The purpose of this study is to determine the safety and efficacy of Humira in the treatment
of cutaneous sarcoidosis.
Sarcoidosis is a multisystem disease. Cutaneous involvement occurs in approximately 25% of
patients with lesion morphologies varying widely. There is no universally accepted
treatment for sarcoidosis. Systemic agents such as oral corticosteroids are frequently
necessary for treatment, but long-term therapy is limited by a multitude of serious adverse
effects. Steroid-sparing agents such as methotrexate, azathioprine, anti-malarials,
pentoxifylline, allopurinol, and thalidomide have been shown beneficial for select patients,
but are limited due to significant toxicities of their own or inconsistencies in efficacy.
Infliximab is a chimeric, monoclonal antibody directed against TNF-α and is currently
approved by the US Food and Drug Administration (FDA) to treat rheumatoid arthritis,
ankylosing spondylitis, and Crohn's disease. Etanercept is a dimeric fusion protein
consisting of the extracellular ligand-binding domain of the human TNF receptor linked to
the Fc portion of human IgG1. Etanercept has been approved for the treatment of psoriasis,
psoriatic arthritis, rheumatoid arthritis, and juvenile rheumatoid arthritis. Treatment
with infliximab and etanercept was generally well tolerated and safe in these reports.
To date, there have been no reports describing the treatment of sarcoidosis with adalimumab.
Adalimumab (Humira; Abbott Laboratories, Abbot Park, IL) is a fully human, monoclonal
antibody directed against TNF-α and is approved by the US FDA to treat rheumatoid arthritis.
Given that adalimumab targets the same cytokine as infliximab and etanercept, one would
expect that adalimumab may also be effective in the treatment of sarcoidosis. Treatment
with adalimumab is advantageous over infliximab through differences in drug delivery.
Infliximab is delivered intravenously in the office. This requires routine office visits
and vital sign monitoring by a health care professional.
Adalimumab, on the other hand, is administered subcutaneously once weekly or every other
week by the patient at home. Patients can be instructed on proper injection technique
during one nurse visit. Additionally, because adalimumab is fully human, patients may be
less likely to form antibodies against the medication. Because of the lack of alternative
safe, effective treatment for sarcoidosis, a clinical trial to evaluate the efficacy of
adalimumab in the treatment of sarcoidosis is warranted.
- 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 cutaneous sarcoidosis for greater than 6 months with a
physician global assessment score of at least 4. Diagnosis (based on the
recommendations of an expert panel 24) can be made by either:
- Skin lesions characteristic of sarcoidosis and a biopsy showing granulomas with
no evidence of mycobacteria, fungus, or malignancy.
- A biopsy that does not show granulomas, but the patient has characteristic skin
lesions and another clinical feature suggesting sarcoidosis (bilateral hilar
adenopathy, erythema nodosum, uveitis, raised ACE level, BAL lymphocytosis
(CD4:CD8>3.5), panda/lambda sign on gallium scan)
- 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 10to 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, thalidomide, antimalarials, 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
medical condition including unstable systemic sarcoidosis.
- 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).
- 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 a history of tuberculosis at anytime or close contact with a person with
active tuberculosis within the previous 6 months.
- Subject has received a live vaccination within the previous 3 months.
- 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 any dermatologic disease in the target site that may be exacerbated by
treatment or interfere with examination.
- 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 been treated with topical corticosteroids, tacrolimus, or pimecrolimus
within 2 weeks or intralesional corticosteroids within 4 weeks of baseline.
- 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.