IBD: What's new in 2015: Professor Laurent Peyrin-Biroulet (Nancy, France), Professor Prateek Sharma (Kansas, USA), Professor Brian Feagan (London, Canada) and Professor David Wilson (Edinburgh, UK) discuss their highlights of UEGW 2015. Conducted by Sanjay Tanday.

by Sanjay Tanday: Advances in diagnostics and therapy means the prospects of living a normal active life free of symptoms and disability are better than ever for IBD patients. The most important new developments for 2015 were summarised in an educational symposium at UEGW 2015.
Monitoring for endoscopic healing and signs of disease progression is an essential part of IBD care. Dr Edouard Louis from Liege in Belgium pointed out that although the therapeutic target in IBD remains insufficiently defined, implementation of better tools for monitoring inflammatory markers, drug levels and morphological assessments may improve short- and long-term outcomes. Faecal calprotectin levels remain an important surrogate marker of mucosal healing and have been shown to correlate with disease activity¹ and to predict remission during treatment with infliximab² and following surgery.³ Monitoring of faecal calprotectin levels may be combined with other biomarkers such as hepatocyte growth factor (HGF) and vascular cell adhesion molecule 1 (VCAM-1) for greater predictive power.⁴ A test kit for self-monitoring of faecal calprotectin levels at home via a smartphone app will make it easier for patients to self-manage their condition.
Dr Ingrid Ordas, gastroenterologist from Barcelona, and professor of radiology Andrea Laghi from Rome reviewed the latest in the field of imaging. Magnetic resonance (MR) enterography is a sensitive and reliable method of evaluating mucosal healing and therapeutic response.⁵ Diffusion-weighted MR imaging is a quick and easy method that does not require administration of intravenous contrast or bowel preparation; however, the image quality is low and the high rate of false positives means there is a risk of overtreatment.⁶ Detecting fibrosis and discriminating it from inflamed tissue is an important task in IBD; ultrasonography (US)-based elastography is a non-invasive method for evaluating tissue hardness by detecting increased collagen content in gut tissue and has been shown to differentiate between affected and unaffected segments before and after surgery in CD patients.^{7, 8} Future developments in imaging are likely to include PET scanning with a fluorodeoxyglucose (FDG) tracer to evaluate fibrosis,⁹ and cell labelling of activated macrophages for monitoring inflammation.
Last but not least, new developments in therapy were reviewed by Professor Matthieu Allez from Paris who predicted that early combined immunosuppressive treatment will play an increasingly important role following the results of the REACT trial, which showed that although early combined immunosuppression was no more effective than conventional management for treating CD symptoms, the rate of major adverse outcomes was significantly lower in the former group.¹⁰ Another study that confirms the importance of taking early action in high-risk patients is the POCER trial which showed that adalimumab was superior to thiopurines for preventing endoscopic recurrence for up to 18 months post-surgery.¹¹ Professor Matthieu also mentioned the UNITI study programme which evaluates ustekinumab, a monoclonal antibody against IL-12/23, in anti-TNF-refractory CD and shows superior clinical response rates compared with placebo in this setting. Amongst new therapies, the development of anti-adhesion therapies continues beyond vedolizumab: the TURANDOT study showed that the anti-MAdCAM antibody PF-00547659 was superior to placebo for inducing clinical remission and mucosal healing in patients with moderate to severe UC.¹² Small molecules that are being developed to target new pathways include ozanimod, a selective sphingosine 1-phosphate 1 receptor (S1P1R) modulator which was shown to be effective for inducing remission, clinical response and mucosal improvement for up to 32 weeks in moderate to severe UC,^{13, 14} and the oral SMAD7 antisense oligonucleotide mongersen which has demonstrated superior clinical efficacy and safety over placebo in moderate to severe CD.¹⁵
References
 

1. D’Haens G, Ferrante M, Vermeire S, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218-24.
2.  De Vos M, Dewit O, D’Haens G, et al. Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naive patients with ulcerative colitis. J Crohns Colitis 2012;6:557-62.
3. Wright EK, Kamm MA, De Cruz P, et al. Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn’s disease after surgery. Gastroenterology 2015;148:938-947 e1.
4. de Bruyn M, Bessissow T, Billiet T, et al. DOP063 Biomarker panel for prediction of mucosal healing in patients with Crohn’s disease under infliximab therapy. Journal of Crohn’s and Colitis 2014;8, Supplement 1:S45-S46.
5. Ordas I, Rimola J, Rodriguez S, et al. Accuracy of magnetic resonance enterography in assessing response to therapy and mucosal healing in patients with Crohn’s disease. Gastroenterology 2014;146:374-82 e1.
6. Choi SH, Kim KW, Lee JY, et al. Diffusion-weighted Magnetic Resonance Enterography for Evaluating Bowel Inflammation in Crohn’s Disease: A Systematic Review and Meta-analysis. Inflammatory Bowel Diseases 9000;Publish Ahead of Print.
7. Stidham RW, Xu J, Johnson LA, et al. Ultrasound elasticity imaging for detecting intestinal fibrosis and inflammation in rats and humans with Crohn’s disease. Gastroenterology 2011;141:819-826 e1.
8. Baumgart DC, Muller HP, Grittner U, et al. US-based Real-time Elastography for the Detection of Fibrotic Gut Tissue in Patients with Stricturing Crohn Disease. Radiology 2015;275:889-99.
9. Catalano OA, Gee MS, Nicolai E, et al. Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of Inflammatory Strictures from Fibrotic Strictures in Crohn Disease. Radiology 2015:150566.
10. Khanna R, Bressler B, Levesque BG, et al. Early combined immunosuppression for the management of Crohn’s disease (REACT): a cluster randomised controlled trial. Lancet 2015.
11. De Cruz P, Kamm MA, Hamilton AL, et al. Crohn’s disease management after intestinal resection: a randomised trial. Lancet 2015;385:1406-17.
12. Vermeire S, Sandborn W, Danese S, et al. OP021. TURANDOT: a randomized, multicenter double-blind, placebo-controlled study of the safety and efficacy of Anti-MAdCAM Antibody PF-00547659 (PF) in patients with moderate to severe Ulcerative Colitis (UC). Journal of Crohn’s and Colitis 2015;9:S13-S13.
13. Sandborn W, Feagan BG, Wolf DC, et al. 445 The TOUCHSTONE Study: A Randomized, Double-Blind, Placebo-Controlled Induction Trial of an Oral S1P Receptor Modulator (RPC1063) in Moderate to Severe Ulcerative Colitis. Gastroenterology;148:S-93.
14. Sandborn W, Feagan B, Wolf D, et al. OP024. A randomized, double-blind, placebo-controlled induction trial of an oral S1P receptor modulator (RPC1063) in moderate to severe Ulcerative Colitis: Results of the TOUCHSTONE study. Journal of Crohn’s and Colitis 2015;9:S15-S15.
15. Monteleone G, Neurath MF, Ardizzone S, et al. Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn’s disease. N Engl J Med 2015;372:1104-13.