Immunosuppressant Discontinuation in Elderly Patients With Ulcerative Colitis And Long-term Remission

Official title

Switching to Mesalazine Monotherapy vs Continuing Thiopurines in Older Patients With Ulcerative Colitis in Sustained Remission: A Multicenter Randomized Controlled Trial (IDEA)

Overview

IDEA is a Phase IV, prospective, randomised, open-label, multicentre clinical trial designed to evaluate the safety and efficacy of withdrawing thiopurines in elderly (≥60 years) patients with ulcerative colitis (UC) who are in sustained clinical and biological remission. The study compares discontinuation of thiopurines versus continuation while maintaining background mesalamine therapy over 24 months of treatment.

Detailed description

Study population and total sample size:

304 patients aged ≥ 60 years with ulcerative colitis in sustained clinical remission while on long-term thiopurine therapy.

Treatment strategies Group 1 - Continuation of thiopurines (± baseline oral mesalazine). Group 2 - Discontinuation of thiopurines and initiation/maintenance of oral mesalazine at a dose of 4 g/day.

Patients will attend a screening visit, a baseline visit (Day 0), and subsequently follow-up visits every 4 months until month 24. Fecal calprotectin will be measured at each visit according to standardized and validated procedures. The occurrence of relapse will lead to discontinuation of the patient's participation in the trial. Thereafter, rescue therapy will be initiated at the investigator's discretion and outside the scope of the study.

Interventions

• Drug Discontinuation of thiopurines.
  Because thiopurine-related toxicity rises with age while late-onset UC tends to be less aggressive, replacing thiopurines with high-dose oral mesalazine (≥ 3 g/day) may preserve remission and simultaneously reduce long-term oncological and infectious risks.

Primary outcome measures

• Biologic Relapse at 24 Months in Elderly UC Patients After Thiopurine Discontinuation [Time frame: From enrollment to the end of treatment suspension at 24 months.]

Eligibility criteria

Inclusion criteria

• Male or female patients aged ≥60 years at screening.
• Established diagnosis of ulcerative colitis according to ECCO criteria.
• Clinical and endoscopic remission ≥12 months (Mayo score ≤2, subscore ≤1) according to clinical practice.
• Treatment with a thiopurine (azathioprine 1-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) for ≥60 months. Treatment at stable doses (minimum effective dose without adverse events in the last 12 months.
• In case of concomitant treatment with oral mesalazine, the dose must´ve been stable for ≥12 months.
• Clinical remission (at the discretion of the investigator) for at least 3 years, without the need for treatment with oral or intravenous steroids or biological agents (topical rectal treatments are permitted as well as oral mesalazine if the dose has remained stable over the past 12 months).
• Colonoscopy performed within 6 months prior to the start of the study in endoscopic remission (Mayo endoscopic index 0) according to clinical practice.
• Two consecutive (centralised determinations in the period of one month) basal faecal calprotectin values <150 mg/kg during screening.
• Written informed consent.

Exclusion criteria

• Ulcerative proctitis (maximum observed extension <25 cm throughout the course of the disease)
• History of colectomy or imminent need for surgery.
• Presence of ileoanal reservoir
• History of complex perianal disease
• Intolerance to oral 5-ASA treatment
• Previous or concomitant biologic anti-TNF (vedolizumab, Ustekinumab) or JAK-inhibitor therapy for any condition.
• Severe chronic renal insufficiency, defined as serum creatinine ≥ 2 mg/dL (estimated glomerular filtration rate ≤ 30 mL/min/1.73 m²).
• Abnormal hepatic laboratory parameters, defined as AST, ALT, alkaline phosphatase, or GGT > 2X the upper limit of normal (ULN) at screening.
• Hematologic abnormalities at screening, defined as any of the following: absolute neutrophil count < 1,500 cells/mm³, lymphocytes < 500 cells/mm³, platelets < 120,000 cells/mm³, or haemoglobin < 12 g/dL (females) / < 13 g/dL (males).
• Any condition that in the investigator's opinion may compromise study participation.

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

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07248644 · IDEA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗