Low Dose Oral Methotrexate in Pediatric Crohn's Disease Patients Initiating Anti-Tumor Necrosis Factor (Anti-TNF) Therapy

Overall study duration: 4 years Multi-center study: up to 42 centers

Number of subjects: 425 Duration of treatment for each subject: up to 104 weeks (2 years)

The primary endpoint is time to treatment failure.

Inclusion Criteria:

- Pediatric Crohn's Disease (PCD) patients, < 21 years of age, ≥20 kg, initiating
anti-TNF therapy with infliximab or adalimumab (including biosimilars).

- Diagnosis of Crohn's Disease (CD) established confirmed by the treating clinician, and
established by standard clinical criteria (radiography, endoscopy, histology).

- Ability to provide parental permission and child assent (where applicable), or adult
consent for patients ages 18-20.

Exclusion Criteria:

- Prior use of anti-TNF or other biological therapy for CD

- Lack of stable home address that study medications can be mailed to

- Anticipated short length of follow up at study center (plans for family to move,
transition to adult GI (gastrointestinal) provider, etc.). Patients expected to leave
practice < 24 months from enrollment should not be enrolled.

- Concurrent pelvic or abdominal abscess. A recent history of abdominal or pelvic
abscess, which is controlled, does not exclude the subject.

- Prior intra-abdominal surgery without a clinically significant relapse (i.e. patients
starting on anti-TNF for post-op prophylaxis or for endoscopic recurrence only should
not be included)

- Receipt of a live virus vaccine within the last 30 days

- Pregnancy, planning to become pregnant, or high risk of pregnancy as determined by the
local investigator

- Breastfeeding

- Refusal to stay abstinent or utilize 2 forms of birth control while on study
medication (for female patients)

- BMI > 98% for gender and age

- Known previous or concurrent malignancy (other than that considered surgically cured,
with no evidence for recurrence for 5 years). A recent history of basal cell or
squamous cell carcinoma, which is considered surgically cured, does not exclude the
subject.Those with a recent history of colonic adenoma or dysplastic lesions should be
excluded.

- Known high alcohol consumption (more than seven drinks per week)

- Patients with serum albumin < 2.5 g/dl

- Patients with white blood cell count (WBC) < 3.0 x109th/L

- Patients with platelet count < 100 x109th/L

- Patients with initial elevation of liver enzymes (AST or ALT) > 1.5 times above normal
limit

- Patients with known active infection with Clostridium difficile (C. difficile)
(untreated infection based on clinician assessment does not apply to colonization or
infection controlled with current or prior treatment.)

- Patients with pre-existing hepatic disease

- Patients with pre-existing renal dysfunction (creatinine > 0.8 for children age<10,
creatinine > 1.2 mg/dl for children age 10-18, and creatinine > 1.5 mg/dl for adults
age 18 years and older).

- Patients with a pre-existing chronic lung disease other than well controlled asthma

- Current treatment with one of the following drugs: Probenecid (Probalan), Acitretin
(Soriatane), Streptozocin (Zanosar), Azathioprine (Imuran, Azasan), 6-mercaptopurine
(Purinethol, Purixan)

- Other concerns about the patient/family's ability to participate in the study