A study to assess the efficacy of tofacitinib for the treatment of chronic pouchitis in adults

INTERVENTION: An open label induction with randomized, double blind, placebo‐controlled withdrawal trial The study comprises two phases: An 8‐week induction phase, with optional 8‐week extension for non‐responders, followed by a 24‐week maintenance phase. During the induction phase, all participants will receive oral tablets of tofacitinib 10mg twice daily dosing for 8 weeks. At the end of induction, non‐responders will proceed to extended induction, receiving another 8 weeks of tofacitinib 10mg twice daily dosing. Responders to standard or extended induction will proceed to randomization (1:1 allocation), to either oral tofacitinib 5mg twice daily or placebo (identical appearing oral tablet BD) during maintenance phase. The non‐responders at the end of extended induction phase will discontinue from study. Any participants who experience a flare of symptoms would proceed to the open label extension study for 12 weeks, receiving either 5mg or 10mg twice daily dosing of tofacitinib, at the treating physician’s discretion. A total of 5 study visits are planned during the follow up period, including 3 pouchoscopies to assess pouch inflammation. At each of the study visits, there are several measurement tools involved, including study visit review, blood and stool tests, as well as questionnaires CONDITION: Chronic pouchitis; ; Chronic pouchitis Inflammatory and Immune System ‐ Autoimmune diseases Oral and Gastrointestinal ‐ Inflammatory bowel disease PRIMARY OUTCOME: The primary outcome is the proportion of patients with a clinical response to tofacitinib at the end of maintainence phase compared to placebo in patients with chronic pouchitis. This is evaluated using the validated modified Pouchitis Disease Activity Index (mPDAI) scoring system.[End of maintenance phase, which is 24 weeks post randomisation.] SECONDARY OUTCOME: Antibiotic free remission, by assessing patient medical records[At end of maintenance phase (24 weeks post randomisation)] Change in inflammatory biomarkers, including faecal calprotectin and C‐reactive protein[At the end of induction phase ( 8 weeks post commencement of study)] Change in inflammatory biomarkers, including faecal calprotectin and c‐reactive protein[At the end of maintenance phase (24 weeks post randomisation)] Change in quality of life using validated questionnaire tools: ; 1. Short Inflammatory Bowel Disease Questionnaire (SIBDQ) ; 2. Patient‐Reported Outcomes Measurement Information System (PROMIS‐29) ; 3. Oresland Score ; [At the end of induction phase (8 weeks post commencement of study)] Change in quality of life using validated questionnaire tools: ; 1. Short Inflammatory Bowel Disease Questionnaire (SIBDQ) ; 2. Patient‐Reported Outcomes Measurement Information System (PROMIS‐29) ; 3. Oresland Score[At the end of maintenance phase (24 weeks post randomisation)] Clinical remission (a total mPDAI < 5) [At the end of induction (8 weeks post commencement of study)] Clinical response (a reduction of modified Pouchitis Disease Activity Index of >2) [End of induction phase (week 8 post commencement of study)] Corticosteroid free remission, by assessing patient medical records ; INCLUSION CRITERIA: 1. Adult patients age 18 to 65 2. Previous diagnosis of ulcerative colitis (UC) and have undergone total proctocolectomy and ileal pouch‐anal anastomosis (IPAA) 3. Chronic or recurrent pouchitis that required > 4 weeks of antibiotics (CADP) in the previous 12 months OR pouchitis that is refractory to antibiotic therapy (CARP) 4. A total modified pouchitis disease activity index (mPDAI) score > 5 with endoscopic evidence of active disease ^ Recommend pre‐treatment vaccinations for hepatitis B, varicella zoster and mumps, measles, rubella if serology testing is negative. ; [At the end of maintenance phase (24 weeks post randomisation)] Endoscopic response (a reduction of endoscopic Pouchitis Disease Activity Index of > 2) [At the end of induction (8 weeks post commencement of study)] The safety profile over the course of the study, including pouch failure, adverse events and serious adverse events. This will be assessed through patient medical records[At the each study visits throughout study period] 5. Completed pre‐screening tests (blood test and chest x‐ray) for tofacitinib therapy, including hepatitis B^, hepatitis C, human immunodeficiency virus, varicella zoster virus^, tuberculosis*, mumps^, measles^ and rubella^ * Individuals with latent tuberculosis should be treated with standard antimycobacterial therapy before administering tofacitinib.