Precise Infliximab Exposure and Pharmacodynamic Control

Prior treatment

• Prior use of anti-TNF therapy (infliximab, adalimumab, certolizumab pegol, or golimumab)
• Active perianal abscess (receiving oral antibiotics for \<7 days)
• Intestinal stricture (luminal narrowing with pre-stenotic dilation \>3 cm) and surgery planned in the next 90 days
• Current ileostomy, colostomy, ileoanal pouch, and/or previous extensive small bowel resection (\>35 cm) or any CD surgery planned within the next 90 days
• Treatment with another investigational drug in the last four weeks
• Currently receiving treatment for histoplasmosis
• History of TB, human immunodeficiency virus (HIV), an immunodeficiency syndrome, a central nervous system demyelinating disease, history of heart failure or receiving intravenous antibiotics in last 14 days for any infection

Other illness

• Diagnosis of ulcerative colitis or inflammatory bowel disease-unspecified
• Internal (abdominal/pelvic) penetrating fistula(e) in last 180 days
• Have tested positive for Clostridium difficile toxin (stool assay) or other intestinal pathogens within 14 days of screening unless a repeat examination is negative and there are no signs of ongoing infection with that pathogen.
• Current hospitalization for complications of severe Crohn's disease
• History of autoimmune hepatitis, primary sclerosing cholangitis, thyroiditis, or juvenile idiopathic arthritis
• History of malignancy (including lymphoma or leukemia)
• Inability or failure to provide informed assent/consent

Other

• Intra-abdominal abscess/phlegmon/inflammatory mass in the last 180 days
• Planned use of methotrexate or 6-mercaptopurine (azathioprine) during the induction (first 3 doses of infliximab) phase
• Currently pregnant, breast feeding or plans to become pregnant in the next 1 year
• Any developmental disabilities that would impede providing assent/consent

• Written informed consent from the patient (≥18 years old) or from parent/legal guardian if patient is \<18 years old
• Written informed assent from patient when age appropriate
• Diagnosis of Crohn's disease within the last 90 days (luminal-only or luminal with a perianal fistula or abscess treated with antibiotics for at least 7 days)
• ≥6 years to ≤22 years of age, anti-TNF naïve and starting infliximab
• Clinical activity and luminal inflammation, defined by both (1) and (2)
  • (1) PCDAI≥10 (\<18 years old) or CDAI ≥150 (≥18 years old) in last 60 days before the decision to start infliximab
  • (2) SES-CD\>6, or SES-CD\>3 for isolated ileal disease (or a report of large intestinal ulcerations)\* within the last 60 days or a fecal calprotectin \>250 μg/g within last 75 days prior to screening
• C-reactive protein \>1.0 mg/dL in last 30 days and/or fecal calprotectin \>250 μg/g within last 75 days prior to screening
• Negative TB (tuberculosis) interferon-gamma release test and a negative urine pregnancy test for female patients (if menstruation has started)