None listed
Conditions
Brief summary
Chronic pouchitis is a common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Although antibiotics have been the mainstay of treatment for acute pouchitis, a proportion of patients become antibiotic-dependent or develop antibiotic-refractory pouchitis. There are few effective therapeutic options for these patients, and few prospective trials assessing their effectiveness. Tofacitinib was recently approved by Therapeutic Goods Administration (TGA) for treatment of ulcerative colitis (UC). It was found to be effective for induction and maintenance therapy in patients with moderate to severe UC. Chronic pouchitis is associated with similar inflammatory pathway activation as UC, therefore this study aims to investigate whether tofacitinib is effective for the treatment of chronic pouchitis.
Interventions
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
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
Sponsors
Pfizer Australia
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
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 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^ ^ Recommend pre-treatment vaccinations for hepatitis B, varicella zoster and mumps, measles, rubella if serology testing is negative. * Individuals with latent tuberculosis should be treated with standard antimycobacterial therapy before administering tofacitinib.
Exclusion criteria
1. Crohn’s disease of pouch (defined as the presence of stricture or fistula in the pouch) 2. IPAA surgery was performed for an indication other than ulcerative colitis such as familial adenomatous polyposis syndrome (FAP), hereditary nonpolyposis colorectal cancer, or Crohn’s disease (CD) 3. High cardiovascular risk factors (CHADS2 score > 2) 4. Bradycardia at baseline (<60 beats per minute), sick sinus syndrome, sinoatrial block, atrioventricular block 5. Chronic renal impairment (eGFR < 50mL/min) 6. Chronic liver disease (Child Pugh score B or C) or chronic hepatitis B 7. Active infections, including hepatitis B, hepatitis C, human immunodeficiency virus, varicella zoster virus, tuberculosis, mumps, measles and rubella 8. History of organ transplantation on immunosuppressive medications 9. Previous use of lymphocyte-depleting therapies (ie. alemtuzumab, cyclophosphamide, total lymphoid irradiation, rituximab, and any other lymphocyte depleting therapies) 10. History of unprovoked thromboembolism or hypercoagulable condition 11. Active or past malignancy (except non-melanoma skin cancer) or lymphoproliferative disorder 12. Significant lymphopenia (absolute lymphocyte count < 0.75x109cells/L), or neutropenia (absolute neutrophil count < 1.0 x109cells/L), or anaemia (hemoglobin < 80g/L) 13. Pregnancy or lactation 14. History of hypersensitivity or adverse events to other JAK inhibitor
Outcome results
None listed