Pilot Study of Ustekinumab for Subjects With Chronic Atopic Dermatitis
Status:
Completed
Trial end date:
2015-03-01
Target enrollment:
Participant gender:
Summary
Atopic dermatitis (AD) is a chronic disease associated with intense itching, which affects
most aspects of everyday life in the majority of patients. Acute inflammation and
extensor/facial involvement is common in infants, whereas chronic inflammation increases in
prevalence with age, as do localization to flexures. AD has a complex background
characterized by immune activation, increased epidermal thickness in chronic diseased skin,
and defective barrier function. In normal, healthy skin, the outer layer of the epidermis,
the stratum corneum is made up flattened dead cells called corneocytes held together by a
mixture of lipids and proteins. The stratum corneum and, in particular, the lipid layer are
vital in providing a natural barrier function that locks water inside the skin and keeps
allergens and irritants out. In people with AD, the barrier function is defective, which
leads to dry skin. As the skin dries out, it cracks allowing allergens and irritants to
penetrate.
Mild AD can be controlled with emollients and topical medications. However, moderate to
severe AD is extremely difficult to control and requires systemic treatment that is often
unsatisfactory due to impracticality and lack of effectiveness. Only three therapeutic
options exist for moderate to severe AD, including: 1) oral steroids 2) cyclosporine A (CsA),
that is not widely used in the US as it is not FDA approved for AD and 3) ultraviolet
phototherapy. Oral steroids and CsA treatments have major side effects and UV radiation
therapy is highly inconvenient for patients. Several biologic medications, such as TNF-alpha
inhibitors, are effective, convenient, and relatively safe therapies for psoriasis, but have
thus far not shown efficacy in AD. Ustekinumab is a unique biologic medication that may
specifically target AD.
The investigators study will determine whether there is a reversal of the skin thickness and
the immune pathways involved in the disease during treatment with Ustekinumab and what
specific immune cells are involved. The investigators are also interested to understand how
the clinical reversal of the disease will correlate with tissue reversal of the disease.