INTRODUCTION
Psoriasis is a chronic and complex genetic immune-mediated
disease affecting up to 2% of the US population.1 The
pathogenesis of psoriasis stems from dysregulated inflammation,
which leads to hyperproliferation of the basal keratinocytes
and incomplete differentiation of the epidermis. The disease
process is perpetuated by infiltration of helper T cells 1 (Th1) and
helper T cells 17 (Th17), dermal dendritic cells, Langerhans cells,
and neutrophils with altered levels of chemokines and integrins.1,2
Biologic agents are widely used treatments for moderate to
severe chronic plaque psoriasis and they target specific components
of the immunologic pathway. While tumor necrosis
factor-α (TNF-α) inhibitors have been available for treatment
in psoriasis for more than 10 years, ustekinumab is the only
monoclonal antibody specifically targeting interleukin-12 (IL-12)
and interleukin-23 (IL-23) that is currently approved by the US
Food and Drug Administration (FDA).2,3
Both IL-12 and IL-23 are involved in the differentiation of naïve
T cells into Th cells. Th1 cells develop from naïve T cells after
exposure to IL-12, whereas IL-23 stimulates proliferation of Th17
cells. These Th cells each express unique cytokines, some of
which are proinflammatory cytokines that are further involved
in the immune response and subsequent systemic inflammation.
Both IL-12 and IL-23 share a common p40 subunit, which is
overexpressed in psoriatic plaques.4
Ustekinumab is a human IgG1κ monoclonal antibody that binds
with high affinity and specificity to the p40 protein subunit shared by both the IL-12 and IL-23 cytokines.5 Three phase 3 clinical trials
have shown that ustekinumab produces a rapid improvement in
the majority of patients with moderate to severe plaque psoriasis.
6,7,8 The European Medicines Agency (EMA) approved the use
of ustekinumab for moderate to severe plaque psoriasis in January
2009, and the FDA in September 2009.4 In September 2013
they both approved ustekinumab for the treatment of moderateto-
severe psoriatic arthritis in adult patients.
Five-year safety data have recently been published on patients
exposed to ustekinumab.4,5,9 These data were pooled
from 4 studies of ustekinumab for psoriasis with analysis of
3,117 patients who received at least 1 dose of ustekinumab,
with 1,482 patients treated for 4 or more years and 838 patients
treated for 5 or more years. Rates of adverse events
(AEs), serious AEs, infections, nonmelanoma skin cancers,
other malignancies, and major cardiac AEs were analyzed by
dose and year of exposure. Rates of overall mortality and
other malignancies were comparable with those expected
in the general US population, and no dose-related or cumulative
toxicity was observed with continued exposure to
ustekinumab for up to 5 years.4,5,9 Rates of AEs reported in
ustekinumab psoriasis trials are generally comparable with
those reported for other biologics approved for the treatment
of moderate-to-severe psoriasis.10
Since its approval in September 2009, our psoriasis specialty clinic
has prescribed ustekinumab for psoriasis treatment to over 450
patients. We conducted a retrospective analysis of patients treated
