The purpose of this study is to determine the safety and efficacy of Humira in the treatment
of pyoderma gangrenosum.
Pyoderma gangrenosum (PG) is an uncommon dermatosis that consists of nodules and pustules
that ulcerate. PG can occur anywhere on the body. Lesions often progress in size and may
be multiple. There is no universally accepted treatment for PG. In mild disease, therapy
consists of local wound care and topical or intralesional corticosteroids. For more severe
disease, systemic agents are necessary. Systemic corticosteroids are often effective, but
large doses are required leading to serious long-term side effects. Other
immunosuppressives have been reported to be successful in individual case reports and small
case series. However, they too are associated with significant toxicities.
Infliximab is an antibody directed against TNF-α. It had been used in success for treatment
of PG. Adalimumab (Humira) is a fully human antibody directed against TNF-α. Given that
adalimumab has the same target as infliximab, one would expect that adalimumab may also be
effective in the treatment of PG. Treatment with adalimumab may be advantageous over
infliximab because it can be given at home, whereas infliximab is delivered intravenously in
the office. Additionally, because adalimumab is fully human, patients would be less likely
to form antibodies against the medication. Purpose of this study is to determine the safety
and efficacy of Humira in the treatment of pyoderma gangrenosum.
- Subject is willing and able to give informed consent.
- Subject is willing and able to participate in the study as an outpatient and is
willing to comply with study requirements.
- Subject is 18 years of age or older.
- Subject has a diagnosis of pyoderma gangrenosum that involves total area of 3 cm2 or
greater and is of sufficient severity to warrant systemic agents.
- If female of childbearing potential, subject will have a negative urine pregnancy
test at Screening and Week 0.
- If female, subject will be either post-menopausal for > 1 year, surgically sterile
(hysterectomy or bilateral tubal ligation), or practicing one form of birth control
(abstinence, oral contraceptive, estrogen patch, implant contraception, injectable
contraception, IUD, diaphragm, condom, sponge, spermicides, or vasectomy of partner).
Female subjects will continue to use contraception for 6 months following the last
- Screening laboratory results are within the following parameters:
- Hemoglobin > 9 g/dL
- White blood cells > 3.0 x 10 to the 9th power/L, <14.0 x 10 to the 9th power/L
(unless on oral corticosteroids and no signs/symptoms of infection)
- Neutrophils > 1.5 x 10 to the 9th power/L
- Platelets > 100 x 10 to the 9th power/L
- Lymphocytes > 0.5 x 10 to the 9th power/L
- Serum creatinine within 1.5 times the upper limit of normal range
- AST and ALT within 2 times the upper limit of normal range
- Subject has been on a stable dose of antibiotics, oral corticosteroids or other
immunosuppressives, such cyclosporine, tacrolimus, azathioprine, methotrexate,
or mycophenolate mofetil over the previous 4 weeks
- Subject has evidence of a clinically significant, unstable or poorly controlled
- Subject has a chest X-ray consistent with an active infection or previous exposure to
TB and/or a positive purified protein derivative test at screening (>5 mm). (Subjects
may participate if they are being actively treated in accordance with CDC
- Subject has a serious, active or recurrent bacterial, viral, or fungal infection.
This includes hepatitis B and C, and HIV.
- Subject has been hospitalized for infection or received IV antibiotics within the
previous 2 months prior to baseline.
- Subject has clinical evidence as determined by the investigator of acutely infected
pyoderma gangrenosum or subject is receiving systemic antibiotics for the treatment
of acute infection. Subjects receiving minocycline, tetracycline, dapsone, or other
antibiotics for anti-inflammatory purposes are permitted.
- Subject has a history of tuberculosis without documented adequate therapy.
- Subject has a history of a central nervous system disorder/demyelinating disease or
symptoms suggestive of multiple sclerosis or optic neuritis.
- Subject has current signs or symptoms or history of systemic lupus erythematosus.
- Subject has been diagnosed with a malignancy within the past 5 years except for
successfully treated non-melanoma skin cancer.
- Subject has signs or symptoms suggestive of a possible lymphoproliferative disease.
- Subject has a diagnosis of severe congestive heart failure (Class III or IV NYHA).
- Subject has had a substance abuse problem within the previous 3 years.
- Subject has been treated with an anti-TNF biologic immune response modifier, such as
infliximab, adalimumab, or etanercept within the past 8 weeks.
- Subject has any dermatologic disease in the target site that may be exacerbated by
treatment or interfere with examination.
- Subject has been administered an investigational drug in another clinical study
within 30 days prior to baseline (or 5 half-lives, whichever is longer).
- Subject has a known allergy to adalimumab.
- Subject is female and is pregnant, is considering becoming pregnant during the study
and for 6 months afterwards, or is nursing.