NCT04646187

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

De-escalation of Anti-TNF Therapy in Adolescents and Young Adults With IBD With Tight Faecal Calprotectin and Trough Level Monitoring

• Status: Enrolling By Invitation
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 148 (estimated)
• Sponsor: University Medical Center Groningen · Academic / Other
• Sex: All
• Age: 12 Years – 25 Years
• Healthy volunteers: Not accepted

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.

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.

Conditions

• Inflammatory Bowel Diseases
• Crohn Disease
• Colitis, Ulcerative

Interventions

Type	Name	Description
BIOLOGICAL	Infliximab	Dosing interval lengthening from 8 to 12 weeks
BIOLOGICAL	Adalimumab	Dosing interval lengthening from 2 to 3 weeks

Timeline

• Start date: 2021-03-11
• Primary completion: 2026-03-01
• Completion: 2026-03-01
• First posted: 2020-11-27
• Last updated: 2025-01-06

Locations

7 sites across 3 countries: Belgium, Netherlands, Spain