Polyarticular juvenile idiopathic arthritis (Poly JIA) is a form of juvenile arthritis, which is a chronic disease affecting approximately 250,000 people younger than 16 years of age. Poly JIA can be treated with anti-tumor necrosis factor (anti-TNF), a type of medication that is often effective but also has some toxic side effects and is expensive. Among those with poly JIA who are effectively treated with anti-TNF, some can remain healthy off the medication, but some begin to feel the effects of their disease again once the medication is stopped. This study will attempt to find whether certain tests or signs can predict which people with poly JIA can safely stop their anti-TNF medications.

Juvenile arthritis is a chronic disease affecting approximately 250,000 people younger than 16 years of age in the United States. Its symptoms include swelling, pain, and damage in the joints. Juvenile arthritis can take four different forms, including poly JIA. Poly JIA affects five or more joints, generally the smaller ones in wrists and fingers, causing stiffness, joint damage, and sometimes eye inflammation in the children and adolescents who suffer from it. Approximately 30% of people with juvenile arthritis have Poly JIA.

Treatment for juvenile arthritis involves drugs with escalating strength, depending on what each individual responds to best. The first treatment option is non-steroidal anti-inflammatory drugs (NSAIDs), such as Motrin IB and Aleve. The second treatment option is methotrexate (MTX). About 30% to 50% of poly JIA patients are effectively treated with MTX. Only if the patient does not respond to MTX is an anti-TNF drug used. Anti-TNF drugs often result in profound disease improvement, but unfortunately, they can have toxic side effects and are expensive.

For people whose poly JIA is inactive or minimally active on MTX or anti-TNF drugs, 50% to 80% experience a worsening of symptoms once they stop taking the medications. Most of these flare-ups occur within 8 months of stopping treatment. Currently, there is no way to predict which people with poly JIA can safely stop anti-TNF medications. This study will evaluate two different factors-levels of certain calcium binding proteins and production of TNF-for their use in predicting whether people with poly JIA are likely to experience a disease flare-up once they stop anti-TNF treatment. The study will also look for genetic markers that can serve as predictors of safe discontinuation of anti-TNF treatment.

Participation in this study will last up to 14 months and involve up to nine study visits. Visits will be conducted at study entry and after 3, 6, 7, 8, 9, 10, 12, and 14 months. The first three study visits will involve tests to determine baseline health indicators and to ensure inactive disease. If, after 6 months, participants continue to have inactive disease, they will be taken off their anti-TNF medications. For the remainder of the study, visits will be used to monitor disease activity. If participants experience any clinically defined disease flare-ups, they will immediately stop participating in the study and begin additional treatment as prescribed by their health care providers. At all study visits, participants will undergo a general physical examination, a joint examination, questionnaires about how the disease affects their lives, and blood collection for research samples.

Inclusion Criteria:

• Diagnosis of polyarticular JIA (rheumatoid factor + and rheumatoid factor -) or extended oligo JIA by the International League of Associations for Rheumatology (ILAR) criteria
• Receiving therapy with one of the currently available anti-TNF biologics: infliximab, etanercept, or adalimumab
• Absence of any of the FDA label exclusions for anti-TNF therapy
• Receiving slit lamp exams performed at regular intervals in accordance with the published American Academy of Pediatrics guidelines
• Baseline hemoglobin >10 g/dl
• Absence of joints with active arthritis, using the American College of Rheumatology (ACR) definition of "active joint"
• Absence of fever, rash, serositis, splenomegaly, or generalized lymphadenopathy attributable to JIA
• Absence of active uveitis, as per an exam by an ophthalmologist
• Normal erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP); if above normal range, must be not attributable to JIA
• Physician's global assessment of disease activity indicating absence of disease activity, defined as the best score obtainable on the scale used
• Duration of morning stiffness less than or equal to 15 minutes

Exclusion Criteria:

• Diagnosis of a type of JIA other than polyarticular JIA
• Diagnosis of another inflammatory disease that may affect laboratory results or ability to discontinue anti-TNF biologic therapy
• Concurrent treatment with any biologic agent other than infliximab, etanercept, or adalimumab
• previous treatment with rituximab
• concurrent treatment for JIA with corticosteroids >0.2 mg/kg/day OR >10 mg/day

deidentified subject information and results of testing have already been shared with multiple investigators requesting samples