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

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

Study Overview

• Status: Completed
• Conditions: Colitis,Ulcerative
• Intervention / Treatment: Other: Discontinuation of anti-TNF treatment; Other: Continuation of anti-TNF treatment

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

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Alesund, Norway
    • Helse Møre og Romsdal, Ålesund Sjukehus
  • Bergen, Norway, 5009
    • Haraldsplass Diakonale Sykehus
  • Bergen, Norway
    • Haukeland Universitetssykehus Helse Bergen HF
  • Forde, Norway
    • Helse Førde, Førde Sentralsjukehus
  • Fredrikstad, Norway
    • Sykehuset Østfold HF Kalnes
  • Hamar, Norway
    • Sykehuset Innlandet, Hamar Sykehus
  • Harstad, Norway
    • Universitetssykehuset i Nord-Norge, Harstad
  • Kristiansand, Norway
    • Sørlandet Sykehus HF, Kristiansand
  • Kristiansund, Norway
    • Helse Møre og Romsdal, Kristiansund Sjukehus
  • Levanger, Norway
    • Helse Nord Trøndelag, Levanger Sykehus
  • Lørenskog, Norway, 1478
    • Akershus Universitetssykehus, Lørenskog
  • Oslo, Norway
    • Oslo Universitetssykehus, Rikshospitalet
  • Oslo, Norway
    • Oslo universitetssykehus, Ullevål
  • Sandvika, Norway
    • Vestre Viken HF, Bærum Sykehus
  • Skien, Norway
    • Sykehuset Telemark, Skien
  • Stavanger, Norway
    • Stavanger Universitetssykehus
  • Tonsberg, Norway
    • Sykehuset Vestfold, Tønsberg
  • Volda, Norway
    • Helse Møre og Romsdal, Volda Sjukehus
  • Voss, Norway
    • Helse Bergen HF Voss Sjukehus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anti TNF discontinuation; Discontinuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)	Other: Discontinuation of anti-TNF treatment; Discontinuation of treatment with Infliximab, Adalimumab, and Golimumab in order to record time to relapse occurrences; Other Names: Remicade, Remsima, Inflectra, Humira, Simponi
Active Comparator: Anti TNF continuation; Continuation of anti-TNF treatment (Infliximab, Adalimumab, Golimumab)	Other: Continuation of anti-TNF treatment; Continuation of treatment with Infliximab, Adalimumab, and Golimumab for 2 years after randomization, then discontinue; Other Names: Remicade, Remsima, Inflectra, Humira, Simponi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in sustained clinical remission	Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 2 years of randomized treatment	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients in sustained clinical remission	Remission confirmed endoscopically by mucosal healing defined as Mayo Endoscopic Subscore (MES) score 0 or 1 after 4 years of randomized treatment	4 years
Time from randomization to relapse	Relapse time	2 years
Time from randomization to relapse	Relapse time	4 years
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy	Remission, but no need to restart anti-tnf therapy	2 years
Proportion of patients who are no longer in remission, but who do not need to restart anti-tumor necrosis factor (TNF) therapy	Remission, but no need to restart anti-tnf therapy	4 years
Proportion of relapse patients achieving remission after anti-TNF restart	Remission after relapse	2 years
Proportion of relapse patients achieving remission after anti-TNF restart	Remission after relapse	4 years
Adverse events and serious adverse events frequency and severity	Adverse events	2 years
Adverse events and serious adverse events frequency and severity	Adverse events	4 years

Collaborators and Investigators

• Sponsor: Helse Møre og Romsdal HF
• Collaborators: University of Oslo; Oslo University Hospital
• Investigators: Study Director: Dag Arne L Hoff, md, phd, Helse Møre og Romsdal Hospital Trust

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2017
• Primary Completion (Actual): January 20, 2025
• Study Completion (Actual): January 20, 2025

Study Registration Dates

• First Submitted: January 2, 2017
• First Submitted That Met QC Criteria: January 3, 2017
• First Posted (Estimated): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 31, 2025
• Last Update Submitted That Met QC Criteria: May 27, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Recurrence; Golimumab; Infliximab; Adalimumab; Tumor Necrosis Factor-alpha/antagonists & inhibitors
• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Necrosis; Colitis; Colitis, Ulcerative; Ulcer; Tumor Necrosis Factor Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Inflammatory Agents; Gastrointestinal Agents; Antirheumatic Agents; Dermatologic Agents; Adalimumab; Infliximab; Antibodies, Monoclonal; Golimumab
• Other Study ID Numbers: HMR2016-0.6; 2016-001409-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At this time there is no such plan for IPD sharing. It might be an issue regarding material stored in the study Biobank - that will be elucidated at a later stage.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No