A randomized, placebo-controlled pilot study to determine endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or ileocolonic surgery in patients receiving post-operative infliximab or placebo

Inclusion Criteria:

• men/women > 18 years of age
• curative resection/ileocolonic anastomosis for Crohn's disease
• may have received previously received infliximab
• if on oral aminosalicylates or corticosteroids, dose must be stable for 4 weeks prior to surgery
• if on 6-mercaptopurine,azathioprine or methotrexate,individual must have been on it for minimum of 3 months prior to surgery with stable dose for 4 weeks
• men and women must use adequate birth control for duration of study and for 6 months after receiving the last infusion
• antibiotics for treatment of Crohn's disease must be discontinued within 12 weeks after surgery; antibiotics are allowable throughout study as long as primary purpose of antibiotic therapy is not for primary treatment of Crohn's disease
• screening lab results must meet screening criteria (hemoglobin = or > 8.5g/dL; Serum glutamic oxaloacetic transaminase ,3 times upper normal limit,platelets =or> 100 x 10 9th/L; lymphocytes count =or> 0.5 x 10 9th/L and neutrophils =or> 1.0 x 10 9th/L
• have a documented negative reaction to a purified protein derivative skin test performed within 3 months prior to baseline
• have a normal chest radiograph results within 3 months prior to baseline
• are capable of providing written informed consent and obtained prior to conducting any protocol-specified procedures
• willing to adhere to the study visit schedule and other protocol requirements
• are considered eligible according to the tuberculosis eligibility assessment, screening and early detection of reactivation rules
• patients who undergo resective surgery and primary ileocolonic anastomosis with a temporary ileostomy upon takedown of the diverting ileostomy.

Exclusion Criteria:

• patients with greater than 10 years of Crohn's disease requiring first resection of a short (<10cm) fibrostenotic stricture
• macroscopically active disease at anastomosis at time of surgery
• presence of stoma
• prior severe infusion reaction to infliximab
• history of anaphylaxis to murine products or other chimeric proteins
• any of the following medications taken within 12 weeks of surgery: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, investigational drugs, or medications targeted at reducing tumor necrosis factor
• have a positive stool culture for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin and have clinically significant signs of an enteric infection at screening
• women who are pregnant, nursing or planning pregnancy during the trial or within 6 months after the last infusion
• patient with active tuberculosis, patient newly diagnosed with latent tuberculosis who's receiving tuberculosis prophylaxis, patient with recent close contact to individual with active tuberculosis
• have or have had opportunistic infection within 6 months of screening
• have chest radiograph within 3 months prior to screening that shows malignancy, infection, or abnormalities suggestive of tuberculosis
• documentation of seropositive for HIV
• documentation of a positive test for hepatitis B surface antigen or a history of documented hepatitis C
• have current signs/symptoms of systemic lupus erythematosus, or severe progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral diseases
• presence of a transplanted solid organ (with exception of corneal transplant > 3 months prior to randomization)
• Have any current or known malignancy or have history of malignancy within 5 years of screening(except for squamous or basal cell carcinoma of the skin that has been fully excised with no evidence of recurrence)
• have history of lymphoproliferative disease or splenomegaly
• have known substance abuse(drug/alcohol)/dependency within the previous 3 years, history of noncompliance with medical regimens, or other condition that may interfere with adherence to protocol requirements
• are unwilling/unable to undergo multiple venipunctures because of poor tolerability or lack of easy access
• known history of demyelinating disease
• a chronic or recurrent infectious disease
• serious infection, hospitalization for infection, or treatment with IV antibiotics for infection within 2 months prior to randomization
• a serious concomitant illness that may interfere with participation in trial
• concomitant diagnosis/history of congestive heart failure
• current use of prescription doses or chronic/frequent use of non-steroidal anti-inflammatory drugs
• ulcerative colitis
• concurrent participation in another investigative trial
• use of any investigational drug within 30 days prior to randomization

12 months

Limitations to our study included a small sample size, a disproportionate number of smokers in the infliximab group, more patients on immunomodulators in the placebo group, and inclusion of patients who had previously received infliximab.