Psoriasis is a chronic inflammatory skin disorder. The prevalence of psoriasis is estimated at approximately 100 million people worldwide. In mild-to-moderate, as well as moderate-to-severe, psoriasis, 70–80% of patients start with topical agents and continue to use them with other active therapies. This group of patients can benefit from topical treatment with minimal systemic exposure. The expression levels of IL-23 and IL-17 are upregulated in psoriatic skin compared with non-lesional skin, associated with psoriasis pathogenesis. The skin epidermal proliferation and psoriasis are caused by overactive Th17 cells, which are promoted and stabilized by the activated IL-23 receptor, forming part of the positive feedback loop. FDA approved biologics in IL-23/IL-17 axis (ustekinumab, guselkumab, risankizumab, tildrakizumab, ixekizumab, secukinumab and brodalumab) demonstrated superior clinical efficacy in the systemic treatment of moderate-to-severe psoriasis, providing the clinical proof of concept of the IL-23/IL-17 axis as a major immune pathway underlying the pathophysiology of psoriasis. However, due to the large size and poor permeability into skin, biologics are not suitable to deliver via topical route. Current topical treatments of mild-to-moderate psoriasis are corticosteroids and vitamin D analogues, which have limited efficacy with significant side effects so that patients must avoid long-term use. This chapter reviews current molecular targeted therapeutics under development for topical treatment of psoriasis.
Part of the book: Psoriasis