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

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.

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.