Clobetasol Versus Pimecrolimus for Vulvar Lichen Sclerosus

Lichen sclerosus (LS) is a chronic cutaneous disorder affecting approximately one in seventy
women. Presenting symptoms may include intense pruritis, pain, burning, and severe
dyspareunia. The typical lesions of LS are white plaques and papules, often with areas of
echymosis, excoriation, and ulceration. Often, LS causes destruction of the vulva
architecture. In addition, 4-6% percent of women with LS will develop vulvar carcinoma. The
histopathologic changes of LS are distinctive and make biopsy a very useful diagnostic tool.
While there is no known cure for LS, the current gold standard treatment is ultra-potent
corticosteroids. When properly administered, topical ultra-potent corticosteroids help to
resolve the symptoms of pruritis and burning and can prevent further vulvar scarring. In
addition, proper treatment reverses the underlying histopathologic changes of LS, and
preliminary data shows that the risk of malignant transformation also declines. Although
treatment with topical corticosteroids is effective, topical corticosteroids have serious
local and systemic side effects, including dermal thinning, skin atrophy, superimposed
fungal infections, rebound dermatitis, and adrenal insufficiency.

Pimecrolimus cream 1% (Elidel®, Novartis Pharmaceutical) is a topical calcineurin inhibitor
that binds to macrophilin-12 and inhibits cytokine synthesis by T lymphocytes. Elidel has
been approved by the FDA for the treatment of mild to moderate atopic dermatitis. In theory,
as Elidel inhibits T lymphocytes, it should effectively treat lichen sclerosus. In addition,
as Elidel does not inhibit keratinocytes, or affect collagen synthesis, it does not cause
dermal atrophy. Therefore, Elidel may be an effective and safer alternative treatment for
LS. This study is designed to compare the effectiveness and safety of Elidel 1% cream versus
an ultra-potent corticosteroid (clobetasol 0.05% cream) for the treatment for vulvar LS.

Inclusion Criteria:

- Female, 18 years or older.

- With a diagnosis of biopsy proven active vulvar lichen sclerosus.

- Signed written informed consent.

- Willingness and ability to comply with the study requirements.

- Negative urine pregnancy tests must be documented for all females of childbearing
potential prior to enrollment.

- Two forms of birth control will be required for women with childbearing potential.

- IGA at baseline ≥1

- Subjects must have ≥ 4 or greater (on a 0 to 10 point scale) on at least one of the
two visual analog scales (pruritus or pain/burning).

Exclusion Criteria:

- Who have received systemic immunosuppressants (e.g. corticosteroids) within 4 weeks
prior to participation in the study.

- Who have been treated with topical therapy (e.g., topical corticosteroids,
pimecrolimus, and tacrolimus) at the affected area within two weeks prior to
participation in the study.

- Who are immunocompromised (e.g., lymphoma, AIDS, Wiskott-Aldrich Syndrome) or have an
uncontrolled malignant disease.

- Who have a history of lymphoma

- Who have lympadenopathy

- Who have active vulvar herpes, molluscum, or condyloma

- Who suffer from systemic or generalized infections (bacterial, viral or fungal).

- Who have been diagnosed with lichen planus, psoriasis, candidiasis, intraepithelial
neoplasia, or carcinoma of the vulva.

- Who have been diagnosed with diabetes mellitus or Netherton’s syndrome.

- Menstruating females of childbearing potential who are not using two medically
accepted methods of contraception during the study. Medically approved contraception
may, at the discretion of the investigator, include abstinence.

- Women who are breastfeeding.

- Who had received an investigational drug within four weeks prior to the study or who
intend to use other investigational drugs during the course of this study.

- Who are hypersensitive to pimecrolimus or clobetasol or any of the components of the
creams.

- Patients with severe medical condition(s) that in the view of the investigator
prohibits participation in the study.

- Who have a history of substance abuse or any factor, which limits the subject’s
ability to cooperate with the study procedures.

- Who are uncooperative, known to miss appointments (according to subjects’ records)
and are unlikely to follow medical instructions or are not willing to attend
regularly scheduled visits.