Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used. However recent data suggests that chromoendoscopy is a better method of surveillance. Using 5-aminosalicylic acid agents primarily for chemoprevention is an ongoing debate however, when prescribed along with other strategies to control inflammation, their use is considered of benefit. This review presents current understanding of risk factors of neoplasia focusing on dysplasia and preventive strategies. Areas covered: PubMed search was done using key words to assess current evidence. Along with genetics, risk factors, strategies that modify the risk of dysplasia, and CRC in IBD are discussed in detail. Expert commentary: The role of our strategies in modifying CRC risk needs further assessment. Future research should aim to fill knowledge gaps such as high quality evidence for Chromoendoscopy and development of molecular markers for dysplasia detection. Our ultimate goal would be to eliminate CRC and is possible by better understanding of key pathogenic mechanisms in IBD.

BACKGROUND Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed ( P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

Vedolizumab is a monoclonal antibody that selectively inhibits the migration of α4-β7 positive inflammatory cells to the gastrointestinal tract. In the GEMINI 1 randomized double-blinded placebo-controlled trial of vedolizumab in ulcerative colitis (UC), the response rate was 47.1% at week six and, for patients receiving vedolizumab every 8 weeks, 56.6% at week 52. Of interest, however, is that despite a clinical remission rate of 16.9% at week six there was a mucosal healing rate of 40.9% at the same time point. Again, after 52 weeks of treatment, 41.8% of patients were in clinical remission, but 51.6% had complete mucosal healing. These findings suggest that symptoms of post-inflammatory irritability of the bowel may reduce the perceived clinical response rates. 1 In the GEMINI 2 randomized double-blind placebo-controlled trial of vedolizumab in Crohn's disease (CD), the remission rate was 14.5% at week six and 39% at week 52 with 8-weekly vedolizumab treatment. 2 Since the pivotal Phase III studies, there have been several publications from various centers that have collected real-life data for the management of UC and CD with vedolizumab. A systematic pooled analysis of nine studies that included 1565 (571 UC and 994 CD) adult patients with inflammatory bowel disease identified that in CD, vedolizumab achieved a 54% clinical response and 22% remission at week six and 49% responded and 32% were in remission by week 14. This was similar to the findings at week 52 where 45% of patients were responding and 32% were in clinical remission. In UC, vedolizumab achieved a 43% clinical response and 25% remission at week six and 51% responded and 30% were in remission by week 14. This was similar to the findings at week 52 where 48% of patients were responding and 39% were in clinical remission. 3 What appear to be better findings, however, were seen in a retrospective study of 27 centers from Finland that included 247 patients (139 UC and 108 CD), in which clinical remission was achieved at 6 months in 42% of treatment persistent patients with CD and 73% of treatment persistent patients with UC. 4 More recently, there have been numerous abstracts presented from many countries around the world. From the Netherlands, endoscopic response to vedolizumab therapy was observed in 8/15 (47%) patients with CD and 9/11 (82%) patients with UC, but the clinical remission rates were < 50% in both CD and UC. 5 In Scotland, 340 patients (203 CD and 137 UC) experienced lower hospitalization rates and steroid usage associated with vedolizumab treatment. 6 In Spain, a study of 274 patients (144 CD and 130 UC) identified that vedolizumab was more likely to be effective in UC than CD, if the patients were anti-tumor necrosis factor naïve and if they had mild or moderate disease, instead of severe disease. 7 In Ireland, a study of 39 UC patients treated with vedolizumab resulted in clinical response rates of 47% at 3 months and 46% at 6 months. 8 In Canada, endoscopic remission was 41% at 6 months and 48% at 12 months in UC, while clinical...

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