Adalimumab for the Management of Post-operative Crohn's Disease (CD) (POPART)

Inclusion Criteria:

• 18-70 years old at the time of screening
• Male or female
• Firs ileocolonic surgical resection (
• Evidence of both macroscopic as well an microscopic evidence of Crohn's disease in the resected intestinal segment
• Patient able to undergo pre randomization screening no earlier then 14 days and no later then 45 days post operatively.
• Patients may receive anti-TNF-agents (i.g. infliximab or adalimumab)previously
• Patients may receive corticosteroids, 6MP/AZA, methotrexate, or mesalamine prior to surgery.
• Antibiotics, or mesalamine, must be discontinued within the screening/baseline 4 week period. Patients on steroids may be enrolled as long as steroids are tapered off.
• Remission as defined by a CDAI ≤ 150.
• Women of childbearing potential, and men, must use medically acceptable methods of contraception [surgical sterilization, IUD, hormonal preparations, or double barrier method (e.g. condom or diaphragm, and spermicide)] throughout the study and for a period of 6 months after receiving the last injection.
• Screening lab results must be within prespecified limits: Hemoglobin ≥ 8.8 g/dl; SGOT/SGPT < 3 X the upper limit of normal; Neutrophil count ≥ 1.0 X 109/L & lymphocyte cont of ≥ 0.5 X 109/L
• Must have a documented PPD ≤ 5 mm, in patients taking steroids, within the month before randomization, or taking immunomodulators 2 months prior to randomization. Other patients must have documented PPD ≤ 10 mm prior to randomization. PPD must be preformed and documented by an appointed member of the investigatory stuff. Patients must have a normal chest radiograph (both posterior-anterior and lateral views), read by a certified radiologist, within 3 months prior to randomization.
• Commitment to adhere to study protocol requirements
• Negative stool cultures for enteric pathogens (Salmonella, Shigella, Campylobacter, Ova & parasites), and negative clostridium difficile toxin assay in stool.
• Patients are able to self-inject or have a designee or healthcare professional who can inject the study medication at the appropriate intervals.
• Patient's with long standing (>5Y), as well as recently diagnosed Crohn's disease ,will be eligible if they show radiologic (i.e. CT enterography, MR enterography , small bowel follow through) evidence, as well as laboratory (i.e. CRP, platelets level, fecal calprotectin, ESR ) evidence for an active inflammatory process within a 3 months period prior to the qualifying surgery

Exclusion Criteria:

• evidence of macroscopic inflammatory disease at the surgical margins or else ware, according to the surgeon
• Patients who discontinued anti TNF-alpha agents due to loss of efficacy or tolerability issues.
• Patients with temporary ileostomy.
• Patients with longstanding quiescent CD undergoing surgery for the treatment of a fibrostenotic lesion, without an active inflammatory disease process in the resected segment.
• Any of the following medications taken within 3 months prior to randomization: cyclosporine, tacrollimus, mycophenolate mofetil, or other investigational anti-inflammatory agents. Medication targeting the reduction of TNF-alpha (infliximab, golimumab, cetrolizumb pegol, etanercept), natalizumab, or other FDA approved biological agents may be administered up until to index surgery.
• Patient who have an ongoing active infection within the baseline period: intra-abdominal abscess, enteric infection as determined by stool cultures for bacteria, parasites and clostridium difficile toxin, other serious systemic bacterial infection within 3 months before randomization (e.g. Pneumonia; pyelonephritis; meningitis).
• Patients with active TB, patients in close contact to individuals with active TB, patients with latent TB whether receiving or not receiving prophylaxis.
• Patient that have or had an opportunistic infection within the last 6 months
• Patients seropositive to HIV, HBV, or HCV. Patients will be actively screened for HBV vaccination, and will be required to undergo vaccination according to international guidelines.
• Patients having current signs/symptoms of severe or progressive systemic disease: any progressive/uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or psychiatric illness.
• Patients after organ transplantation
• Any current or known malignancies
• Use of any investigational drug within 60 days prior to randomization
• Current/frequent use of NSAIDS (i.e. regular use of NSAIDS for more than 3 times a week for longer than 7 consecutive days during the trial period).
• Pregnant or lactating women
• Concomitant substance or alcohol abuse
• Subjects unable to self-inject or do not have a designee or healthcare professional who can inject the study medication.
• Subject unable to comply with the planned schedule of study visits and study procedures.
• Patients with short bowel syndrome
• Patients with previous small bowel surgeries