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Targeting IL-17 to treat psoriasis

Targeting IL-17 to treat psoriasis

Read time: 20 mins
This section of the Learning Zone describes the burden of disease for psoriasis and summarises the role of IL-17 in the development of psoriatic skin as well as the mechanism of action of the different anti-IL-17 biologics that are currently approved for treating moderate-to-severe psoriasis. Choose one of the subsections below, or scroll down the page, to learn more.

Why treat psoriasis?

Psoriasis is a common, lifelong, painful, disfiguring and disabling disease (World Health Organization, 2016).

The impact of psoriasis

Figure 1. The impact of psoriasis (Ortonne & Prinz, 2004; Menter et al., 2008; World Health Organisation, 2016; The International Federation of Psoriasis Associations, 2017).

Psoriasis has a substantial negative impact on individuals and patients with moderate-to-severe psoriasis often have poor physical and mental health-related quality of life (Menter et al., 2008). 

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Why target IL-17?

A large number of inflammatory cytokines are elevated in psoriasis lesional skin and the serum concentrations of a subset of these correlate with disease severity (Baliwag et al., 2015). 

An understanding of which cytokines play a pivotal role in the disease process has revealed potential therapeutic targets, and a number of cytokines have been successfully targeted, revolutionising treatment of this disease (Baliwag et al., 2015). 

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MoA of IL-17 treatments

A number of cytokines from the IL-17 family must bind to IL-17 receptor A (IL-17RA) in order to complete their biological function (Kyntheum® Summary of Product Characteristics, 2017).

Increased expression of IL-17A, IL-17C and IL-17F cytokines, which activate IL-17RA complexes on keratinocytes and immune cells, leads to inflammation and the clinical manifestations of psoriasis (Toy et al., 2006; Wright et al., 2008; Ramirez-Carrozzi et al., 2011; Martin et al., 2013).

 

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Treatments that block IL-17A signalling at the ligand level

Two anti-IL-17A treatments are currently available for the treatment of moderate-to-severe psoriasis.

Ixekizumab

Ixekizumab is a humanised IgG4 monoclonal anti body that binds interleukin 17A (both IL-17A and IL-17A/F) and is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy. 

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Treatments that block IL-17 signalling at the receptor level

Brodalumab

While other IL-17 biologics for moderate-to-severe psoriasis bind to the IL-17A ligand, the fully human IgG2 monoclonal antibody brodalumab binds to the IL-17 receptor subunit A, which blocks the inflammatory signalling not only of IL-17A but also IL-17F, IL-17A/F and IL-25 (Figure 6) (Campa et al., 2016; Kyntheum® Summary of Product Characteristics, 2017).

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References

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