INTRODUCTION
Psoriasis is a chronic, inflammatory/immune disorder mediated
by a host of genetic and environmental risk factors.
According to the National Institutes of Health, the disorder afflicts between 5.8 and 7.5 million people in the United
States.1 Patients with psoriasis are also at risk for developing psoriatic arthritis, a sero-negative inflammatory arthropathy that develops in 5% to 30% of patients with cutaneous disease.2
Psoriasis disrupts many aspects of life, including sleep, sexual activities, walking, and use of hands.3 Nearly 60% of patients with psoriatic skin and 40% with psoriatic arthritis report that the disorder is a large problem in their everyday life,4 with the quality of life impairment mirroring chronic illnesses like cancer,
heart disease and diabetes.5 It is estimated that 56 million hours of work are lost each year nationwide by people with psoriasis,6 bringing the total cost of the disorder in the U.S. to $1500 per patient per year or approximately $11.25 billion annually
for the treatment of psoriasis in the US.7
Over the last decade, new biologic agents that target tumor necrosis
factor and T-lymphocyte mechanisms have been added to the otherwise limited armamentarium of therapies for psoriasis that traditionally have included ultraviolet light, methotrexate, cyclosporine, and acitretin. Although these biologic drugs have demonstrated efficacy, tolerability, and short-and long-term safety, many patients either do not respond to these agents or have experienced adverse events. With improved understanding
of the relatively new Th17 immunologic pathway, a new targeted biologic therapy known as ustekinumab has emerged and shows excellent promise as an addition to our array of psoriasis
treatments.
Immunology of Psoriasis: IL-12 and IL-23
IL-12 and IL-23 are both heterodimers, the former comprised of a p40 and p35 subunit, the latter comprised of a p40 subunit
identical to the IL-12p40 subunit and a unique p19 subunit. Both cytokines are produced by antigen-presenting cells such as Langerhans cells, keratinocytes, and T-cells and function as activators of other T-cells and natural killer cells. IL-12 stimulates
naïve CD4+ cells to commit to the Th1 pathway, a pathway known to mediate autoimmunity and to regulate cell-mediated immunity against intracellular pathogens.8 IL-23 is necessary for the initiation and maintenance of a recently discovered
