Safety and Efficacy of a Stopping Strategy versus Standard Maintenance Dose of JAK Inhibitors in Adults with Deep Remission Ulcerative Colitis (Randomized Controlled Trial)

The primary objective is to determine whether a discontinuation strategy for JAK inhibitors is superior to continued maintenance dosing in adult patients with ulcerative colitis who are in deep, steroid‑free remission, by evaluating treatment safety, efficacy, patient‑reported satisfaction, and overall drug exposure. Secondary objectives include:

• Assessing the overall safety profile of both treatment arms throughout follow‑up.
• Measuring remission rates at week 52.
• Evaluating treatment satisfaction across efficacy, side‑effects, convenience and global domains using the TSQM 1.4 at week 52 and during extended follow‑up.
• Determining therapeutic success at weeks 52 and 104.
• Monitoring clinical remission over the entire study period.
• Quantifying the number of steroid‑free remission days at week 52.
• Quantifying total JAK inhibitor exposure and exposure to high‑dose induction therapy during the first 52 weeks.
• Assessing health‑related quality of life at weeks 52 and 104.
• Evaluating endoscopic outcomes at weeks 52 and 104.
• Analyzing relapse rates in relation to the treatment strategy.
• Identifying predictive factors for response to the stopping strategy.

The trial enrolled adult individuals (≥ 18 years) of both sexes who had a confirmed diagnosis of ulcerative colitis for at least six months and were in deep remission while receiving a JAK inhibitor for more than 12 months. Participants were required to be on a stable dose of tofacitinib, upadacitinib, or filgotinib for at least six months, to have maintained steroid‑free clinical remission (partial Mayo score < 2, rectal bleeding subscore 0) for a minimum of six months, and to demonstrate endoscopic remission (Mayo endoscopic subscore 0) and fecal calprotectin ≤150 µg/g at screening. General health status had to be good based on history and clinical examination, and subjects were excluded if they had known risk factors for malignancy, venous thromboembolism, or major adverse cardiovascular events. Women of child‑bearing potential and men with partners of child‑bearing potential were required to use effective contraception. The sponsor did not provide the total number of participants enrolled.

The study is a multicenter, randomized, double‑blind, controlled trial evaluating a stopping strategy versus conventional maintenance dosing of ulcerative colitis JAK inhibitors in adults who have maintained deep remission for at least six months. After an initial screening visit to confirm eligibility, participants are randomized 1:1 to either taper and discontinue the JAK inhibitor or continue the standard maintenance dose. Study medication is administered orally as tofacitinib, upadacitinib, or filgotinib at the established stable dose. Participants attend study visits at baseline (randomization), weeks 4, 12, 24, 36, 52, 78, and 104, with each visit collecting safety data, clinical indices, endoscopic assessment, fecal calprotectin, and patient‑reported outcomes. The primary observation period lasts 52 weeks, and the overall follow‑up extends to 104 weeks, resulting in a participant involvement of approximately two years. Early termination may occur if a participant experiences a serious adverse event, meets predefined failure criteria, or withdraws consent. Recruitment began in July 2026 and the trial is planned to conclude in July 2030.

The investigational arm may include filgotinib supplied as Jyseleca 200 mg film‑coated tablets for oral administration. The prescribed dose is 200 mg taken once daily. Tablets are to be ingested with water, and dosing is maintained at a stable level for a minimum of six months prior to randomization. Compliance is assessed by tablet count at each visit and by electronic diary entries documenting daily intake.

Another possible investigational product is tofacitinib provided as XELJANZ 5 mg film‑coated tablets for oral use. The protocol specifies a total daily dose of 40 mg, administered as the appropriate number of tablets once daily. Tablets are swallowed whole with water. Adherence monitoring includes pill count, patient‑reported dosing logs, and periodic verification of plasma drug concentrations when feasible.

The trial also permits the use of upadacitinib in the form of RINVOQ 45 mg prolonged‑release tablets, taken orally once daily. The 45 mg tablet provides a sustained release of the active substance throughout the dosing interval. Dosing consistency is ensured through scheduled dispensing, pill counts, and electronic compliance tracking.

Participants assigned to the comparator arm continue their established maintenance regimen of the same JAK inhibitor at the dose that achieved deep remission, without alteration of formulation or administration schedule. This standard‑of‑care approach serves as the non‑experimental control for evaluating the stopping strategy.

Efficacy will be evaluated through a composite of clinical, endoscopic, and patient‑reported outcomes in adult participants with ulcerative colitis who are in deep remission. The primary efficacy parameters include remission rate at week 52, treatment success defined by the absence of failure criteria at week 52 and week 104, and the proportion of patients experiencing relapse during the follow‑up.

Clinical disease activity will be monitored using the Partial Mayo score at each study visit, providing a time‑dependent pattern of change throughout the trial. Endoscopic disease activity will be assessed by the Mayo endoscopic subscore at week 52 and week 104. Patient‑reported efficacy will be captured by the efficacy dimension of the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), with the area under the curve calculated over the first 52 weeks and the full 104‑week period. Additional quality‑of‑life instruments include the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), the Inflammatory Bowel Disease‑Disability Index (IBD‑DI), and the SF‑36 health survey, administered at weeks 52 and 104.

All efficacy assessments will be performed using validated scales at predefined timepoints: baseline, each scheduled clinic visit, week 52, and week 104. Data will be collected electronically, processed according to the statistical analysis plan, and analyzed using appropriate longitudinal and categorical methods to compare the stopping strategy with the classical maintenance dose.