third of treated patients become clear or almost clear of the atopic dermatitis based on the Investigator Global Assessment (IGA) and up to 70% of patients achieve an Eczema Area and Severity Index (EASI) 75 or higher improvement in their skin. Dupilumab also has an impressive safety profile with conjunctivitis the only adverse event observed more frequently than placebo (Wollenberg et al., 2018).

Mechanism of action

Interleukin-4 and IL-13 are critical components of the Th2-driven immune response observed in atopic dermatitis (Wong et al., 2017) and promote IgE production by B cells, dendritic cell differentiation, activation of T cells and recruitment of eosinophils (Peng & Novak, 2015). 

Dupilumab inhibition of IL-4 and IL-13 signalling.

Figure 21: Dupilumab inhibition of IL-4 and IL-13 signalling. Adapted from Barranco et al., 2017.
IL, interleukin; JAK, Janus kinase; STAT, signal transducer and activator of transcription; Tyk, tyrosine kinase.