low dose oral methotrexate in pediatric crohn's disease patients initiating anti-tumor necrosis factor (anti-tnf) therapy

Conditions: Pediatric Crohn's Disease

Summary: the purpose of this study is to determine whether adding low dose methotrexate to anti -tnf therapy is more effective than treatment with anti-tnf therapy alone in inducing and maintaining steroid-free remission for children with crohn's disease.

overall study duration: 6 years multi-center study: up to 42 centers number of subjects: 425 duration of treatment for each subject: up to 156 weeks (3 years) the primary endpoint is percent of patients who experienced treatment failure over time.

Eligibility criteria:
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 \< 12 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\ 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