INTRODUCTION
Psoriasis is a chronic, inflammatory, remitting/relapsing autoimmune dermatological condition characterized by scaly, erythematous plaques. Patients with psoriasis experience a significantly reduced quality of life due to discomfort from the physical symptoms as well as disability and disfigurement. They also have a higher risk of comorbid conditions, including psoriatic arthritis (PsA), cardiovascular disease, inflammatory bowel disease, metabolic syndrome, chronic kidney disease, mood disorders, including depression, and malignancy.1
While the etiology of psoriasis is unknown, there have been many recent advances in the understanding of its pathogenesis. We now know that psoriasis is a T-cell mediated disease involving a dysregulated inflammatory response of the interleukin (IL) 23/T-helper (Th)-17 pathway. In this process, IL- 23 is overproduced by dendritic cells and keratinocytes, which stimulates Th17 cells within the dermis to produce and release additional inflammatory cytokines. This, in turn, activates an inflammatory cascade of downstream effector molecules including IL-17A, IL-17F, IL-22, IL-21, and tumor necrosis factor-α (TNF-α), which is responsible for the keratinocyte hyperproliferation that results in the characteristic scaly plaques.2-4 Studies conducted in mice demonstrate that removing either IL-23 or IL-17 decreases the progression of psoriasis.5,6 Mice injected with monoclonal antibodies targeting IL-17 blocked, or neutralized, downstream signaling of this cytokine and decreased epidermal hyperplasia.5
Similarly, genetically modifying mice to not express IL- 23 or IL-17 receptors significantly reduced psoriatic lesion development upon stimulation with the lesion-causing tumor promoter 12-O-tetradecanoylphorbol-13-acetate.7 This greater understanding of the immune-mediated pathology of the disease has led to the development of monoclonal antibodies and fusion proteins that block specific cytokines or cytokine receptors involved in psoriatic inflammation.
Currently available biologics are the TNF-α inhibitors infliximab, adalimumab, certolizumab, and etanercept; the IL-12/13 inhibitor ustekinumab; the IL-17 inhibitors secukinumab and ixekizumab; the IL-17 receptor blocker brodalumab; and the IL-23 inhibitors guselkumab, tildrakizumab, and risankizumabrzaa.1 Biosimilars to infliximab, adalimumab, and etanercept are also available.
While the etiology of psoriasis is unknown, there have been many recent advances in the understanding of its pathogenesis. We now know that psoriasis is a T-cell mediated disease involving a dysregulated inflammatory response of the interleukin (IL) 23/T-helper (Th)-17 pathway. In this process, IL- 23 is overproduced by dendritic cells and keratinocytes, which stimulates Th17 cells within the dermis to produce and release additional inflammatory cytokines. This, in turn, activates an inflammatory cascade of downstream effector molecules including IL-17A, IL-17F, IL-22, IL-21, and tumor necrosis factor-α (TNF-α), which is responsible for the keratinocyte hyperproliferation that results in the characteristic scaly plaques.2-4 Studies conducted in mice demonstrate that removing either IL-23 or IL-17 decreases the progression of psoriasis.5,6 Mice injected with monoclonal antibodies targeting IL-17 blocked, or neutralized, downstream signaling of this cytokine and decreased epidermal hyperplasia.5
Similarly, genetically modifying mice to not express IL- 23 or IL-17 receptors significantly reduced psoriatic lesion development upon stimulation with the lesion-causing tumor promoter 12-O-tetradecanoylphorbol-13-acetate.7 This greater understanding of the immune-mediated pathology of the disease has led to the development of monoclonal antibodies and fusion proteins that block specific cytokines or cytokine receptors involved in psoriatic inflammation.
Currently available biologics are the TNF-α inhibitors infliximab, adalimumab, certolizumab, and etanercept; the IL-12/13 inhibitor ustekinumab; the IL-17 inhibitors secukinumab and ixekizumab; the IL-17 receptor blocker brodalumab; and the IL-23 inhibitors guselkumab, tildrakizumab, and risankizumabrzaa.1 Biosimilars to infliximab, adalimumab, and etanercept are also available.
