Colitis,Ulcerative
Conditions
Keywords
Tumor Necrosis Factor-alpha/antagonists & inhibitors, Infliximab, Adalimumab, Golimumab, Recurrence
Brief summary
The primary objective is to assess if discontinuation of anti- tumor necrosis factor alpha (TNF) treatment in ulcerative colitis patients in sustained clinical remission, with the option to restart treatment in the case of relapse, is non-inferior to continued anti-TNF treatment. Secondary objectives are to assess the efficacy and safety of restarting anti-TNF treatment after a relapse
Detailed description
The BIOSTOP study is a prospective, open randomized, multicenter, parallel-group study to compare clinical outcome of discontinuing (interventional group) compared to continuing (control group) biologic treatment with anti-TNF in ulcerative colitis patients in clinical remission. Adult male and female patients with an established diagnosis of ulcerative colitis treated for minimum one year with anti-TNF maintenance therapy and being in clinical remission during the last 3 months are potential study patients. Eligible patients who have given their informed written consent will be randomized 1:1 to either discontinue anti-TNF treatment or to continue anti-TNF treatment for another two years. Patients in the control group who are still in clinical and endoscopic remission after two years on continued anti-TNF treatment, will then be switched to discontinue anti-TNF treatment. End of study/follow-up is after 4 years. In order to identify the primary endpoint (occurrence of disease relapse), each study center will have a phone number for patients to call in case of symptoms suspect of increased disease activity. If a patient is experiencing a potential disease flare (6-point Mayo score \> 1) and/or 2 consecutive calprotectin tests are positive (\> 200 mg/kg), an unscheduled visit including recto sigmoidoscopy will be performed without delay to document disease status. 150 participants enrolled, September 2020 Covid 19 - randomization period extended until 31.12.2020
Interventions
OTHERDiscontinuation of anti-TNF treatment
Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences
OTHERContinuation of anti-TNF treatment
Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue
Sponsors
Oslo University Hospital
University of Oslo
Helse Møre og Romsdal HF
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* confirmed diagnosis of ulcerative colitis * treated for minimum 1 year with first-line anti-tumor necrosis factor (TNF) treatment * in sustained clinical remission during the last 3 months * capable of understanding and signing an informed consent form
Exclusion criteria
* Discontinuation of systemic 5-Aminosalicylic acid (ASA) or immunomodulatory therapy or other medication that could affect disease activity during the last 3 months prior to randomization * Any treatment of systemic corticosteroids due to disease exacerbation during the last 3 months (i.e. patients being in steroid free clinical remission) * Patients on anti-TNF monotherapy with intolerance to both 5-ASA and immunomodulatory therapy * Change in the anti-TNF treatment during the last 3 months due to disease related factors, not including dose/frequency adjustments due to drug concentration measurements * Use of any second-line anti-TNF medication irrespective of reason for stopping first-line anti-TNF * Previous failed attempts of anti-TNF discontinuation of more than 4 months' duration, with the exception of discontinuation due to pregnancy * Detection of anti-TNF antibodies in moderate-high titers prior to randomization * Psychiatric or mental disorders * Alcohol abuse or other substance abuse * language barriers or other factors which makes adherence to the study protocol impossible * Participation in any other studies * pregnancy * breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients in sustained clinical remission | 2 years | Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of relapse patients achieving remission after anti-TNF restart | 2 years | Remission after relapse |
| Proportion of patients in sustained clinical remission | 4 years | Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment |
| Time from randomization to relapse | 2 years | Relapse time |
| Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy | 2 years | Remission, but no need to restart anti-tnf therapy |
| Adverse events and serious adverse events frequency and severity | 2 years | Adverse events |
Countries
Norway
Outcome results
None listed