Stelara fOr ChRonic AntibioTic rEfractory pouchitiS

This study is a Belgian prospective open label multicenter study to evaluate the efficacy and safety of ustekinumab in the treatment of relapsing or chronic antibiotic refractory pouchitis during a 48-week treatment period. Twenty subjects with a RPC and IPAA for UC who have developed relapsing or chronic antibiotic refractory pouchitis will be enrolled.

All patients will receive intravenously (IV) ustekinumab ~6mg/kg at baseline and subcutaneously (SC) ustekinumab 90mg every 8 weeks thereafter until Week 48. All subjects will receive concomitant antibiotic treatment with ciprofloxacin or metronidazole from baseline through Week 4. Intravenous induction doses will be 260mg for patients <55kg, 390mg for patients between 55 and 85kg, and 520mg for patients with a body weight >85 kg.

Clinical and biochemical evaluation will be planned every 8 weeks. Efficacy will be assessed at Week 16 and Week 48 using mPDAI and PDAI scores, therefor a pouchoscopy with biopsy sampling will be performed. Patients who do not achieve partial response (reduction of mPDAI score by ≥2 points from baseline) at Week 16 will be discontinued.

Inclusion criteria

• The subject has a history of ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC)
• The subject has pouchitis that is (a) relapsing or (b) chronic antibiotic refractory, defined by an mPDAI score ≥5 assessed as the average from 3 days immediately prior to the baseline endoscopy visit and a minimum endoscopic subscore of 2 (outside the staple or suture line) with either (a) ≥3 recurrent episodes within the last year, each treated with ≥2 weeks of antibiotic or other prescription therapy, or (b) requiring maintenance antibiotic therapy taken continuously for ≥4 weeks immediately prior to the baseline endoscopy visit

Exclusion criteria

• Crohn's disease (CD), CD-related complications of the pouch (pouch fistula, pouch strictures, ulcerations in the pre-pouch ileum without pouchitis), irritable pouch syndrome (IPS), isolated or predominant cuffitis, infectiouw pouchitis, diverting ostomy or mechanical complications of the pouch
• Previous treatment with an anti-IL12/23 or an anti-IL23 antibody
• Any investigational or approved biologic agent within 30 days of baseline
• Nonbiologic investigational therapy or tofacitinib within 30 days prior to baseline
• Active or untreated latent tuberculosis (TB)
• Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, a known history of human immunodeficiency virus (HIV) infection (or is found to be seropositive at screening) or subject is immunodeficient
• Active severe infection (e.g. sepsis, cytomegalovirus, listeriosis or C. difficile)
• History of malignancy or current malignancy