EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis — EFFICACI  

Ulcerative Colitis Clinical Trial

Official title: EFFICACI : EFFicacy of Intravenous Infliximab Versus Vedolizumab After Failure of subCutaneous Anti-TNF in Patients With UlCerative Colitis : A Double Blinded Randomized Clinical Trial

Status Recruiting

Clinical Trial Summary

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that results from immune dysregulation. Arguably, the development of Tumor Necrosis Factor (TNF) antagonists (including infliximab, adalimumab and golimumab) revolutionized the management of immune-mediated chronic diseases in the past two decades.

However, about one third of patients will not respond to a first anti-TNF treatment and 10% to 30% will loose response to anti-TNF during the follow-up.

Historically, a switch between anti-TNF was performed to recapture remission and response to anti-TNF. Recently, a new biologic therapy blocking another target has been approved and is now reimbursed during ulcerative colitis, namely vedolizumab. Vedolizumab is an anti-integrin agent avoiding the recruitment of lymphocytes specifically in inflamed gut tissue.

Emerging data suggest that a switch of therapeutic class (meaning a change of biologic target with Non-TNF-targeted biologic) in case of clinical failure or insufficient response to anti-TNF may be the best choice. This idea of a switch out of the anti-TNF class is also supported by data on drug monitoring that may help physician decision making in case of loss of response. However, no trial is currently available and ongoing to assess the best therapeutic strategy. The aim of the proposed study is to assess the best biological based strategy in patient losing response to a first subcutaneous anti-TNF (golimumab and/or adalimumab).

Clinical Trial Description

Design :

A prospective, multicenter, randomized, double blind clinical trial

Primary objective :

To determine whether a non-TNF-targeted biologic (vedolizumab) is superior to infliximab to treat patient with UC losing response or with a primary failure to a first subcutaneous anti-TNF drug at week 14.

Secondary objective :

• To assess the rate of clinical response and remission at Week 54 in each group of treatments and the time to clinical response and remission from baseline ;

• To assess the changes in faecal calprotectin levels from baseline to week 14 and 54 according to treatment ;

• To assess the rate of colectomy and hospitalization in each treatment group ;

• To assess the rate of mucosal healing at week 14 and 54 in each group of treatments ;

• To assess the rate of loss of response in each group of treatments for patients responder after induction phase ;

• To assess the changes of quality of life indexes and the disability index from baseline to week 14 and 54 ;

• To determine the safety profile of each group of treatments ;

• To characterize the response in each group of treatments according to drug monitoring of the first anti-TNF agent ;

• To describe the pharmacokinetics of infliximab and vedolizumab as second-line treatment of UC and explore the sources of pharmacokinetic inter-individual variability ;

• To identify predictive factors of response to the treatment, including pharmacokinetic features

Expected findings and impact:

The patients include in the clinical will not lose any benefit since both treatments are actually indicated and effective in this condition. In both arm of treatment, patients will receive an effective treatment.

The study will optimize physician decision making to decrease the disease activity period in UC patients with known consequence such as hospitalisation, surgery, work cessations with related cost effects. ;

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

• NCT number: NCT03679546
• Study type: Interventional
• Source: Rennes University Hospital
• Contact: Guillaume BOUGUEN, MD
• Phone: 0299284321
• Email: guillaume.bouguen@chu-rennes.fr
• Status: Recruiting
• Phase: Phase 4
• Start date: January 4, 2019
• Completion date: January 4, 2025