Gastroenterology · Medical Literature
Study of TOfacitinib for the treatment of chronic PouchITis (STOPit): a multi-centre open label induction with randomised, double blind, placebo-controlled maintenance trial.
Abstract
Study of TOfacitinib for the treatment of chronic PouchITis (STOPit) is a national, investigator-led, multicentre, open-label induction with randomised, double-blind, placebo-controlled maintenance trial to determine the effectiveness of tofacitinib to induce and maintain clinical remission in chronic pouchitis patients. The primary objective of STOPit is to evaluate the clinical response to tofacitinib, compared with placebo, using the validated modified Pouchitis Disease Activity Index score. Secondary objectives include clinical response and remission rates, endoscopic response and mucosal healing rates in induction and maintenance phases; rates of flare and recapturing response in open label extension phase; the effect of tofacitinib on clinical biomarkers and quality of life; and safety of tofacitinib use for treatment of chronic pouchitis. Study period is up to ten months, with five visits and three pouchoscopies. Adults with ulcerative colitis who have undergone total proctocolectomy and ileal pouch-anal anastomosis and have chronic pouchitis are eligible. Participants receive open-label 10 mg two times per day tofacitinib for 8 weeks. Clinical responders at the end of week 8 will be randomised to either tofacitinib or placebo in the maintenance phase. Non-responders will receive extended induction dosing for a further 8 weeks. Persistent non-responders exit the study and responders will proceed to maintenance randomisation. Randomised individuals will be followed for 24 weeks. Patients experiencing a flare of symptoms during the maintenance phase will be eligible to receive open-label tofacitinib. Efficacy and safety data will be evaluated at 12 weeks after termination from the study. Target sample size is 72 patients to be randomised into maintenance to achieve sufficient power. Data analysis is planned to commence in October 2026. Ethics approval was granted (Project ID 66809) and the trial was notified (CTN: CT-2020-CTN-04866-1; ANZCTR: 381128) prior to commencement. The study will be conducted in accordance with National Health and Medical Research Council (NHMRC) guidelines, and findings will be published in a peer-reviewed journal. CTN: CT-2020-CTN-04866-1.
Clinical relevance
Chronic pouchitis following total proctocolectomy with ileal pouch-anal anastomosis (IPAA) in ulcerative colitis patients represents a therapeutically challenging, often refractory condition with limited evidence-based treatment options beyond antibiotics and biologics. The STOPit trial addresses a critical evidence gap by systematically evaluating tofacitinib — an oral JAK1/JAK3 inhibitor already approved for UC — in this surgically-altered, difficult-to-treat population for whom no approved therapies currently exist. Gastroenterologists and colorectal surgeons managing post-IPAA patients require robust randomised controlled data to guide escalation of therapy beyond empirical antibiotic regimens.
Key findings
1. Study design: National, investigator-led, multicentre, open-label induction phase followed by a randomised, double-blind, placebo-controlled maintenance phase — representing a rigorous methodological framework for this orphan indication. 2. Induction dosing: All eligible participants receive open-label tofacitinib 10 mg twice daily for 8 weeks, with clinical response assessed at week 8 using the validated modified Pouchitis Disease Activity Index (mPDAI). 3. Non-responders at week 8 receive an extended induction course for a further 8 weeks before re-assessment, with persistent non-responders exiting the study — acknowledging variable induction kinetics in this population. 4. Maintenance phase: Clinical responders are randomised to tofacitinib versus placebo for 24 weeks, with a flare rescue arm allowing re-initiation of open-label tofacitinib during maintenance. 5. Target sample size: 72 patients randomised into the maintenance phase to achieve adequate statistical power; total study duration per participant is up to 10 months with 5 clinic visits and 3 pouchoscopies. 6. Secondary endpoints include endoscopic response, mucosal healing rates, clinical biomarker profiles, health-related quality of life, and comprehensive safety surveillance — with efficacy and safety data evaluated at 12 weeks post-study termination; data analysis planned to commence October 2026. NOTE: No interim efficacy, effect size, confidence interval, p-value, or NNT/NNH data are available in this protocol publication.
Practice implications
Clinicians managing UC patients with chronic pouchitis post-IPAA who have failed conventional antibiotic or biologic therapy should be aware of STOPit as a potential referral pathway, given the current absence of approved pharmacological options for this indication. The protocol's use of tofacitinib 10 mg twice daily — consistent with the induction dosing approved for moderate-to-severe UC — provides a pharmacologically rational basis for off-label consideration in refractory cases, though prescription should be deferred pending trial results given unquantified benefit-risk in this surgical subpopulation. Endoscopic assessment (pouchoscopy) with mPDAI scoring should be incorporated into routine follow-up of chronic pouchitis patients to align with emerging trial endpoints and ensure objective, reproducible disease monitoring that will facilitate interpretation of STOPit's forthcoming findings.