Safety and Efficacy of a STOPping Strategy Versus Classical Maintenance Dose of JAK Inhibitors in Deep Remission Patients With Ulcerative Colitis

Official title

Safety and Efficacy of a STOPping Strategy Versus Classical Maintenance Dose of JAK Inhibitors in Deep Remission Patients With Ulcerative Colitis: a Randomized Controlled Trial

Overview

This phase IV, multicenter, open-label randomized controlled trial will evaluate whether a JAK inhibitor discontinuation strategy is superior to standard maintenance therapy in adult patients with ulcerative colitis who are in sustained deep remission. A total of 224 patients treated with tofacitinib, upadacitinib, or filgotinib will be randomized to either treatment withdrawal or continuation of maintenance therapy and followed for 104 weeks. The primary objective is to compare safety, efficacy, and patient satisfaction at Week 52, while secondary objectives include assessment of remission maintenance, quality of life, treatment exposure, endoscopic outcomes, and relapse rates

Detailed description

Background:

Janus kinase (JAK) inhibitors are effective oral therapies for moderate-to-severe ulcerative colitis (UC). Their lack of immunogenicity provides a unique opportunity to evaluate treatment withdrawal and intermittent treatment strategies. However, safety concerns raised by regulatory agencies, including increased risks of infections, venous thromboembolism, major adverse cardiovascular events, and malignancies, support the investigation of strategies aiming to reduce long-term exposure to JAK inhibitors while maintaining disease control.

Objective:

To demonstrate the superiority of a JAK inhibitor stopping strategy compared with standard maintenance therapy in terms of treatment safety, efficacy, and patient satisfaction in adults with ulcerative colitis in deep remission.

Study Design:

This is a phase IV, prospective, multicenter, open-label, randomized controlled trial. Adult patients with ulcerative colitis receiving a stable dose of tofacitinib, upadacitinib, or filgotinib for at least 12 months and achieving sustained steroid-free clinical, biological, and endoscopic remission for at least 6 months will be randomized to either treatment discontinuation or continuation of standard maintenance therapy. A total of 224 participants will be enrolled and followed for 104 weeks.

Primary Endpoint:

The primary endpoint is a composite outcome assessing treatment safety, efficacy, and patient satisfaction during the first 52 weeks after randomization. Patient satisfaction will be evaluated using the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4).

Secondary Endpoints:

Secondary outcomes include adverse events and serious adverse events, maintenance of remission, treatment satisfaction, quality of life, JAK inhibitor exposure, endoscopic outcomes, relapse rates, treatment success at Weeks 52 and 104, and identification of predictors of successful treatment discontinuation.

Expected Benefits:

Reducing exposure to JAK inhibitors may improve the overall safety profile by decreasing treatment-related adverse events while reducing treatment burden for patients with ulcerative colitis. This strategy could support a more individualized and potentially safer long-term management approach for patients in sustained deep remission.

Interventions

• Drug treatment withdrawal
  the patients will stop their treatment, as long as possible until symptom reappearance, if any

Primary outcome measures

• The primary endpoint of this study will be a composite criterion of treatment safety, efficacy, and patient satisfaction during the first 52 weeks of the follow-up. [Time frame: 1 year]
• The primary endpoint of this study will be a composite criterion of treatment safety, efficacy, and patient satisfaction during the first 52 weeks of the follow-up. [Time frame: 1 year]
• The primary endpoint of this study will be a composite criterion of treatment safety, efficacy, and patient satisfaction during the first 52 weeks of the follow-up. [Time frame: 1 year]

Secondary outcome measures (8)

• Safety: occurrence of herpes zoster, infection, cardiovascular event, biochemical parameter, malignancies, adverse event leading to discontinuation, and all adverse events (serious or not) during the whole follow-up. [Time frame: 2 years]
• Remission rate at the end the first 52 weeks of the follow-up [Time frame: 1 year]
• Assess the treatment success of this innovative therapeutic strategy at the end of the first 52 weeks of the follow-up and after 104 weeks of follow-up. [Time frame: 2 years]
• Partial Mayo score at each visit of the entire follow-up [Time frame: 2 years]
• Number of days under treatment and cumulative dose of treatment per patient between randomization and primary endpoint [Time frame: 1 year]
• Number of days under induction dose of JAK inhibitor at the end the first 52 weeks of the follow-up. [Time frame: 1 year]
• Mayo endoscopic subscore at week 52 and week 104 [Time frame: 2 years]
• Proportion of patients relapsing for each arm [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Diagnosis of UC from at least 6 months according to clinical, endoscopic, histological and/or radiological criteria.
• Male or female age ≥ 18 years
• Currently treated by JAK inhibitor (tofacitinib, upadacitinib or filgotinib) for more than 12 months.
• Currently at a stable dose of tofacitinib (5mg or 10mg twice a day), upadacitinib (15mg or 30mg per day) or filgotinib (200mg per day) for 6 months.
• Clinical steroid free remission for at least 6 months, defined by a partial Mayo Score < 2, with no subscore > 1 and rectal bleeding (RB) subscore of 0 (annex 1).
• Endoscopic steroid free remission for at inclusion, defined by a Mayo endoscopic subscore = 0 (annex 1).
• Fecal calprotectin ≤ 150μg/g.
• Without known risk factors for venous thromboembolism (VTE).
• Without known risk factors for major adverse cardiovascular events (MACE).
• Without known risk factors for malignancy.
• For women of child-bearing potential (WOCBP), and for men with partners who are WOCBP, willingness to use appropriate and efficient contraception, as recommended when using JAK inhibitor treatment (notably upadacitinib), during all the experimental treatment and until at least 4 weeks after the end of the experimental treatment, according to SmPC and CTFG (Clinical Trials Facilitation and Coordination Group) recommendations.
• Patients able to understand information provide to them and to give written informed consent for study.
• Affiliation to a social security scheme.
• Good general health according to history and clinical examination.

Exclusion criteria

• Steroid use ≤ 6 months prior to enrolment.
• Currently treated by steroid, immunosuppressive agents or biologics.
• Pregnancy or planned pregnancy during the study.
• Breastfeeding.
• Non-compliant subject or inability to follow study protocol.
• Intolerance of JAK inhibitors (excipients included) or severe adverse event.
• Contraindications to using a JAK inhibitor (excipients included).
• Known risk factors for VTE.
• Known risk factors for MACE.
• Active neoplasia or history of malignant tumours less than 5 years old.
• Participation to another interventional study protocol (except for RIPH3 studies)
• Severe hepatic insufficiency.
• Severe to end-stage renal insufficiency.
• Active tuberculosis, serious infections such as septicemia or opportunistic infections.
• Absence or refusal of informed consent.
• People under guardianship, conservatorship, or judicial protection;
• People receiving psychiatric care;
• People who have been deprived of their liberty by judicial or administrative order
• People with difficulty understanding and/or cognitive disorder

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 22 centers

• CHU Amiens-Picardie — Amiens
• Centre Hospitalier d'Avignon — Avignon
• CHRU Besançon — Besançon
• CHU Bordeaux — Bordeaux
• CHU Clermont Ferrand — Clermont-Ferrand
• Chu Lille — Lille
• HCL — Lyon
• AP-HM hopital Nord — Marseille
• … and 14 more centers

Identifiers

NCT: NCT07718529 · RCAPHM24_0353 - STOP · 2026-525643-32-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗