NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 11 | JANUARY 2014

NEWS & VIEWSIBD

Measuring what counts —endoscopic assessment in IBDReena Khanna, Barrett G. Levesque and William J. Sandborn

Endoscopic assessment in IBD provides direct visualization of the affected bowel mucosa. There is an important need for the meaningful measurement of these endoscopic images at the correct time point for medical decision-making and for clinical trials. European guidelines on endoscopy in IBD have recently been published.Khanna, R. et al. Nat. Rev. Gastroenterol. Hepatol. 11, 9–10 (2014); published online 3 December 2013; doi:10.1038/nrgastro.2013.233

Endoscopic assessment in IBD provides direct visualization of the affected bowel mucosa in the form of video imaging that needs to be meaningfully measured and uti­lized. In addition, important decisions need to be made about when and which endo­scopic assessment (upper endoscopy, colono­scopy, wireless capsule endoscopy, device assisted endoscopy and/or flexible sigmoido­scopy) should be performed. Although endoscopic assessments can provide valid information that affects clinical decision­making and about long­term outcomes, such as surgery and cancer, they also carry high costs, as well as the risks of inaccurate results and procedural complications. In addi­tion, an important need exists for validated endoscopic outcome measures in clinical trials in order to e fficiently identify potential new therapies.

Annese and colleagues from ECCO (European Crohn’s and Colitis Organ­isation) published the European evidence­based consensus for endoscopy in IBD.1 The systematic review and consensus state­ments provide an evidence­based approach for the use of endoscopy for the diagnosis, treatment, and identification of complica­tions in the clinical management of IBD. Although previous guidelines exist regard­ing endoscopy in IBD,2 the uptake of these prior recommendations has been sub­optimal. In a large multicentre survey that

evaluated 583 patients with longstanding ulcerative colitis, large discrepancies were observed in the practice of surveillance colonoscopy between centres.3 Overall, only 54% of eligible patients underwent surveillance for colorectal cancer.3 These findings underscore the need for additional guidance for practicing clinicians. The new guidelines incorporate current evi­dence and highlight evolving areas within the field, including assessing for endo­scopic disease activity to optimize clinical d ecision­making in an era of high­cost bio­logic therapies, the need for fit­for­purpose endoscopic indices in clinical trials, and the potential advantages of targeted sur­veillance and therapeutic endoscopy in IBD. The guidelines are well thought out and comprehensive, and the authors are to be congratulated.

We agreed with most of the statements in the guidelines, with the following excep­tions. First, it is unclear whether or not adult patients with paediatric­onset or adolescent­onset IBD should undergo an upper endoscopy with small bowel biopsy at the time of initial consultation by an adult gastroenterologist. Given that up to 50% of patients with paediatric­onset IBD can have evidence of upper gut disease, a clinician might want to firmly establish the current extent and severity of disease in these patients as they come into an adult gastroenterology practice in order to guide therapy. Second, the guidelines recom­mend that multiple biopsies from six seg­ments should be performed. Each set of biopsies at the time of diagnosis adds to the cost of care for IBD. The benefit of six

segments of biopsies compared to biopsies of the five colonic segments of the SES­CD (Simple Endoscopic Score for Crohn’s disease4) (ileum, right colon, transvers colon, sigmoid and left colon, and rectum) is unknown. Third, recommendations not to perform endoscopy during clinical remission are likely to evolve given that they are incongruent with using a treat to target strategy to achieve treat to mucosal healing and deep remission.5 Fourth, pouch endoscopy in our practice generally includes specifically performing biopsies of the pre­pouch ileum, pouch, and cuff to assess for Crohn’s disease, pouchitis, and cuffitis or dysplasia, respectively. Fifth, surveillance intervals at 2–3 years in ‘inter­mediate risk’ and at 5 years in ‘low risk’ patients with ulcerative colitis is unproven, and might be too infrequent compared with yearly surveillance.

Over time, the treatment of IBD has pro­gressed from the use of corticosteroids to targeted biologic agents, such as anti­TNF agents. Despite these advances, ~40% of patients who initially benefit from treat­ment with an anti­TNF agent lose response at 1 year.6 Owing to the limited number of biologic therapies available for IBD, and the expense of these agents, there is a need for informed decision­making. Management decisions based on clinical disease activ­ity scores, such as the Crohn’s Disease Activity Index (CDAI) introduce a subjec­tive component through patient­reported outcomes and symptoms. This symptom­based outcome measure has been shown to be nonspecific, as an elevated CDAI has been observed with other diseases, includ­ing IBS.7 For similar reasons, the use of CDAI­based outcomes has led to high rates of response to placebo in clinical trials.8,9 The use of serum and faecal inflammatory markers are limited by high rates of false positive and false negative results. However, endoscopy provides direct visualization of the inflamed mucosa, and has been asso­ciated with histologic healing, steroid­free

‘‘…an important need exists for validated endoscopic outcome measures… ’’

‘‘…endoscopy provides direct visualization of the inflamed mucosa…’’

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JANUARY 2014 | VOLUME 11 www.nature.com/nrgastro

NEWS & VIEWS

remission and low placebo rates, and can be used to predict long­term reductions in IBD complications. As a result of the increasing recognition of the pivotal role of endoscopy in the diagnosis, treatment, and surveillance of IBD, renewed interest has emerged regarding accurate identification and measurement of mucosal lesions and standardized reporting.10

Annese and colleagues from ECCO provide pragmatic evidence­based guide­lines for the use of endoscopy in the diagno­sis and treatment of IBD in daily practice. An evolution of treatment paradigms for treating to achieve mucosal healing seems likely both in clinical practice and in clini­cal trials. Along with that evolution we will need a refinement of endoscopic outcome measures, ideally evolving to the routine use of endoscopic disease activity instru­ments in clinical practice, for example, through their incorporation into endo­scopic reporting program software, as well as in clinical trials.

Division of Gastroenterology, Western University, 100 Perth Drive, London, ON N6A 5K8, Canada (R. Khanna). Division of Gastroenterology, University of California San Diego, 9500 Gliman Drive, La Jolla, CA 92093‑0956, USA (B. G. Levesque, W. J. Sandborn). Correspondence to: W. J. Sandborn wsandborn@ucsd.edu

Competing interestsR. Khanna declares no competing interests. B. G. Levesque declares associations with the following companies: Prometheus Labs, Santarus. W. J. Sandborn declares associations with numerous companies. See the article online for full details of the relationships.

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2. Byers, T., Levin, B., Rothenberger, D., Dodd, G. D. & Smith, R. A. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer. CA Cancer J. Clin. 47, 154–160 (1997).

3. Vienne, A. et al. Low prevalence of colonoscopic surveillance of inflammatory

bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort. Aliment. Pharmacol. Ther. 34, 188–195 (2011).

4. Daperno, M. et al. Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest. Endosc. 60, 505–512 (2004).

5. Bouguen, G. et al. Treat to target: a proposed new paradigm for the management of Crohn’s disease. Clin. Gastroenterol. Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.09.006.

6. Gisbert, J. P. & Panes, J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am. J. Gastroenterol. 104, 760–767 (2009).

7. Lahiff, C. et al. The Crohn’s disease activity index (CDAI) is similarly elevated in patients with Crohn’s disease and in patients with irritable bowel syndrome. Aliment. Pharmacol. Ther. 37, 786–794 (2013).

8. Schreiber, S. et al. Maintenance therapy with certolizumab pegol for Crohn’s disease. N. Engl. J. Med. 357, 239–250 (2007).

9. Hanauer, S. B. et al. Maintenance infliximab for Crohn’s disease: The ACCENT I randomised trial. Lancet 359, 1541–1549 (2002).

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