Novel investigational vascular endothelial growth factor (VEGF) receptor antagonists for psoriasis

ABSTRACT

Introduction: Affecting 1 million people in the UK, psoriasis is a commonly diagnosed inflammatory disease arising from autoimmune processes that are triggered by environmental factors in genetically susceptible individuals. The pathophysiology of psoriasis has been widely studied and there is evidence that angiogenesis is a key component.

Areas covered: In this review the role of vascular endothelial growth factor-A (VEGF), as a key angiogenic mediator in psoriasis pathogenesis is discussed. VEGF is found in higher levels in plaques, normal skin and plasma of patients with psoriasis. The level of VEGF also fluctuates in accordance with disease activity and in response to conventional treatments. There are several VEGF inhibitors currently licenced for use; primarily in the fields of oncology and there are case reports of patients being treated with these therapies for metastatic cancer who have demonstrated significant improvement in their psoriasis. VEGF inhibitory agents have suggested promising utility for the treatment of psoriasis following animal studies.

Expert opinion: VEGF may represent a novel treatment target in psoriasis. However, VEGF inhibitors can cause significant side effects such as hypertension and left ventricular dysfunction. The risks of treatment must be carefully evaluated before VEGF inhibitors are trialled or advocated for psoriasis.

KEYWORDS:

• Psoriasis
• treatment
• angiogenesis
• vascular endothelial growth factor
• VEGF

Article highlights

• VEGF-mediated angiogenesis contributes to pathophysiology of psoriasis.

• The amount of VEGF in the plasma and skin fluctuates in line with clinical disease severity and in response to treatment.

• TNF-α upregulates VEGF expression. Experimental agents IBI303 and HK have demonstrated the anti-angiogenic effects of TNF-α inhibition.

• Case reports detailing clinical improvement of psoriasis in patients treated with anti-VEGF drugs for cancer have been published.

• Murine studies have demonstrated the efficacy of anti-VEGF agents in the treatment of psoriasiform skin lesions.

  • MF-1 and DC101 – monoclonal antibodies to VEGFR-1 and VEGFR-2

  • Valpha – a chimeric decoy receptor that targets VEGF and TNF-α

  • NVP-BAW2881 – a receptor TK that can be administered orally or topically

  • G6-31 – a monoclonal antibody with high binding affinity for mouse and human VEGF

• Despite the evidence base supporting the utility of anti-VEGF therapy for the treatment of psoriasis, further research is required and safety concerns must be addressed before use in dermatological practice.This box summarizes key points contained in the article.

Declaration of interest

Helen young has received grant support from Biogen Idec, Galderma, LEO Pharma, Novaris, Schering-plough, Stiefel and Wyeth/Pfizer. She has acted a s consultant for Teva Pharmaceuticals and on advisory boards for Abbott/Abbvie, Amgen, Eli Lilly, Janssen-Cilag and LEO pHarma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.