De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease

NCT04646187 | Enrolling By Invitation Phase 4 DMC

• 2 other identifiers: 2020002612020-001811-26
• Study Type: interventional
• Target: 148
• Locations: 3 countries
• Sites: 7

Brief Summary

BACKGROUND/RATIONALE: Treatment outcomes of patients with inflammatory bowel disease (IBD) have improved enormously during the past decade due to the use of anti-tumour necrosis factor (anti-TNF) therapy. As a result, 67 to 91% of paediatric patients and 66% of adult patients is still in sustained remission two years after the initiation of anti-TNF therapy. Prolonged use of anti-TNFs comes with disadvantages such as dose dependent susceptibility to infections and dermatological adverse effects. Preliminary, mostly uncontrolled studies suggest that dose reduction by dosing interval lengthening is a realistic option in a relevant proportion of patients with IBD, provided that intensive follow-up is applied. OBJECTIVE: To evaluate whether a faecal calprotectin (FC) guided strategy of anti-TNF dosing interval lengthening is non-inferior in maintaining remission in patients with IBD, compared with an unchanged dosing interval.

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Keywords

Infliximab; Adalimumab; Tumor Necrosis Factor-alpha; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Outcome Measures

Primary Outcomes (1)

• cumulative incidence of out-of-range fecal calprotectin results at 48 weeks follow-up

  Out-of-range FC results are defined as fecal calprotectin above the target range (i.e. \>250 μg/g for CD patients; \>150 μg/g for UC patients) and at least 100 μg/g increase compared with the previous result, unless the previous result was already above the target range.

  48 weeks

Secondary Outcomes (5)

• Time to get out-of-range fecal calprotectin results

  up to 48 weeks

• Cumulative incidence of anti-TNF-associated respiratory infections and dermatological adverse effects at 48 weeks follow-up

  48 weeks

• Evolution of FC and anti-TNF trough levels in the first 16 weeks after reverting to previous dosing interval

  Up to 48+16 weeks

• Proportion of patients developing loss-of-response in the first 16 weeks after reverting to the previous dosing interval

  Up to 48+16 weeks

• Identification of predictors of successful de-escalation.

  48 weeks

Other Outcomes (1)

• Patients' attitudes towards deprescribing anti-TNF agents

  48 weeks

Study Arms (2)

Intervention group

EXPERIMENTAL

In patients treated with adalimumab, the dosing interval will be lengthened from 2 to 3 weeks. In patients treated with infliximab, the dosing interval will be lengthened from 8 to 12 weeks. Consists of two groups: Patients randomised to the intervention group and patients allocated to the intervention group based on preference.

Biological: Infliximab; Biological: Adalimumab

Control group

NO INTERVENTION

Unchanged dosing interval. Consists of two groups: Patients randomised to the control group and patients allocated to the control group based on preference.

Interventions

Infliximab BIOLOGICAL

Dosing interval lengthening from 8 to 12 weeks

Also known as: Remicade, Flixabi, Inflectra, Remsima, Zessly

Intervention group

Adalimumab BIOLOGICAL

Dosing interval lengthening from 2 to 3 weeks

Also known as: Humira, AMGEVITA, Hulio, Hyrimoz, Idacio, Imraldi

Intervention group

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged 12-25 years
• Diagnosed with luminal Crohn's disease or ulcerative colitis
• Treated with either 8-weekly infliximab or 2-weekly adalimumab
• Current anti-TNF agent as first ever anti-TNF agent or prior anti-TNF agent discontinued for reason other than primary non-response or secondary loss-of-response
• No previous attempts to lengthen the dosing interval
• Three consecutive faecal calprotectin (FC) results in the target range (i.e. \<250 μg/g for CD patients; \<150 μg/g for UC patients) in the previous 6 months or confirmed endoscopic remission within 2 months before study entry (i.e. simple endoscopic score for Crohn's disease (SES-CD) \<3 points for CD patients; ulcerative colitis endoscopic index of severity (UCEIS) ≤1 point for UC patients)
• Absence of symptoms associated with active IBD (judged by the local IBD-team)
• Written informed consent granted

You may not qualify if:

• Perianal fistula
• Presence of ileostomy or ileoanal pouch (as FC cut-off is not validated for small bowel faeces)
• Any inflammatory comorbidity, such as rheumatoid arthritis
• Current treatment with corticosteroids (prednisone or budesonide)
• Current pregnancy

Sponsors & Collaborators

• University Medical Center Groningen: lead
• European Crohn´s and Colitis Organisation: collaborator
• Bühlmann Laboratories AG: collaborator

Study Sites (7)

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Centre hospitalier universitaire de Liège

Liège, B-4000, Belgium

Location

Centre hospitalier régional de la Citadelle

Liège, Belgium

Location

Rijnstate Hospital

Arnhem, 6816 AD, Netherlands

Location

Catharina Hospital Eindhoven

Eindhoven, 5623 EJ, Netherlands

Location

University Medical Center Groningen

Groningen, 9700 RB, Netherlands

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, 08907, Spain

Location

Related Publications (1)

• Bouhuys M, Lexmond WS, Dijkstra G, Lobaton T, Louis E, van Biervliet S, Groen H, Guardiola J, Rheenen PV. Efficacy of anti-TNF dosing interval lengthening in adolescents and young adults with inflammatory bowel disease in sustained remission (FREE-study): protocol for a partially randomised patient preference trial. BMJ Open. 2021 Nov 3;11(11):e054154. doi: 10.1136/bmjopen-2021-054154.

  PMID: 34732500 DERIVED

MeSH Terms

Conditions

Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative

Interventions

Infliximab; CT-P13; Adalimumab

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Colitis; Colonic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Humanized

Study Officials

• Patrick F van Rheenen, MD PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: November 20, 2020
• First Posted: November 27, 2020
• Study Start: March 11, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: January 6, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); BE (3); NL (3)