Een studie om te bepalen of vedolizumab ( een medicijn) beter helpt dan een placebo om de terugkeer van de ziekte van Crohn te stoppen na verwijdering van de zieke darm.

Study Design:

This multi-centre randomized placebo-controlled study will look into the effect of vedolizumab to prevent recurrence of CD after ileocolonic resection. All patients will undergo an ileocolonoscopy at week 26 following surgery (in line with current recommendations). The endpoint is the proportion of patients with clinically significant recurrence of CD (Modified Rutgeerts Grade 2b, 3 or 4) after 6 months after surgery.

In most centers across the world, patients in the postoperative phase are routinely undergoing ileocolonoscopy 6 months after surgery. To justify a 50% placebo-arm, we will exclude patients with an unfavorable disease course or severe perianal fistulas.



Primary endpoint:

Proportion of patients with severe endoscopic postoperative recurrence of CD (Rutgeerts i2b, i3 or i4) 6 months after ileocolonic resection with anastomosis (stoma excluded).

It has been established that the endoscopic Rutgeerts’ score is a strong surrogate marker for the further clinical course of the disease (see appendix for scoring system). All endoscopies will be video-recorded for later review and central re-reading.



ACCRUAL AND FEASIBILITY

This study will enroll 80 subjects at 13 sites in The Netherlands, Spain, France and Italy. The feasibility of enrollment in this study is highly plausible given the high rates of resections at these academic centres and lack of alternative treatments.



TREATMENT, DOSAGE AND ADMINISTRATION

Patients will be consented to participate with 2-3 weeks following ileocolonic resection. The first study-infusion will also be given within 2-3 weeks if all inclusion and exclusion criteria are met. Patients will receive intravenous infusions of 300 mg of VDZ or 250 ml or 0,9% sodium chloride only (placebo) at Week 0, Week 8, Week 16 and 24.



PERMITTED CONCOMITANT MEDICATIONS

Loperamide or cholestyramine for control of bile acid diarrhea Prednisone will be tapered over 4 weeks postoperatively All other medications will be discontinued postoperatively.

Postoperative recurrence of CD (Crohn's disease) is very common in patients having undergone bowel resection, and often leads to further bowel resection. Postoperative recurrence is frustrating to both the physician and patient, and thus an effective strategy to prevent CD recurrence without unwanted side effects is warranted. The reduced incidence of CD recurrence with TNF (tumor neucrosis factor) inhibitor treatment is promising as a therapeutic option, however development of antibodies to anti-TNF biologics and the potential need for dose escalation suggests that an alternative therapeutic option with a different mode of action would be welcome. The efficacy of VDZ (vedolizumab) in the induction and maintenance of remission in CD suggests that VDZ holds potential for preventing CD recurrence following bowel resection. This investigator-initiated study will assess this possibility.

Primary outcome : week 26-28



Proportion of patients without endoscopic recurrence (i0) : week 26-28

Symptomatic recurrence (CDAI increase >70 points compared to baseline) : at baseline and every 8 weeks before infusion

Proportion of patients with normalized serum CRP at all time points and CRP at all visits : at baseline and every 8 weeks before infusion

Proportion of patients with normal fecal calprotectin (<50) : at all visits

- Quality of life measured by IBDQ and SF-36 : at baseline and every 8 weeks before infusion

- Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion : at all infusion visits before infusion.

Vedolizumab 300 milligram 8 weekly (4 doses) or placebo 8 wekkly (4 doses)