Are we ready to use activity scores for intestinal ultrasound in ulcerative colitis?

The use of intestinal ultrasound as a non-invasive diagnostic tool plays an increasing role in monitoring patients with Crohn's disease.1-3 The role of IUS in ulcerative colitis (UC) is less well-established. However, mounting evidence suggests its use is reliable, objective, more patient-centered, and easily used to determine disease activity as well as disease extension in UC as well.4-7 The study by M. Allocca et al.8, 9 published in this issue provides external validation of the recently developed Milan Ultrasound Criteria (MUC) to assess disease activity and severity in UC. The key findings of this study are in agreement with the author's previously published results demonstrating the discrimination of active versus inactive disease by a threshold MUC score more than 6.2 (sensitivity of 0.85 [95% confidence interval (CI): 0.66–0.96], specificity of 0.94 [95% CI: 0.70–0.99], and an area under the curve [AUC] of 0.902 [95% CI: 0.772–0.971]). Colonic wall thickness (CWT) and vascularity or flow within the colonic wall (CWF) assessed by color Doppler, were the most important features to assess disease activity to the MUC. This study confirmed that both CWT more than 3 mm coupled with CWF, or CWT alone as a single parameter (cut-off > 4.43 mm) indicate active disease. AUC and cut-off values for the criteria are similar in both derivation and validation cohorts indicating good reproducibility of the findings. This small cohort validation study is well performed and supports the use of the MUC for disease activity assessment in UC using intestinal ultrasound. It also strengthens the relevance of standardization of measurement of IUS findings. Developing simple scores to determine disease activity as demonstrated here, is a crucial step towards standardizing assessment for IUS for monitoring UC and expanding adoption. This study also demonstrates how easy it is to detect disease activity of UC by IUS, simply revealed by an abnormally thickened colonic wall (>3 mm) coupled with increased vascularization. Interestingly, addition of fecal calprotectin (FC) did not significantly increase the sensitivity and specificity of the MUC, thus calling into question the added value of FC with IUS in treatment decisions. These findings are also consistent with the derivation study. Larger cohorts are important to confirm the relative contribution of FC to IUS in this setting. Patients with UC limited to the distal colon (E1) were excluded in the derivation study and therefore the accuracy reported in assessing activity in this study will not accurately reflect all those in the general UC population. The addition of FC may increase sensitivity, particularly in those patients with proctitis, where IUS shows lower sensitivity. Another option would be to perform transperineal ultrasonography (TPUS) in patients with E1 phenotype, recently been shown to be an accurate and easily performed technique to detect active inflammation of the rectum, applying the same probes used for abdominal ultrasonography.10 The questions remain, however, of whether or not a score is needed to simply discriminate active versus inactive disease, or whether a responsive, reliable and valid score that reflects different degrees of disease activity is not superior. This advantage is currently offered by endoscopic evaluation, and for this reason endoscopy will likely remain the reference standard for assessing UC activity. IUS may conversely offer the advantage of discriminating active disease from chronic changes within the bowel wall, which cannot be assessed by endoscopy. Data from a large multicenter trial in patients with active UC, demonstrated response in bowel wall thickness using IUS as early as 2 weeks after treatment initiation in a significant proportion of patients.5 Recent data employing TPUS in patients with ulcerative proctitis demonstrate excellent correlation between ultrasonographic and endoscopic parameters.10 In this study, treatment response was detected within 1 week after treatment initiation, further supporting the early use of IUS/TPUS in monitoring active UC patients. The growing body of evidence supporting the accuracy of IUS, together with this first validation trial of the MUC, further supports the utility of IUS in monitoring disease activity in IBD and may strengthen broader application. It is time to include IUS UC activity scores as secondary objectives in therapeutic drug trials, using IUS central reading. Larger and additional independent cohorts further evaluating this simple and applicable score, including those with limited distal disease may also aid in understanding the additional utility of FC. The now partially validated MUC helps to encourage wider implementation of IUS as a cost-effective, noninvasive, safe and easy to use diagnostic tool that may reduce the number of invasive colonoscopies used for monitoring UC disease activity in the future. T. K. received honorary from Abbvie, Amgen, Arena, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Galapagos, Gilead, Dr. Falk Pharma GmbH, Ferring, Hospira, Janssen, MSD Sharp & Dome GmbH Mundipharma, Takeda Pharma GmbH. C. M. received honorary Abbvie, Arena, Biogen, Cellgene, Ferring, Galapagos, Gilead, Dr. Falk Pharma GmbH, Janssen, MSD Sharp & Dome GmbH, Pfizer, Takeda Pharma GmbH. K. N. received honorary from Abbvie, Takeda, Janssen, Pfizer, and Pendopharm. Torsten Kucharzik prepared the first draft of the editorial. Christian Maaser prepared second draft of the editorial with includes further relevant aspects. Kerri Novak finalized the editorial with including further relevant aspects.

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