Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. Dec 16, 2020; 12(12): 542-554
Published online Dec 16, 2020. doi: 10.4253/wjge.v12.i12.542
Crohn’s strictures open with anti-mycobacterial antibiotic therapy: A retrospective review
Rhys Collyer, Annabel Clancy, Gaurav Agrawal, Thomas J Borody
Rhys Collyer, Annabel Clancy, Gaurav Agrawal, Thomas J Borody, Centre for Digestive Diseases, Five Dock 2046, NSW, Australia
Author contributions: All authors contributed to conceptualization, investigation and validation; Collyer R and Clancy A performed data curation and formal analysis; Clancy A, Agrawal G and Borody TJ contributed to project administration and provided supervision; Agrawal G and Borody TJ contributed to resources; Collyer R performed visualization; all authors wrote the original draft, reviewed and edited the manuscript, and issued the final approval of the submitted version.
Institutional review board statement: The study was reviewed and approved by the Institutional Ethics Committee (STUDY NO. CDD19/C01) at Centre for Digestive Diseases, NSW, Australia.
Informed consent statement: A waiver of consent was granted for this study. Patients were not required to give informed consent for this study because the analysis used de-identified data that was obtained after each patient consented to the treatment.
Conflict-of-interest statement: Dr. Borody TJ reports personal fees from THE CENTRE FOR DIGESTIVE DISEASES, other from OTAKARO PATHWAY, other from FINCH THERAPEUTICS, other from REDHILL BIO, outside the submitted work; in addition, Dr. Borody TJ has a patent US16/233419 pending, a patent AU2018256633A1 pending, a patent WO2011050397A1 pending, a patent US20180344782A1 pending, a patent CA3003138A1 issued, a patent AU2011286165 issued, a patent AU20111286165B2 issued, a patent US9308226 issued, a patent US9198926 licensed, a patent US9072763 licensed, and a patent AU2010903474 issued.
Data sharing statement: All data relevant to the study are included in this article.
STROBE statement: The authors have read the STROBE Statement – checklist of items, and the manuscript was prepared and revised according to the STROBE Statement – checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Thomas J Borody, AGAF, BSc, DSc, FACG, FACP, FRACP, MBBS, MD, PhD, Professor, Centre for Digestive Diseases, Level 1, 229 Great North Road, Five Dock 2046, NSW, Australia. thomas.borody@cdd.com.au
Received: October 2, 2020
Peer-review started: October 2, 2020
First decision: October 17, 2020
Revised: November 2, 2020
Accepted: November 17, 2020
Article in press: November 17, 2020
Published online: December 16, 2020
Abstract
BACKGROUND

Medical therapy for strictures is limited and first-line treatment consists of endoscopic balloon dilatation, strictureplasty or surgical resection. Mycobacterium tuberculosis, Helicobacter pylori and Streptococcus can all cause stenosis, for which antibiotic treatment achieves stricture resolution. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in Crohn’s disease (CD). Thus, specialized antimicrobial treatment, in particular, anti-mycobacterial antibiotic therapy (AMAT) has been proposed as a potential treatment option. To our knowledge, the opening of CD strictures has not been recorded using any form of antibiotic therapy. We hypothesized that AMAT would resolve strictures in patients with CD.

AIM

To investigate the effect and outcomes of AMAT in a cohort of CD patients with an ileal stricture.

METHODS

A single center, retrospective, medical record case review was conducted on an observational cohort of patients with CD who had an ileal stricture on colonoscopy and were treated with AMAT. Forty patients meeting the inclusion criteria were identified from the internal medical database. Thirty (75%) patients had follow-up colonoscopy and clinical data available. The AMAT regimen was prescribed after the initial colonoscopy for a duration of at least six months until follow-up colonoscopy with the attending gastroenterologist. Patient demographics, symptoms, colonoscopy reports, inflammatory serum markers and concurrent medications were recorded at pre-treatment and follow-up between January 1995 and June 2018.

RESULTS

Of the patients that returned for follow-up after > 24 mo of AMAT, twenty (67%) had complete resolution (CR) of their ileal strictures, three (10%) had partial resolution and seven (23%) had no resolution. Irrespective of stricture outcome, 21 patients (70%) demonstrated clinical response to AMAT and there was a statistically significant reduction in inflammatory serum markers C-reactive protein (P < 0.0001) and erythrocyte sedimentation rate (P = 0.04) from pre-treatment to follow-up. It was observed that 11 (37%) patients experienced side effects, but no serious adverse effects were attributable to AMAT. At follow-up there were 26 (87%) patients on concomitant medication for CD and a statistically significant association between CR and AMAT with a concomitant immunomodulator (P = 0.02).

CONCLUSION

This study demonstrated a high rate of stricture resolution (67%) similar to that seen in tuberculosis strictures (70%), suggesting a shared mycobacterial origin of strictures, and perhaps disease.

Keywords: Antibiotics, Colonoscopy, Crohn’s disease, Ileum, Inflammatory bowel disease, Stricture

Core Tip: Crohn’s disease (CD) is a chronic, incurable inflammatory bowel disease rising in incidence and prevalence. Strictures are a significant complication of CD with current first-line treatments including dilatation and/or surgery. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in CD and the proposed treatment is anti-mycobacterial antibiotic therapy (AMAT). Preliminary results indicate AMAT for atypical Mycobacteria opens CD strictures efficaciously and reliably. Our study provides an alternative to endoscopic and surgical intervention to treat strictures in CD. Our findings should be validated by further randomized controlled trials.