Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis

Abstract Objective To systematically review and provide information on the incidence of psoriasis and quantify global, regional, and country specific estimates of its prevalence. Design Systematic review and meta-analysis. Data sources Medline, Embase, Web of Science, SciELO, Korean Journal Databases, Russian Science Citation Index, WPRIM, SaudiMedLit, Informit, IndMed, and HERDIN were searched systematically from their inception dates to October 2019. Methods Studies were included if they reported on the incidence or prevalence of psoriasis in the general population. Incidence data were summarised descriptively, whereas bayesian hierarchical models were fitted to estimate the global, regional, and country specific prevalence of psoriasis. Results 41 164 records were identified and 168 studies met the inclusion criteria. In adults, the incidence of psoriasis varied from 30.3 per 100 000 person years (95% confidence interval 26.6 to 34.1) in Taiwan to 321.0 per 100 000 person years in Italy. The prevalence of psoriasis varied from 0.14% (95% uncertainty interval 0.05% to 0.40%) in east Asia to 1.99% (0.64% to 6.60%) in Australasia. The prevalence of psoriasis was also high in western Europe (1.92%, 1.07% to 3.46%), central Europe (1.83%, 0.62% to 5.32%), North America (1.50%, 0.63% to 3.60%), and high income southern Latin America (1.10%, 0.36% to 2.96%). Conclusions Eighty one per cent of the countries of the world lack information on the epidemiology of psoriasis. The disease occurs more frequently in adults than in children. Psoriasis is unequally distributed across geographical regions; it is more frequent in high income countries and in regions with older populations. The estimates provided can help guide countries and the international community when making public health decisions on the appropriate management of psoriasis and assessing its natural history over time. Systematic review registration PROSPERO CRD42019160817.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

Tapinarof (GSK2894512) is a naturally derived topical treatment with demonstrated efficacy for patients with psoriasis and atopic dermatitis, although the biologic target and mechanism of action had been unknown. We demonstrate that the anti-inflammatory properties of tapinarof are mediated through activation of the aryl hydrocarbon receptor (AhR). We show that tapinarof binds and activates AhR in multiple cell types, including cells of the target tissue-human skin. In addition, tapinarof moderates proinflammatory cytokine expression in stimulated peripheral blood CD4+ T cells and ex vivo human skin, and impacts barrier gene expression in primary human keratinocytes; both of these processes are likely to be downstream of AhR activation based on current evidence. That the anti-inflammatory properties of tapinarof derive from AhR agonism is conclusively demonstrated using the mouse model of imiquimod-induced psoriasiform skin lesions. Topical treatment of AhR-sufficient mice with tapinarof leads to compound-driven reductions in erythema, epidermal thickening, and tissue cytokine levels. In contrast, tapinarof has no impact on imiquimod-induced skin inflammation in AhR-deficient mice. In summary, these studies identify tapinarof as an AhR agonist and confirm that its efficacy is dependent on AhR.