Tocilizumab in the Management of Juvenile Idiopathic Arthritis Associated Uveitis

Inclusion Criteria:

- Subjects with Juvenile Idiopathic Arthritis

- Subjects with vision-threatening autoimmune uveitis.

- Failure to respond to methotrexate or at least one other systemic immunosuppressive or
intolerance to such medications due to side effects. Failure to respond includes
presence of one plus or greater anterior chamber cell in both eyes; need for topical
corticosteroid four times or more in either eye; ocular hypertension or glaucoma
attributable to the topical corticosteroid.

- Subjects with bilateral disease.

- If subjects are on oral corticosteroids, the dosage must be stable for 2 weeks prior
to baseline and not exceed 10 mg per day or 2mg/kg/day (whichever is less) of
prednisone or its equivalent. Subjects must be willing to agree to not alter the
dosage of oral steroids during the first 16 weeks of the trial.

- Must have a chest radiograph within 3 months prior to enrollment with no evidence of
malignancy, infection or fibrosis.

- Parent or guardian must understand and voluntarily sign an informed consent form.

- Pediatric subjects of either gender 2-17 years at time of consent.

Exclusion Criteria:

- Inability of parent or guardian to provide voluntary consent

- Major surgery (including joint surgery) within 8 weeks prior to screening or planned
surgery within 12 months following randomization.

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study

- Pregnant or breastfeeding

- Current liver disease, as determined by the Principal Investigator on the basis of
history or serum studies

- History of severe allergic or anaphylactic reactions to human, humanized or murine
monoclonal antibodies including tocilizumab.

- Evidence of significant uncontrolled concomitant diseases such as nervous system,
renal, hepatic (patients with prior history of ALT elevation will not be excluded),
endocrine, or gastrointestinal (GI) disorders, which in the Investigator's opinion,
would preclude patient participation.

- Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease
where flares are commonly treated with oral or parenteral corticosteroids.

- Any major episode of infection requiring hospitalization or treatment with IV
antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
screening

- History of active mycobacterial infection with any species (including Mycobacterium
tuberculosis) within 2 years prior to screening visit. Subjects with Mycobacterium
tuberculosis infection more than 2 years prior to screening visit are allowed if
successful treatment was completed at least 2 years prior to randomization and is
documented and available for verification.

- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline

- Latent Mycobacterium tuberculosis infection as indicated by a positive Purified
Protein Derivative [PPD] skin test. Subjects with a positive PPD skin test and
documented completion of treatment for latent TB are eligible. Subjects with a
positive PPD skin test and not treated or no documentation of completion of treatment
are ineligible.

- If QuantiFERON® test is performed instead of the PPD test, only those with a negative
QuantiFERON® test are allowed in the study.

- History of incompletely treated Mycobacterium tuberculosis infection as indicated by

- Subject's medical records documenting incomplete treatment for Mycobacterium
tuberculosis

- Subject's self-reported history of incomplete treatment for Mycobacterium
tuberculosis

- History of recurrent bacterial infection (at least 3 major infections resulting in
hospitalization and/or requiring intravenous antibiotic treatment within the past 2
years) or recurrent viral, fungal, mycobacterial, or other infections (including but
not limited to atypical mycobacterial disease, hepatitis B and C, and herpes zoster,
but excluding fungal infections of the nail beds)

- Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest x-rays
performed within 3 months prior to start of study drug are acceptable.

- Use of any investigational medication within 4 weeks prior to start of study drug or 5
pharmacokinetic/pharmacodynamic half-lives (whichever is longer)

- History of congenital or acquired immunodeficiency (eg, Common Variable
Immunodeficiency [CVID])

- Hepatitis B surface antigen positive or Hepatitis B core antibody positive at
screening

- History of Human Immunodeficiency Virus (HIV) infection

- Antibodies to Hepatitis C at screening

- Malignancy or history of malignancy (except for treated [ie, cured] basal-cell skin
carcinomas > 3 years prior to screening)

- Have multiple sclerosis or other central demyelinating disorder.

- Presence of a transplanted organ (with the exception of a corneal transplant performed
> 3 months prior to enrollment).

- History of substance abuse (drug or alcohol) within the previous 3 years, history of
noncompliance to medical regimens, or other condition/circumstance that could
interfere with the subject's adherence to protocol requirements.

- Previous or current use of an alkylating agent (e.g. chlorambucil or
cyclophosphamide).

- Treatment with etoposide (VP16) within 3 months prior to the baseline visit.

- Administration of intravenous immunoglobulin for the treatment of active polyarticular
disease within 4 weeks prior to the baseline visit.

- Previous treatment with any cell depleting therapies, including investigational agents
(e.g. anti-CD19 and anti-CD20).

- Prior stem cell transplant at any time.

- TNF -blocker use within the 8-weeks prior to enrollment (Infliximab use within 10
weeks prior to enrollment).

- Laboratory Exclusion criteria (at screening):

- Serum creatinine >1.5 ULN (upper limit of normal for age and sex);

- AST or ALT > 1.5 ULN (upper limit of normal for age and sex);

- Total bilirubin > 1.3 mg/dL (> 23 umol/L);

- Platelet count < 150 x 103/μL (< 150,000/mm3);

- Hemoglobin < 9.0 g/dL (< 3.7 mmol/L);

- WBC count < 5,000/mm3 (< 5.0 x 109/L);

- Neutrophil count < 2,500/ mm3 (< 2.5 x 109/L)