Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not?

Continuing or Discontinuing Anti-tumor Necrosis Factor Treatment in Patients With Ulcerative Colitis in Clinical Remission: a Prospective Open Randomized Parallel-group Study

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

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

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