Antivascular endothelial growth factor-A therapy: a novel personalized treatment approach for psoriasis

Chronic plaque psoriasis is an inflammatory skin disease in which genetic predisposition along with environmental factors lead to the development of the disease, which affects 2% of the UK's population and is associated with extracutaneous morbidities and a reduced quality of life. A complex crosstalk between innate and adaptive immunity, the epithelia and the vasculature maintain the inflammatory milieu in psoriasis. Despite the development of promising treatment strategies, mostly targeting the immune system, treatments fail to fulfil every patient's goals. Vascular endothelial growth factor-A (VEGF-A) mediates angiogenesis and is upregulated in the plaques and plasma of patients with psoriasis. Transgenic expression of VEGF-A in experimental models led to the development of skin lesions that share many psoriasis features. Targeting VEGF-A in in vivo models of psoriasis-like inflammation resulted in disease clearance. Anti-angiogenesis treatments are widely used for cancer and eye disease and there are clinical reports of patients treated with VEGF-A inhibitors who have experienced Psoriasis Area and Severity Index improvement. Existing psoriasis treatments downregulate VEGF-A and angiogenesis as part of their therapeutic effect. Pharmacogenetics studies suggest the existence of different genetic signatures within patients with psoriasis that correspond with different treatment responsiveness and disease severity. There is a subset of patients with psoriasis with an increased predisposition to produce high levels of VEGF-A, who may be most likely to benefit from anti-VEGF-A therapy, offering an opportunity to personalize treatment in psoriasis. Anti-VEGF-A therapies may offer an alternative to existing anticytokine strategies or be complementary to standard treatments for the management of psoriasis.