Medicine (St Vincent's) - Theses
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ItemDefining and Treating Crohn's Disease Strictures( 2021)Crohn’s disease, one of two main Inflammatory Bowel Diseases (IBD), is a relapsing and remitting inflammatory condition of the digestive tract leading to progressive and cumulative damage to the gastrointestinal tract. Strictures are the most common complication of Crohn's disease. Already at diagnosis between 11% and 30% of patients have stricturing disease and 1 in 3 will develop stricturing after five years, with many requiring bowel surgery. Previously, strictures have been regarded as a contraindication for drug therapy, based on the premise that such strictures comprise irreversible fibrosis. Treatment has been endoscopic dilation or surgery. Pathways leading to fibrosis are now more comprehensively understood and the important contribution of both acute and chronic inflammation as well as smooth muscle hyperplasia/hypertrophy are increasingly recognized as key factors in stricture pathogenesis. This thesis investigates, in a range of studies, the diagnostic, prognostic and non-surgical treatment modalities for patients with stricturing Crohn’s disease. I have comprehensively reviewed the current evidence for drug therapy in Crohn’s disease and highlighted the limited current data supporting drug treatment in the management of strictures. In addition, I have outlined the current position for endoscopic therapy, particularly endoscopic balloon dilation as part of the management of strictures. I have evaluated the key demographic, clinical, endoscopic and imaging risk factors for progression to surgery. The key role of MRI small bowel for detailed evaluation of patients with stricturing Crohn’s and its utility to predict stricture surgery has been defined. The Stricture Definition and Treatment (STRIDENT) study is the first randomised controlled study of drug treatment in stricturing Crohn’s disease. As part of this study, I have demonstrated the outcomes of drug therapy, including intensive drug treatment with treat to target dosing of adalimumab in combination with a thiopurine, and treatment with standard dosing anti-TNF monotherapy. In addition to clinical outcomes, this study prospectively and objectively demonstrates the morphological stricture changes associated with treatment using multiple imaging modalities (MRI, intestinal ultrasound, and endoscopy) and the effect on biomarkers of inflammation (CRP, faecal calprotectin). This research has demonstrated that Crohn’s disease strictures are responsive to drug therapy and that tighter control from intensive treatment results in less treatment failure and greater improvement in stricture morphology. These series of studies on the diagnosis and treatment of patients with stricturing Crohn’s disease will help change the current treatment paradigm for this disabling condition. Future scientific studies will provide further insights into the pathophysiology of strictures to further improve patient outcomes.