Prevention and Treatment of Stricturing Crohn’s Disease – Perspectives and Challenges

ABSTRACT

Introduction: Fibrostenosis is a hallmark of Crohn’s disease (CD), remains a challenge in today’s clinical management of inflammatory bowel disease patients and represents a key event in the disease course necessitating improved preventative strategies and a multidisciplinary approach to diagnosis and management. With the advent of anti-fibrotic therapies and well-defined clinical endpoints for stricturing CD, there is promise to impact the natural history of disease.

Areas covered: This review summarizes current evidence in the natural history of stricturing Crohn’s disease, discusses management approaches as well as future perspectives on intestinal fibrosis.

Expert opinion: Currently, there are no specific therapies to prevent progression to fibrosis or to treat it after it becomes clinically apparent. In addition to the international effort by the Stenosis Therapy and Anti-Fibrotic Research (STAR) consortium to standardize definitions and propose endpoints in the management of stricturing CD, further research to improve our understanding of mechanisms of intestinal fibrosis will help pave the way for the development of future anti-fibrotic therapies.

KEYWORDS:

• Anti-fibrotic
• stricture
• stenosis
• fibrosis
• enterography
• endoscopic balloon dilation
• strictureplasty
• surgery
• inflammatory bowel disease
• Crohn’s disease

Disclosure statement

F Rieder is on the advisory board or consultant for Agomab, Allergan, AbbVie, Boehringer-Ingelheim, Celgene, CDISC, Cowen, Genentech, Gilead, Gossamer, Guidepoint, Helmsley, Index Pharma, Janssen, Koutif, Metacrine, Morphic, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Takeda, Techlab, Theravance, Thetis, UCB. B L Cohen receives the following financial support: advisory boards and consultant for Abbvie, Celgene-Bristol Myers Squibb, Pfizer, Sublimity Therapeutics, TARGET RWE; CME Companies: Cornerstones, Vindico; speaking: Abbvie. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article Highlights

• More than half of patients with Crohn’s disease (CD) develop clinically apparent strictures with subsequent intestinal obstruction or penetrating disease. This has remained largely unchanged despite advances in medical therapy

• Both inflammation-dependent and inflammation-independent mechanisms may drive fibrogenesis in CD

• A stricture is defined radiologically by the presence of at least 2 out of the 3 following criteria: localized luminal narrowing (>50% luminal narrowing), bowel wall thickening and pre-stenotic dilation (generally > 3 cm in diameter).

• Endoscopic balloon dilation is an option for short, non-angulated strictures which are accessible endoscopically and not associated with penetrating disease or malignancy

• Bowel resection and strictureplasty are the mainstays of surgical treatment of stricturing disease

• Colon strictures deserve special attention given an increased risk of dysplasia compared with small bowel strictures. Earlier referral to surgery should be considered

Additional information

Funding

This paper was supported by the Helmsley Charitable Trust through the Stenosis Therapy and Anti-Fibrotic Research consortium (STAR) National Institutes of Health [K08DK110415 & R01DK123233] to F.Rieder.