Two Therapeutic Strategies for the Maintenance of Remission in Patients With Ulcerative Colitis

Study Overview
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Brief Summary
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Ulcerative colitis patients treated with Infliximab (IFX) in deep remission after at least 12 months of treatment will be randomized to continue IFX or to stop IFX and start Azathioprine (AZA). Each patient will be followed for 12 months.

Detailed Description
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All eligible subjects will be able to participate in the study at any infusion occurred after 12 months since the beginning. They will be screened by medical history, physical examination, blood and faecal tests (included C-reactive protein and faecal calprotectin), as required by clinical practice. No children, pregnant or breastfeeding women, or elder subjects will be included. A colonoscopy + biopsies in the area of greater inflammation will be performed within ± 3 weeks since the baseline visit. The subjects can then be randomized and receive their first dose of study medication. Subjects will be then evaluated every 8 weeks for the following 12 months from the randomization. Clinical and blood tests will be performed, and the partial Mayo Score will be calculated at each visit, until the final visit, when a new colonoscopy with biopsies will be repeated and the global Mayo Score will be evaluated. At final visit a new faecal sample for calprotectin will be collected. Safety of the study treatments will be evaluated at each study visit. In case of study agent discontinuation, the patient will be managed according to usual practice and followed for the entire study period. Patients randomized in AZA arm, could restart IFX.

Official Title
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Comparison Between Two Therapeutic Strategies for the Maintenance of Clinical and Endoscopic Remission in Patients With Ulcerative Colitis Treated by Infliximab

Conditions
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Colitis, Ulcerative

Intervention / Treatment
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* Drug: Azathioprine
* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 -65 years Written informed consent and willing to adhere to study procedures. Therapy with infliximab since at least 12 months, with one infusion every 8 weeks (a maximum interval between two infusions of ± 3 weeks is allowed) Sustained steroid-free remission in the last 6 months prior to inclusion, except for use of steroids as a preventive measure for infliximab infusion reaction, if required by local guidelines. Global Mayo score at baseline ≤ 2 All Mayo subscores ≤ 1 Absence of rectal bleeding Effective methods to avoid pregnancy during the study period Exclusion Criteria: Disabling and persisting extraintestinal manifestation at baseline Patients unable to comply with study procedures Known intolerance or previous allergic reaction to thiopurines Concomitant therapy with allopurinol Any disease not compatible with the use of infliximab or azathioprine, as per clinician's judgement. Need for dose escalation of infliximab in the last 12 months prior to baseline. White blood cell count < 3000/mmc or absolute clinically relevant lymphopenia at baseline Active pregnancy or breastfeeding; willing for pregnancy during the study period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized parallel two-arm prospective open-label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Azathioprine<br>Azathioprine 2-2.5 mg/kg/day, according to approved indication | Drug: Azathioprine<br>* AZA treatment after IFX withdrawal for maintenance of remission<br>|
| Active Comparator: Infliximab<br>Infliximab 5 mg/kg every 8 weeks | Drug: Infliximab<br>* IFX treatment for maintenance of remission<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rate | relapse rate in the two study groups. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse time | Mean time to relapse in the two groups | 12 months | 
| Number of adverse events [Safety and Tolerability] | Number of adverse events of the two study strategies | 12 months | 
| Number of serious adverse events [Safety and Tolerability] | Number of serious adverse events of the two study strategies | 12 months | 
| Identification of potential risk factors for relapse. Age, sex, smoking habits, histological healing of mucosa and each Mayo subscore at baseline will be examined | Potential risk factor for relapse will be evaluated by univariable analysis, and a multivariable analysis will be performed for all factors with p<0.30. Risk factors will be also analysed by logistic regression. Analysis of predetermined baseline characteristics (age, sex, smoking habits, histological healing of mucosa at baseline, and each Mayo subscore (stool number, presence of blood, colonic ulcerations) excluding the physician global assessment) to identify predictive factors for relapse. | 12 months |