A TIGER Among Endoscopic Indices in Inflammatory Bowel Disease

Endoscopy is central to the contemporary management of inflammatory bowel disease [IBD]. Endoscopic remission is both a long-term treatment target in daily clinical practice1 and a key component in clinical trials for regulatory approval of novel therapeutic agents.2 Moreover, it is not inconceivable that payers may also base decisions about ongoing treatment reimbursement on endoscopic assessment. Thus validated endoscopic indices enabling standardised, reproducible, and uniform reporting are essential for clinical practice and an integral part of the clinical trial landscape. Despite the widespread use of the Simple Endoscopic Score for Crohn’s Disease [SES-CD]3 and the Mayo Endoscopic Score [MES] in ulcerative colitis [UC],4 these indices are not without limitations which may result in the loss of clinically potentially relevant details about disease extent and activity. Reflecting the patchy and discontinuous nature of CD, the SES-CD is scored by segment, with the total score representing a sum of segmental scores. By case example, a total score of 9 points can be reached in a single severely diseased segment with very large ulcers [3 points], affecting 50% of the segment [3 points] and a total diseased surface area of >80% [3 points]. Alternatively, the same score can be reached by three segments with small aphthous ulcers [1 point], involving 5% of an individual segment [1 point] and a total diseased surface area of 5% [1 points]. In an extreme scenario, three aphthous ulcers spread across three colonic segments could result in a score equal to that of heavily ulcerated segment, which highlights the shortcomings of the SES-CD in accounting for disease burden. The MES was designed to be scored as observed, defaulting to the score of the worst affected segment. Nonetheless, the MES thus neglects clinically important changes in disease burden: a change in MES from 3 to 2 grossly understates the evolution from pancolitis with ulceration to a healed colon with a single persistent erosion in the rectum. The MES also disregards directionality and extent of healing; for example, healing from MES 3 pancolitis to MES 3 proctitis would be considered treatment failure within the setting of a clinical trial. Finally, the MES is also incompletely validated despite being in use for more than three decades. In this issue of the Journal, Zittan and colleagues describe the development and initial validation of a novel endoscopic index, the Toronto IBD Global Endoscopic Reporting [TIGER] score.5 The index was developed with a cross-sectional cohort of 40 patients [20 CD, 20 UC] with varying endoscopic disease activity. Notably, patients with postoperative CD and those with endoscopically inaccessible disease were ineligible for the study. Using a conceptually novel approach, the authors have combined individual component items from established indices to develop a new score, agnostic of IBD type: general appearance of mucosa from MES [0–3 points] and four variables from the SES-CD—ulcer/erosion size [0–3 points, same cut-offs as SES-CD], percentage of ulcerated/eroded surface [0–3 points, same cut-offs as SES-CD], presence of narrowing [0–3 points, same cut-offs as SES-CD], and the percentage of affected surface [0 or 1 point with cut-off at 50%]. Scoring was performed per segment and points are added for segments with at least moderate endoscopic activity [≥5 points on the TIGER score, excluding points derived from luminal narrowing]. The score was shown to correlate with faecal calprotectin [correlation stronger in UC than CD], C-reactive protein [only CD], and, perhaps most importantly, with IBD-related disability as evaluated by the IBD Disk. Not unexpectedly, there was moderate to substantial agreement between the TIGER score and MES and SES-CD, respectively, when evaluated at the level of an individual segment. Finally, the reliability of the index was good among the three expert endoscopists involved in the index development process. The TIGER score has a number commendable properties, which set it apart from its ‘parent’ indices. First, it includes all visualised segments, which is a step forward in the endoscopic scoring of UC, as the score also accounts for disease extent and is more straightforward to calculate than previous attempts to capture disease extent.6 Second, adding 100 points for each segment with at least moderate endoscopic activity enables immediate distinction, in contrast to the SES-CD, between disease with a single severely affected segment and disease with three mildly affected segments, as the first digit of the TIGER score denotes the number of segments with moderate or severe endoscopic activity. This may also hold additional prognostic value, as there is some indication that the size of ulcers in CD, particularly in the ileum and rectum, rather than the total SES-CD score, is more closely associated with the likelihood of achieving subsequent endoscopic remission.7 Finally, this is the first disease-agnostic endoscopic index, which may help contribute to wider uptake in daily clinical practice, fuelled by its relative simplicity. Limitations of the TIGER score should also be acknowledged. Assessment of luminal narrowing has been shown to have low inter-rater reliability8 and responsiveness9 in CD, at least in the context of central reading in clinical trials. Points from narrowing do not contribute towards the segmental point total to award bonus points for severity, which was justified by the fact that fibrotic stenoses do not necessarily indicate the presence of inflammation. Ideally, the contribution of stenosis to the operating characteristics of the new index should be explored in further validation studies. Finally, the segmental cut-off for awarding bonus points for severity appears to have been based on SES-CD thresholds for endoscopic severity, which are mostly arbitrary and incompletely validated. In summary, the TIGER score is an original and welcome step forward towards further refinement of endoscopic assessment in IBD, for which the authors are commended. Further validation within larger cohorts or clinical trials is warranted, Additional areas of research interest include validation against histology for UC and the potential for its use in postoperative CD. None. JH received speaker’s fees from Abbvie, Janssen, and Takeda, and consulting fees from Alimentiv Inc. VJ has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc. [formerly Robarts Clinical Trials], Arena Pharmaceuticals, Asieris, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Reistone Biopharma, Roche, Sandoz, Takeda, Topivert, and speaker’s fees from Abbvie, Ferring, Janssen, Pfizer, Shire, Takeda. JH and VJ both wrote and critically revised the manuscript.

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