Colitis, Ulcerative
Conditions
Brief summary
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
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.
Interventions
DRUGAzathioprine
AZA treatment after IFX withdrawal for maintenance of remission
DRUGInfliximab
IFX treatment for maintenance of remission
Sponsors
Agenzia Italiana del Farmaco
Istituto Clinico Humanitas
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized parallel two-arm prospective open-label study
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse rate | 12 months | relapse rate in the two study groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relapse time | 12 months | Mean time to relapse in the two groups |
| Number of adverse events [Safety and Tolerability] | 12 months | Number of adverse events of the two study strategies |
| Number of serious adverse events [Safety and Tolerability] | 12 months | Number of serious adverse events of the two study strategies |
| Identification of potential risk factors for relapse. Age, sex, smoking habits, histological healing of mucosa and each Mayo subscore at baseline will be examined | 12 months | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Direct costs [Pharmacokinetics] | 12 months | Direct costs of the two treatment strategies |
Countries
Italy
Contacts
Primary ContactSilvio Danese, MD, PhD
Backup ContactGionata Fiorino, MD, PhD
Outcome results
None listed