This study will investigate the safety and effectiveness of the drug TNFR:Fc to treat
uveitis (eye inflammation) in patients with juvenile rheumatoid arthritis. In other
studies, TNFR:Fc significantly reduced joint pain and swelling in adult patients with
rheumatoid arthritis, and the Food and Drug Administration has approved the drug for that
use. Because medicines for arthritis often help patients with eye inflammation, this study
will examine whether TNFR:Fc can help patients with uveitis.
Patients with uveitis who are not responding well to standard treatment, such as steroids,
and patients who have side effects from other medicines used to treat their uveitis or have
refused treatment because of possible side effects may be eligible for this study.
Candidates will be screened with a medical history, physical examination, and eye
examination. The eye exam includes a check of vision and eye pressure, examination of the
back of the eye (retina), and front of the eye, including measurements of protein and
inflammation. Candidates will also undergo fluorescein angiography-a procedure in which
photographs are taken of the retina to see if there is any leakage in the eye's blood
vessels. A blood test and joint evaluation will also be done.
Study participants will be given a shot of TNFR:Fc twice a week for up to 12 months and may
continue other medicines they may be taking, such as prednisone or methotrexate. They will
have follow-up examinations at week two and months one, two, three and four. Those who wish
to continue treatment after the fourth month can receive the drug for another eight months
and will have follow-up exams at months six, nine and 12, and one month after treatment
ends. Each follow-up visit will include a repeat of the screening exams and an evaluation
of side effects or discomfort from the medicine.
Current treatment modalities for uveitis associated with Juvenile Rheumatoid Arthritis (JRA)
including corticosteroids and other immunosuppressive agents are associated with significant
side effects. These treatments are not effective for all children. A soluble tumor
necrosis factor receptor (TNFR:Fc) named Etanercept, may inhibit the inflammatory response
of uveitis. This randomized double-masked phase I/II clinical trial will provide limited
safety and efficacy information regarding the use of Etanercept for the treatment of uveitis
associated with JRA. Fifteen patients will be randomized with a 2 to 1 randomization plan
(10 to receive Etanercept, 5 to receive placebo) and followed for 6 months. After the 6
month visit, all patients will receive open label Etanercept for an additional 6 months.
Patients will be switched to open label Etanercept, or withdrawn from study therapy prior to
6 months, if they a) experience a greater than 10 letter or greater drop in visual acuity
due to inflammation, for patients using the ETDRS chart (a 2 line drop due to inflammation,
for patients using the B-VAT method) or b) develop a sight-threatening inflammatory
ophthalmic or joint lesion requiring immediate increase in systemic anti-inflammatory
therapy or a periocular injection of corticosteriods or c) at 4 months, have greater than 1
plus anterior chamber cell grade in either eye and are receiving topical corticosteroids on
a schedule of TID or more frequently. Investigators will remain masked to original
treatment assignment unless warranted by clinical care considerations. Primary safety
outcomes include the occurrence of any severe adverse event at least possibly related to
study therapy, including a two step increase in anterior chamber cells, or the occurrence of
serious infection or sepsis. Primary ophthalmic outcomes include measures of anterior
chamber cells and a change in topical or systemic anti-inflammatory medications used to
treat uveitis. Primary ophthalmic and JRA outcome analysis will be performed at 6 months,
and again at 12 months. Patients unmasked or switched to open label Etanercept prior to
month 6 or withdrawing from the study drug prior to month 12 will be considered failures.
Meet American College of Rheumatology Criteria for JRA.
Have active anterior uveitis defined as the presence of inflammatory cells (Grade 1+ or
higher) in the anterior chamber of at least one eye or the current use of topical
corticosteroids to control exacerbation of disease at a frequency of TID or higher.
Be between 2 and 18 years, inclusive.
Be able to undergo slit lamp biomicroscopy for assessment of anterior chamber cells.
Be able to comply with study requirements.
Be up to date on all recommended childhood immunizations.
Have been using current arthritis regimen for at least 8 weeks prior to enrollment.
Have a media opacity that precludes assessment of anterior chamber inflammation.
Have a periocular injection of corticosteroids within 2 months of baseline, or used a
systemic experimental therapy within one month of baseline evaluation.
Be currently receiving disease modifying antirheumatic therapy (DMARD), with the exception
of prednisone at a dose no greater than 1.0 mg/kg/day, or methotrexate at a dose no
greater than 15 mg/m(2)/week.
Have active eye or joint inflammation requiring immediate addition or increase in systemic
Be a Female who is pregnant or lactating .
Refuse to use contraception during the study and 6 months after termination of active
study therapy, if child-bearing or fathering potential exists.
Have used Latanoprost within two weeks prior to enrollment, or have a current or likely
need for Latanoprost during the course of the study.
Have hypersensitivity to fluorescein dye.
Have active serious infections or history of recurring serious infections.
Evidence of spondyloarthropathy or entheseopathy.