Redefining IBD Care: Intestinal Ultrasound’s Emerging Role in Treat-to-Target Strategies

With the rapid evolution of inflammatory bowel disease (IBD) therapeutics in recent years and a growing understanding of the underlying mechanisms of the disease, treatment goals are changing and expanding, most recently with the introduction of treat-to-target.¹

In the past, IBD management approaches were hampered by the efficacy of the drugs available at the time and an inability to achieve deeper healing beyond symptomatic relief. The ability to both measure and achieve endoscopic healing fundamentally reshaped the concept of disease management for patients with IBD, with the idea of treat-to-target formalized in 2015 in the first Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guideline.^1,2

Initiated by the International Organization for the Study of Inflammatory Bowel Diseases, the STRIDE guideline provides evidence- and consensus-based recommendations for treating patients with IBD, specifying short-, intermediate-, and long-term treatment goals tailored to individual needs and local resources. It was later updated in 2021 to incorporate therapeutic goals for treat-to-target strategies in both adult and pediatric IBD.^2,3

The update, coined STRIDE-II, confirmed STRIDE long-term targets of clinical remission and endoscopic healing but added absence of disability, restoration of quality of life, and normal growth in children. Additionally, symptomatic relief and normalization of serum and fecal markers were deemed short-term targets and, despite not being formal targets, transmural healing in Crohn’s disease (CD) and histological healing in ulcerative colitis (UC) were suggested as measures of remission depth.³

“When we published the STRIDE II guidance doubling down on endo as being an important outcome, it was very satisfying to see that there was at least a box that said the future of Crohn's might include transmural healing or remission, which to me is STRIDE-III,” Marla Dubinsky, MD, chief of the division of pediatric gastroenterology at Mount Sinai Kravis Children’s Hospital, explained to HCPLive, expressing hope for progress toward an updated guideline encompassing “the emerging evidence of the role of intestinal ultrasound.”

A non-invasive, cross-sectional imaging tool, intestinal ultrasound can be used at the point of care to assess disease activity with high-resolution visualization of the bowel, including the colon and the small intestine. By examining bowel thickness as a measure of inflammation in real time, clinicians are able to evaluate treatment efficacy and disease progression more efficiently.⁴ Of note, intestinal ultrasound allows for the assessment of transmural healing, a target suggested but not formally endorsed in STRIDE-II.³

Despite her desire for new guidance reflecting the latest research for intestinal ultrasound, Dubinsky pointed out that the real-world implementation of STRIDE recommendations has not been immediate, citing the fact that no drug being tested in a clinical trial was held to a bar beyond Crohn's disease activity index (CDAI) remission until 2022 with risankizumab, when she says we “finally caught up with our treat to target strategies.”

ADVANCE and MOTIVATE were randomized, double-masked, placebo-controlled, phase 3 induction studies used to support the US Food and Drug Administration’s approval of risankizumab-rzaa (Skyrizi) in patients with moderately to severely active CD. Co-primary endpoints included clinical remission, defined by CDAI or patient-reported outcome criteria (average daily stool frequency and abdominal pain score), and endoscopic response, measured by Simple Endoscopic Score in CD, at week 12.⁵

Beyond the clinical trial space, clinicians are widely implementing the STRIDE-II suggested treat-to-target approach in everyday practice, with recent years seeing a growing interest in the utilization of intestinal ultrasound due to its various benefits over current conventional approaches to IBD monitoring and their subsequent alignment with STRIDE guidance.

In an interview with HCPLive, Michael Dolinger, MD, MBA, assistant professor of pediatric gastroenterology at the Icahn School of Medicine and Mount Sinai Kravis Children's Hospital, explained intestinal ultrasound is not formally part of the STRIDE-II consensus, but it could serve as a viable noninvasive marker of response to help guide early treatment optimization to achieve treat to target outcomes within a year, as suggested in STRIDE.

Adelina Hung, MD, clinical assistant professor at Rosalind Franklin University Chicago Medical School and director of the IBD program at Sinai Health System Chicago, told HCPLive she believes intestinal ultrasound “could fundamentally change the management of IBD care" because it "has potential to be used as the earliest modality of treatment response. It's noninvasive, doesn't require prep, fasting, sedation or anesthesia, you can perform imaging as often as you need with minimal to no concern for risk of adverse events, and it's much more affordable than traditional imaging options – a key consideration for resource limited settings with high IBD burden."

Although intestinal ultrasound is an emerging imaging modality in the United States, it has been the standard of care in Canada and many parts of Europe for the past decade.⁶ Noa Krugliak Cleveland, MD, assistant professor of medicine in the section of gastroenterology at the University of Chicago, described how the push to incorporate intestinal ultrasound into the current IBD care model in the US is being pioneered by a few leading institutions, including the University of Chicago, Mount Sinai, and the University of Calgary, all of whom were able to work together to receive grant funding to bring intestinal ultrasound education and training to the US.

“I would say that about 4 years ago, there was almost nobody that was performing intestinal ultrasound in the United States, at least not among the gastroenterologists and IBD specialists,” she explained. “Between 2019 and 2021 is when the first group of gastroenterologists went to Europe and started getting trained by the International Bowel Ultrasound Group.”

Despite not being formally endorsed in the STRIDE guidance, many believe intestinal ultrasound could be a promising option to support some of the strategies and approaches suggested in the consensus, with more and more clinicians receiving the training necessary to support the tool’s widespread implementation in clinical practice.

“We're trying every monitoring strategy to do better for our IBD patients, and this is where ultrasound has come in,” Dolinger said. “I think the recognition that ultrasound is a direct monitoring tool of inflammation can really be transformative to how we manage our IBD patients by allowing us to see inflammation we weren't detecting before and to optimize treatments before it's too late.”

Krugliak Cleveland expressed a similar sentiment, describing intestinal ultrasound as being “unlike any other tool we currently have” and citing its utility during every stage of disease management, from diagnosis to prognosis and monitoring treatment response. She additionally pointed out its ability to support tighter disease monitoring and deeper targets of healing without the discomfort or expense of other commonly used modalities.

“[Intestinal ultrasound] has completely changed my practice, and I think it's going to change everybody's practice,” said Dubinsky.

References:

1. ^{Kyriacou M, Vuyyuru S, Moran G. Evolution of Treatment Targets in Inflammatory Bowel Disease. Medical Research Archives, 11(11). doi:10.18103/mra.v11i11.4662}
2. ^{Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target. Am J Gastroenterol. 2015;110(9):1324-1338. doi:10.1038/ajg.2015.233}
3. ^{Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031}
4. ^{Dolinger MT, Kayal M. Intestinal ultrasound as a non-invasive tool to monitor inflammatory bowel disease activity and guide clinical decision making. World J Gastroenterol. 2023;29(15):2272-2282. doi:10.3748/wjg.v29.i15.2272}
5. ^{Walter, K. FDA Appropves Risankizumab For Crohn’s Disease. HCPLive. June 22, 2022. Accessed May 29, 2024. https://www.hcplive.com/view/fda-appropves-risankizumab-crohns-disease}
6. ^{University of North Carolina School of Medicine. Revolutionizing IBD Care: The Power of Intestinal Ultrasound. Gastroenterology and Hepatology. January 29, 2024. Accessed May 29, 2024. https://www.med.unc.edu/medicine/news/revolutionizing-ibd-care-the-power-of-intestinal-ultrasound/}