Editorial: treating strictures in inflammatory bowel disease

Intestinal strictures occur in up to 50% of patients with Crohn's disease. De novo1 and anastomotic strictures2 arise at sites of deep ulcers.

The thickened bowel wall consists of smooth muscle hypertrophy together with fibrosis, inflammation, and mucosal ulcers.3 De novo4 and anastomotic strictures5 may be associated with particular microbial “signatures.”

Stricture management has focussed on endoscopic balloon dilation and surgical strictureplasty or resection. Balloon dilation provides prolonged benefit in most patients.6 Surgical strictureplasty relieves obstruction while limiting bowel resection.7 Little attention has been given to drug therapy due to the belief that strictures are fibrotic and irreversible. In early studies of biologic drugs in Crohn's disease, some patients with strictures developed intestinal obstruction, related to scarring associated with rapid healing. In subsequent drug studies, patients with known strictures were excluded.

Drug therapy has an underestimated role in stricture treatment. In a prospective, uncontrolled, cohort study, two-thirds of 97 Crohn's disease patients with symptomatic small bowel strictures responded to treatment with adalimumab.8 Half the patients avoided a resection at 4 years.

In the article by Rieder et al9, expert gastroenterologists and radiologists have undertaken a systematic review and consensus voting to establish a stricture definition, define optimal diagnostic tools, and establish clinical trial parameters for drug studies. They considered magnetic resonance imaging (MRI), the optimal modality for stricture definition and monitoring the response to treatment. They defined fibrotic strictures as combined luminal narrowing, wall thickening, and pre-stenotic dilation. These criteria would capture patients with severe strictures, but exclude patients without, or with intermittent, dilation. An inability to pass a stricture with a known diameter endoscope may be a more objective measure of severity and response to treatment, although its use would be limited to colonic, anastomotic, and accessible small bowel strictures.

In the study by Bouhnik et al, the primary endpoint comprised obstructive symptom relief with the avoidance of corticosteroids, balloon dilation, and surgery at week 24 of treatment.8 Rieder et al defined the need for intervention (endoscopic balloon dilation or surgery) within 24-48 weeks as the most appropriate primary endpoint for drug studies.9 A primary endpoint that includes symptom relief may be more sensitive to change with therapy.

Some investigative tools and clinical scenarios remain unexplored. Abdominal ultrasound defines bowel morphology and inflammation well, and is inexpensive and non-invasive. Markers of inflammation, CRP, and faecal calprotectin, are not only of proven value in the management of luminal disease10 but may also be useful to measure treatment response. Large bowel strictures, and strictures occurring in ulcerative colitis, need to be studied and managed.

Therapeutic studies of anti-inflammatory and anti-fibrotic drugs are needed to establish best stricture management. Studies may require endoscopic dilation to relieve mechanical obstruction together with drug therapy to alter the pathological process. Stricture definitions, characterisation, measures of change with treatment, and study endpoints require clinical validation. Improved treatment of this serious complication of inflammatory bowel disease is overdue.

FUNDING INFORMATION

Michael Kamm has received research funding from AbbVie, the Helmsley Charitable Trust, and the Spotlight Foundation. No funding was received for this editorial.