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

Crohn Disease Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Crohn Disease
• Inflammatory Bowel Diseases
• Intestinal Diseases

• NCT number: NCT04646187
• Study type: Interventional
• Source: University Medical Center Groningen
• Status: Enrolling by invitation
• Phase: Phase 4
• Start date: March 11, 2021
• Completion date: March 2025