OR WAIT 15 SECS
In this table, we highlight how psoriasis treatments have evolved over the past four decades.
Methotrexate was approved for the treatment of psoriasis in the 1970’s, but its widespread adop- tion for the treatment of severe psoriasis was slow to gain traction.
Psoriasis was considered a disorder of keratiniza- tion. Patients with moderate-to-severe disease were treated with with topical steroids, tar preparations, sun- light and various forms of ultraviolet light-UVB boxes and photochemotherapy, or PUVA. Scientists would dis- cover during the decades to follow that the disease and treatment were far more complicated.
Kreuger JG abd Gottlieb AB at Rockefeller University in New York,â¨ NY, demonstrated in a paper published in 1990 that psoriasis was likely driven by inflammation, specifically T-cells. The rec- ognition of Krueger’s and Gottlieb’s find-â¨ings spurred more widespread use of methotrexate, as well as the investigation of cyclosporine as a systemic therapy, leading to the FDA’s approval of cyclosporine for psoriasis treatment in 1997.
Alefacept (Amevive, Biogen Idec) and efalizumab (Raptiva, Genentech), therapies that affected T-cell activation and T-cell migration, came onto the scene in the early 2000s but fell by the wayside, making room for the tumor necrosis factor (TNF) inhibitors-the next big wave in psoriasis therapy
TNF inhibitors entered dermatology via impressive outcomes in rheumatology, according to Dr. Martin. The options include etaner- cept (Enbrel, Amgen, approved for psoriasis in 2004), infliximab (Remicade, Janssen, 2006) and adalimumab (Humira, Abbvie, 2008). Researchers began to uncover that psoriasis is an inflam- matory disorder. And that it’s not confined to the skin; rather, it’s a systemic disorder, with 20% to 30% of patients developing psoriatic arthritis. And patients with psoriasis are at higher risk for numerous other comorbidities, including cardiovascular events, met- abolic syndrome and kidney disease. Anti-TNF therapy paved the way for discovering the roles of other treatment targets, including the roles of interleukin (IL-) 23 and IL-17
The recogniztion of IL 17 as a major inflammatory driver in the skin led to the development of the IL-17 inhibitor family. Additionally, the recognition of the importance of IL-23, which is often referred to as the ‘master cytokine,’ in the pathogenesis of psoriasis, led to targeted therapy initially with ustekinumab (Stelara, Jans- sen, 2009), an IL 12/23 blocker FDA approved a breakthrough small molecule therapy apremilast (Otezla, Celgene), phosphodiesterase 4 (PDE4) inhibitor, for psoriasis and psoriatic arthritis
The psoriasis drug pipeline is focused on small mol- ecules, particularly the Janus kinase (JAK) inhibitors. While tofacitinib (Xeljanz, Pfizer), approved for pso- riatic arthritis, did not clear the FDA for psoriasis due to safety concerns, studies showed the 10mg, twice daily dose had similar efficacy to etanercept. Recently phase 2 data for tyrosine kinase 2, or TYK2 inhibitors, has demonstrated remarkable efficacy