Emerging challenges in inflammatory bowel disease

Background: Emerging challenges in inflammatory bowel disease (IBD) include a dramatic rise in the disease burden of developing nations as well as an increase in complex disease behaviour. In order to meet these challenges, greater global understanding of IBD epidemiology is required, as well as the development of efficient strategies to manage complex disease phenotypes. A paucity of collective information about IBD in South America exists within the literature. Furthermore, the combination of endoscopic balloon dilation (EBD) and ustekinumab, a relatively new biological agent, has never been evaluated for the treatment of stricturing Crohn’s disease (CD). The work incorporated in this thesis aims to address these issues. Methods: Two studies were undertaken. A systematic review was conducted to report the epidemiology and disease characteristics of IBD within the South American continent. A retrospective cohort study was performed to evaluate the efficacy and safety of EBD with or without ustekinumab biological therapy for the treatment of stricturing CD. Results: Ulcerative colitis (UC) is more prevalent than CD within the South American continent (15.0-24.1 versus 2.4-14.1 per 100,000 individuals). The incidence and prevalence of both UC and CD has dramatically risen in Brazil, Colombia and Uruguay. IBD was more common in urban centres whilst colonic CD and pancolonic UC represented the most commonly reported IBD phenotypes. Stricture resolution was significantly more likely in patients who received EBD with ustekinumab compared to EBD with non-ustekinumab biological agents (OR 6.60; 95% CI 1.45-34.05; p < 0.01), EBD with no-biological agent (OR 6.89; 95% CI 1.36-30.97, p = 0.01), or EBD and not-on ustekinumab therapy (OR 6.88; 95% CI 1.68-31.74; p < 0.01). Long-term success, defined as surgery-free survival for one year after EBD, was achieved in 100% (95% CI 76-100) of patients who received EBD with ustekinumab. None of the patients in this study required rescue surgical intervention for procedure-related complications. Conclusion: The IBD burden in South America is rapidly rising, thus mirroring the epidemiological shift seen in other developing nations. EBD with ustekinumab is a safe and effective therapeutic strategy for the management of stricturing CD. These findings help bridge current knowledge gaps and enhance our collective effort to address the emerging challenges in IBD.