De-escalation of Anti-TNF Therapy in Inflammatory Bowel Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Infliximab, Adalimumab.
- Who it may be relevant to
- Registry conditions: Inflammatory Bowel Diseases, Crohn Disease, Colitis, Ulcerative. Basic parameters: 12 years — 25 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Belgium, Netherlands, Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
De-escalation of Anti-TNF Therapy in Adolescents and Young Adults With IBD With Tight Faecal Calprotectin and Trough Level Monitoring
Overview
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.
Detailed description
STUDY DESIGN:
International, multi-centre, prospective, partially randomised patient-preference trial.
STUDY POPULATION:
Study population: Eligible patients are aged 12-25 years with luminal Crohn's disease (CD) or ulcerative colitis (UC), who have three consecutive faecal calprotectin (FC) results in the target range (i.e. \<250 µg/g for CD patients; \<150 µg/g for UC patients) over a period of 6 months at study entry or recently confirmed endoscopic remission.
DE-ESCALATION STRATEGY:
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. FC rapid tests will be performed every 4 weeks and rapid tests for anti-TNF trough levels will be performed every 12 weeks.
MAIN STUDY ENDPOINTS:
The primary outcome is the cumulative incidence of out-of-range FC results at 48 weeks follow-up. Secondary endpoints include time to get out-of-range FC results, cumulative incidence of anti-TNF associated adverse effects, proportion of patients progressing from out-of-range FC to loss-of-response and identification of predictors of successful de-escalation.
ETHICAL CONSIDERATIONS:
Patients with reduced anti-TNF exposure may have a higher risk of out-of-range FC results and, on the other hand, may benefit from fewer hospital visits or injections and possibly a decrease in adverse effects of anti-TNF therapy. Tight monitoring of FC levels (i.e. 4-weekly) will allow institution of re-escalation before the patient manifests clinical signs of relapse. This study cannot be conducted without the participation of minors and young adults, who typically have a short disease duration. Early treatment with anti-TNF agents possibly modifies the course of their disease, which makes provision for safe deescalation.
Interventions
- Biological Infliximab
Dosing interval lengthening from 8 to 12 weeks - Biological Adalimumab
Dosing interval lengthening from 2 to 3 weeks
Primary outcome measures
- cumulative incidence of out-of-range fecal calprotectin results at 48 weeks follow-up [Time frame: 48 weeks]
Secondary outcome measures (5)
- Time to get out-of-range fecal calprotectin results [Time frame: up to 48 weeks]
- Cumulative incidence of anti-TNF-associated respiratory infections and dermatological adverse effects at 48 weeks follow-up [Time frame: 48 weeks]
- Evolution of FC and anti-TNF trough levels in the first 16 weeks after reverting to previous dosing interval [Time frame: Up to 48+16 weeks]
- Proportion of patients developing loss-of-response in the first 16 weeks after reverting to the previous dosing interval [Time frame: Up to 48+16 weeks]
- Identification of predictors of successful de-escalation. [Time frame: 48 weeks]
Eligibility criteria
Inclusion criteria
- 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
Exclusion criteria
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Belgium · 3 centers
- Universitair Ziekenhuis Gent — Ghent
- Centre hospitalier universitaire de Liège — Liège
- Centre hospitalier régional de la Citadelle — Liège
Netherlands · 3 centers
- Rijnstate Hospital — Arnhem
- Catharina Hospital Eindhoven — Eindhoven
- University Medical Center Groningen — Groningen
Spain · 1 center
- Hospital Universitari de Bellvitge — L'Hospitalet de Llobregat
Publications
- Bouhuys M, Wessels MMS, de Vries W, Lambeck AJA, Touw DJ, van Rheenen PF. Lateral flow test versus enzyme-linked immunosorbent assay to measure infliximab trough concentrations: A head-to-head comparison. J Pediatr Gastroenterol Nutr. 2024 Dec;79(6):1134-1141. doi: 10.1002/jpn3.12372. Epub 2024 Oct 10. PMID 39390697
- 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
Identifiers
NCT: NCT04646187 · 202000261 · 2020-001811-26