Vascular endothelial growth factor inhibitors: investigational therapies for the treatment of psoriasis

Figures & data

Table 1 Licensed vascular endothelial growth factor inhibitors reported to affect coexisting psoriasis during treatment of malignancy

Year	Reference	Author	Drug	Mechanism of action	Indication for treatment	Preceding duration of psoriasis (years)	Effect of treatment on coexisting psoriasis	Duration of effect
2007	22	Keshtgapour et al	Sunitinib (SU-011248)	Receptor tyrosine kinase inhibitor	Metastatic renal cell carcinoma	20	“Virtual clearance”	Throughout treatment with cyclical exacerbations
2009	21	Akman et al	Bevacizumab	Anti-VEGF monoclonal antibody	Metastatic colon carcinoma	40	Reduction in PASI from 16.8 to 1.4	At least 3 months (duration of follow-up)
2010	23	Fournier et al	Sorafenib	Multikinase inhibitor	Metastatic renal clear cell carcinoma	56	Clearance of longstanding plaques	4 months until change of treatment
2010	24	Narayanan et al	Sunitinib	Receptor tyrosine kinase inhibitor	Metastatic renal cell carcinoma	5	“Significant improvement”	3.5 years; ongoing therapy with cyclical exacerbations

Note: Copyright © 2011, Informa. Adapted with permission from Crawshaw AA, Griffiths CEM, Young HS. Investigational VEGF antagonists for psoriasis. Expert Opin Invest Drugs. 2012; 21:33–43.¹¹⁴

Abbreviations: PASI, psoriasis area and severity index; VEGF, vascular endothelial growth factor.

Table 2 Preclinical murine studies investigating possible vascular endothelial growth factor inhibitors

Refereence	Author	Agent	Mechanism of action	Method of administration	Principal findings in treated mice
25	Xia et al (2003)	VEGF-Trap	Fusion protein (decoy receptor)	Subcutaneous injection	Improved clinical appearance, normalization of histological features including ↓ parakeratosis, ↓ vascularity and ↓ epidermal markers (eg, K6)
110	Kunstfeld et al (2004)	MF-I and DC 101	Rat anti-VEGFR-1 mAb and anti VEGFR-2 mAb	Intra-peritoneal injection	↓ skin inflammation, ↓ edema, and ↓ lymphatic vessel enlargement
74	Haiin et al (2008)	NVP-BAW2881	Receptor tyrosine kinase inhibitor	Oral or topical	Both formulations effective oral > topical, improved clinical appearance, ↓ number and size of blood vessels, normalization of histological features including ↓ leucocyte infiltration
109	Schonthaler et al (2009)	G6-3I	Anti-VEGF mAb	Subcutaneous injection	Improved clinical appearance, normalization of histological features including ↓ epidermal thickness, ↓ vascularity, and ↓ leucocyte infiltration
112	Jung etal (201 1)	Valpha	Chimeric fusion protein (anti-TNF and anti-VEGF decoy receptor)	Subcutaneous injection	↓ epidermal hyperplasia, ↓ blood vessel area, and ↓ lymphatic vessel area

Note: ↓ represents a decrease. Copyright © 201 I, Informa. Adapted with permission from Crawshaw AA, Griffiths CEM, Young HS. Investigational VEGF antagonists for psoriasis. Expert Opin Invest Drugs. 2012; 2 1:33–43.¹¹⁴

Abbreviations: mAb, monoclonal antibody; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor.

CrawshawAAGriffithsCEMYoungHSInvestigational VEGF antagonists for psoriasisExpert Opin Invest Drugs2012213343

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