Type of publication:
Conference abstract

Author(s):
Kumar A.; Quraishi M.N.; Al-Hassi H.O.; Elasrag M.; Segal J.P.; Jain M.; Steed H.; *Butterworth J.; Farmer A.; McLaughlin J.; Beggs A.; Brookes M.

Citation:
Journal of Crohn's and Colitis. Conference: 18th Congress of European Crohn's and Colitis Organisation, ECCO 2023. Copenhagen Denmark. 17(Supplement 1) (pp i532), 2023. Date of Publication: February 2023

Abstract:
Background: Surgery plays a pivotal role in ileal Crohn's disease despite the risk of endoscopic recurrence following an ileocaecal resection greater than 65% within 12 months of surgery. More than 90% of Crohn's patients have a concomitant diagnosis of bile acid diarrhoea following an ileal resection. This pilot study aimed to assess whether the use of bile acid sequestrants in post-operative Crohn's patients with bile acid diarrhoea can alter the microbiome and prevent disease recurrence. Method(s): Post-operative Crohn's patients with symptoms of diarrhoea underwent 75SeHCAT testing for bile acid diarrhoea. If positive (75SeHCAT < 15%), patients were treated with colesevelam and stool samples were collected at 4-weeks, 8-weeks and 6-12 months posttreatment. If negative (75SeHCAT > 15%), treatment was not given and were reviewed in clinic as per local guidelines. Patients underwent a 6-12 months post-operative colonoscopy where mucosal biopsies were taken. Disease activity was established using the endoscopic Rutgeert's score, with disease remission defined as Rutgeerts score < i2 and disease recurrence 3 i2. Faecal and mucosal 16S ribosomal RNA gene analysis was undertaken to assess a/b-diversity and microbial composition. Result(s): A total of 44 faecal samples and 44 mucosal biopsies were sequenced from 14 patients. 1/10 patients on colesevelam and 2/4 patients not on colesevelam demonstrated disease recurrence. There was no significant difference in a/b-diversity pre- and post-treatment. Pre-treatment, the three most abundant bacterial classes in all patients were Bacteroidia, Clostridia and Gammaproteobacteria (Figure 1). Following 6-12 months of treatment, out of the 9 patients on colesevelam, 5/9 (55.6%) had a reduction in Bacteroidia, 9/9 (100%) had an increase in Clostridia, and 7/9 (77.8%) had a reduction in Gammaproteobacteria. Of the two patients not given colesevelam, 1/2 (50%) showed a reduction in Bacteroidia, increase in Clostridia and a reduction in Gammaproteobacteria. Conclusion(s): This small pilot study demonstrated that patients who were given colesevelam, a bile acid sequestrant, were more likely to be in disease remission at their 6-12 months colonoscopy review. Furthermore, treatment with colesevelam may have a role in altering the microbiome to help maintain remission states in post-operative Crohn's disease. Larger mechanistic studies are now needed to confirm these findings and demonstrate statistical significance.

Link to full-text

Type of publication:
Randomised controlled trial

Author(s):
Rhodes J.M.; Subramanian S.; Martin K.; Probert C.; Flanagan P.K.; Horgan G.W.; Mansfield J.; Parkes M.; Hart A.; Dallal H.; Iqbal T.; *Butterworth J.; Culshaw K.

Citation:
Digestive Diseases and Sciences; Aug 2021; vol. 66 (no. 8); p. 2700-2711

Abstract:
Background: Increased mucosa-associated E. coli are present in Crohn's disease, but their role in pathogenesis is uncertain. Aim(s): To assess efficacy and safety of an antibiotic/hydroxychloroquine combination effective against E. coli inside macrophages. Method(s): Adults with moderately active disease (CDAI > 220-450 plus C reactive protein >= 5 mg/l and/or fecal calprotectin > 250 mug/g) were randomized to receive (open-label) oral budesonide (Entocort CR 9 mg/day 8 weeks, 6 mg/day 2 weeks, 3 mg/day 2 weeks) or oral ciprofloxacin 500 mg bd, doxycycline 100 mg bd, hydroxychloroquine 200 mg tds for 4 weeks, followed by doxycycline 100 mg bd and hydroxychloroquine 200 mg tds for 20 weeks. Primary endpoints were remission (CDAI <= 150) at 10 weeks, remission maintained to 24 weeks, and remission maintained to 52 weeks. Patients not responding (CDAI fall by > 70) by 10 weeks were invited to crossover onto the alternative therapy. Result(s): Fifty-nine patients were recruited across 8 sites. Including crossover, 39 patients received antibiotics/hydroxychloroquine and 39 received budesonide. At 10 weeks, 24 weeks, and 52 weeks on initial therapy, only 2/27, 2/27, and 1/27 were in remission on antibiotics/hydroxychloroquine compared with 8/32, 1/32, and 1/32 on budesonide (P = 0.092 at 10 weeks). Withdrawals by 10 weeks due to adverse events were seen in 15 receiving antibiotics/hydroxychloroquine and 6 budesonide. Results including crossover were more promising with 9/24 patients receiving antibiotics/hydroxychloroquine per protocol in remission by 24 weeks. No correlation was seen between response to antibiotics/hydroxychloroquine and ASCA/OmpC antibody status or disease location. Conclusion(s): Overall results with this antibiotic/hydroxychloroquine combination were unimpressive, but long-term remission is seen in some patients and justifies further study.

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