Infliximab to Treat Children With Juvenile Rheumatoid Arthritis

INCLUSION CRITERIA:

Age: Patients must be less than 18 years of age and greater than or equal to 4 years of age.

Diagnosis of pauciarticular, polyarticular or systemic onset JRA according to the 'Criteria for the diagnosis of Juvenile Rheumatoid Arthritis' with evidence of active disease including all of the features within each category:

Pauciarticular JRA (if patients continue to develop a polyarticular course):

1. active synovitis involving at least 4 swollen joints
2. tenderness or pain on movement of greater than 4 involved joints

Polyarticular JRA:

1. active synovitis involving at least 4 swollen joints
2. tenderness or pain on movement of greater than 4 swollen joints
3. elevated acute phase reactants (ESR greater than 20mm/hr or CRP greater than 0.8mg/dl)

Systemic onset JRA (if patients develop a polyarticular course):

1. active synovitis involving at least 4 swollen joints
2. tenderness or pain on movement of greater than 4 swollen joints
3. elevated acute phase reactants (ESR greater than 20mm/hr or CRP greater than 0.8mg/dl)

Disease onset at age less than16 years.

Informed Consent: All parent(s) or their legal guardian(s) must sign a document of informed consent indicating their understanding of the investigational nature and the risks of this study before any protocol related studies are performed (this does not include routine laboratory tests or imaging studies required to establish eligibility). Pediatric patients will be included in all discussions in order to obtain verbal or written assent.

All patients enrolled must have an incomplete response to methotrexate at a dosage of at least 0.75 mg/kg/week or a maximum of 25 mg/week orally or subcutaneously for a minimum of 12 weeks.

No other disease modifying anti-rheumatic drugs will be allowed while on study. Patients on combination DMARD therapy will have all DMARDs (except methotrexate) withdrawn at least 2 weeks prior to trial initiation. Patients must be off etanercept for 4 weeks prior to enrolling in this study.

Stable doses of non-steroidal anti-inflammatory drugs including selective Cox-2 inhibitors. Patients enrolling should be on stable NSIAD doses for at least 2 weeks. If currently not on NSAIDs, patients must not have been using them for 2 weeks.

Stable dose of prednisone (or equivalent amount of any other corticosteroid) equal or less than 0.4 mg/kg/day for at least four weeks. If currently not on corticosteroids, patients must not have been using them for 4 weeks.

Subject has negative PPD.

If anergy control skin tests and PPD are negative, Infectious Disease (ID) will be consulted and if cleared by the ID the patient will be included into the study.

EXCLUSION CRITERIA:

Pregnant women and nursing mothers, sexually active men or women of childbearing potential not practicing birth control. (Sexually active subjects of childbearing or child-fathering potential must be willing to use an acceptable form of birth control, which includes oral contraceptives, barrier methods with spermicides, intrauterine devices (IUD's), medroxyprogesterone acetate (Depo-Provera), progestin implants or intrauterine system or surgical sterilization. All post-menarche females or females greater than or equal to 12 years must test negative on a urine pregnancy test. Sexually active males and females will be instructed to use condoms).

Patients with other rheumatic diseases that may confound the analysis including but not limited to Lyme disease, post streptococcal reactive arthritis, psoriatic arthritis, spondyloarthropathy, systemic lupus erythematosus, other infectious or reactive arthritis, or Reiter's syndrome.

Previous treatment with iv infliximab at doses greater than 3mg/kg/dose every 8 weeks.

Poor venous access.

Treatment with any monoclonal antibody in the past other than infliximab.

Allergy to murine-derived products.

Previous history or ongoing infection with tuberculosis or pneumocystis and patients with acute or chronic infections requiring anti-microbial therapy, serious viral infections (e.g. hepatitis, herpes zoster, CMV or HIV) or fungal infections or history of recurrent serious bacterial infections.

History of live vaccinations within the past 3 months.

Confounding medical illness that in the judgment of the investigators would pose added risk for study participants (e.g. chronic hepatic, hematologic, neurologic, renal, or pulmonary disease).

Past medical history or be currently diagnosed with any solid organ or hematologic malignancies including lymphoproliferative diseases and leukemias.

History of substance abuse within the past 5 years.

History of psychiatric illnesses that in the opinion of psychiatric consultants would pose added risk for study participants.

Pre-existing or recent onset of demyelinating disorders or type I diabetes.