management of moderate postoperative recurrence in crohn's disease: a randomized controlled trial of therapeutic escalation, the pomerol trial. (pomerol)

Conditions: Crohn Disease

Summary: study type : a 30 months, multicentre, open-label strategic randomized controlled trial population : chron's disease (cd) patients with an i2 endoscopic postoperative recurrence in the year following ileocolonic resection (6-12months after ileocolonic resection). treatments : stratification at inclusion according to prophylactic therapy. patients randomized in 2 arms: * status quo arm: if the patient received no prophylactic therapy, no treatment will be started; if the patient received a prophylactic therapy, the same will be continued at the same dose. * therapy escalation arm: infliximab-ct-p13 will be started with two intravenous infusions of 5 mg per kg bodyweight at week 0 and week 2 and subcutaneous injections of 120 mg every 2 weeks from week 6 onwards. main objective : to evaluate the proportion of cd patients without endoscopic postoperative recurrence (i0-i1) at 12 months in the arm receiving therapy escalation compared to status quo arm in patients having an i2 endoscopic postoperative recurrence 6-12months after ileocolonic anastomosis with restoration of faecal stream.

number of patients : 360 patients in approximatively 25 sites in france. recruitement period : the trial duration for each patients will be 12 months from radomization (18 to 24 months from screening (ie : post-operatively)) endpoints: primary endpoints: proportion of patients with an i0-i1 modified rutgeerts score at 12 months. secondary endpoints: * proportion of patients with an i3-i4 modified rutgeerts score at 12 months * proportion of patients with an i2b-i3-i4 modified rutgeerts score at 12 months * proportion of patients with an i0 modified rutgeerts score at 12 months * pro2 score at 12 months * clinical postoperative recurrence within 12 months: average daily sf ≥ 3.5 and average daily ap score ≥ 1.5, and * increased crp compared to inclusion, at least + 10 mg/l * or increased fecal calprotectin compared to inclusion, at least + 250 μg/g * surgical recurrence within 12 months: need for a new ileocolonic resection * endoscopic dilatation within 12 months: need for a balloon insufflation at the ileocolonic anastomosis during an ileocolonoscopy when a non-passable stenosis was present in patient having obstructive symptoms (cdos \> 4) before endoscopy * time to clinical postoperative recurrence * serious adverse events * quality of life: eq5d-5l questionnaire * work productivity: work productivity and activity impairment questionnaire

Eligibility criteria:
inclusion criteria: * crohn's disease diagnosed according usual criteria * bowel resection with ileocolonic anastomosis performed removing all inflammatory lesions * postoperative endoscopy performed between 6 and 12 months after ileocolonic anastomosis reaching the neoterminal ileum (patients who underwent a two stage surgical procedure are also eligible if the endoscopic evaluation is performed 6-12 months after restoration of the fecal stream) * moderate endoscopic postoperative recurrence classified i2 according to the rutgeerts score at 6-12 months, validated by a blinded central reading exclusion criteria: * patients with an ostomy * ulcerative colitis or ibd type unclassified * ileorectal or ileal pouch-anal anastomosis * symptoms defined as average daily sf ≥ 3.5 and average daily ap score ≥ 1.5 having started after a free interval without symptoms of at least one month after surgery * patients with obstructive symptoms of cd defined by a cdos \> 4 * patients exposed to infliximab before index surgery with a primary non-response (no clinical effect after 2 infusions at the discretion of the treating gastroenterologist) or history of infusion reactions to infliximab or history of detectable anti-infliximab antibodies * patients treated with biological therapy (except for intraocular injections) or an investigational medical product after index surgery * patients having started thiopurines or methotrexate more than 6 weeks after ileocolonic anastomosis with restoration of the fecal stream * patients in whom not all inflammatory lesions have been removed at index surgery * patients with active perianal crohn's disease * patients with a contraindication to infliximab: cancer in the 5 years prior to inclusion excluding non-melanoma skin cancer, active tuberculosis or untreated latent tuberculosis, moderate or severe heart failure, hiv or hbv infection (serology \< 6 months), recent live vaccination (within 4 weeks of baseline) * pregnant women * patients under legal protection or unable to express their consent. * patients not affiliated to a health insurance system. * patients deprived of liberty by judiciary or administrative decision or hospitalized without consent or admitted in a sanitary or social institution for another reason than research.

Keywords: crohn's disease rutgeerts score i2 infliximab ct-p13 postoperative reccurrence ileocolonic resection