A randomized controlled trial of antibiotics targeting adherent and invasive Escherichia coli versus placebo in Crohn's disease: the TEOREM trial

Abstract

Background: A subset of patients with ileal Crohn's disease (CD) are colonized with adherent-invasive Escherichia coli (AIEC).

Objective: This prospective trial tested the efficacy of antibiotics for endoscopic response in CD patients colonized with AIEC.

Design: Patients with endoscopically active, ileal CD, colonized with AIEC, were randomized to receive oral ciprofloxacin and rifaximin or double placebo for 12 weeks. AIEC was detected in ileal biopsies, by phenotypic analysis. The primary endpoint was endoscopic overall response, as defined by a CD endoscopic index of severity adapted to patients with ileal CD. Central readers blinded to the treatment scored video recordings of colonoscopies at preinclusion and week 12. We expected a strong signal of efficacy for antibiotics in this subgroup of patients.

Results: Between May 2016 and June 2021, 155 patients were screened, and 24 patients were randomized, 12 in each arm. All patients' AIEC were sensitive to ciprofloxacin and rifaximin in vitro. There was no statistical difference between the 2 arms for endoscopic overall response (50% in the Cipro-Rifa group vs 33% in the placebo group, estimated difference 17%; 95% CI, -23% to 51%). Within the antibiotics arm, 7/10 patients became AIEC- and 3/10 patients remained AIEC+ (and acquired resistance to ciprofloxacin), as compared to 7/12 AIEC- and 5/12 AIEC+ in the placebo arm, respectively. There was no association between AIEC clearance and endoscopic endpoints.

Conclusions: A combination of ciprofloxacin and rifaximin was not superior to placebo to achieve endoscopic endpoints in patients with ileal CD colonized with AIEC.

Keywords: Crohn' disease; adherent-invasive Escherichia coli; antibiotics; ciprofloxacin; clinical trial; rifaximin.