Professor David Rubin

Transmural healing should be a treatment aim in IBD and intestinal ultrasound (IUS) is uniquely positioned to help achieve that, AGW 2023 was told.

Professor David Rubin, chief of gastroenterology, hepatology and nutrition at the University of Chicago Medicine, told the meeting that IUS was a tool to help provide better patient care but was also valuable in understanding more about the disease process.

However IUS was still in its infancy, particularly in the United States, and there was a lot of work to do before current treatment goals were changed.

“The challenge is of course how deep can we go and what do you need to prove the deeper endpoints are better and practical. Can you actually achieve them and can you incorporate them into practice?,” Professor Rubin said.

He said the STRIDE-II consensus [link here], which he contributed to, confirmed short term targets of symptomatic relief and normalisation of CRP.

Longer term targets were endoscopic healing, normalisation of quality of life and the absence of disability. The consensus was that transmural healing in Crohn’s disease and histological healing in ulcerative colitis were not formal treatment targets but should be assessed as measures of the depth of remission.

“Symptom improvement is critically important for quality of life and it should occur early and that’s a good target but it’s not sufficient to guarantee disease control which requires something objective to document the inflammation is under control,” he said.

Professor Rubin said the limits to assessing transmural healing in both Crohn’s disease and ulcerative colitis have been largely due to the limits of the available technology.

“Intestinal ultrasound can visualise the various bowel wall layers in vivo and is becoming a key modality to measure structural bowel wall changes.”

Considerations for transmural healing to become an endpoint included:

• Clinical correlation between transmural disease and outcomes of interest
• Consensus definitions of transmural inflammation and healing
• Evidence that transmural healing improves with treatment
• Incorporation of measures of transmural healing into clinical trials
• Consensus statements and guidelines that translate evidence into clinical practice
• A trained, competent workforce with access to appropriate equipment.

He said the evidence was growing that transmural health was associated with improved long-term outcomes.

Avoid surgery and hospitalisation

In Crohn’s disease, where it has been studied the most, one study using magnetic resonance enterography [link here] has shown that transmural healing was associated with less surgery, fewer hospital admissions and reduced need for escalation of therapy.

Another retrospective study [link here] found patients with Crohn’s disease who achieved transmural healing as measured by IUS were more likely to avoid steroids, hospitalisation and surgery at one year, and had a longer time to clinical relapse.

Most recently, a study in ulcerative colitis [link here] had shown that transmural activity, as defined by the Milan Ultrasound Criteria, was better than endoscopic findings in predicting colectomy.

Professor Rubin said there was also growing evidence that transmural healing improves with treatment

For example, in a study of patients with moderate to severe ulcerative colitis starting tofacitinib treatment [link here], IUS was highly accurate in detecting treatment response when evaluated against endoscopic outcomes.

Professor Rubin said the SPIRIT consensus from the IOIBD [link here] had also determined that transmural healing may be a ultimate therapeutic goal and should therefore be measured in IBD disease modification trials.

“We need to do some more work,” he said.

Questions that still to be answered included:

• Is transmural healing better than endoscopic healing?
• If and when to de-intensify treatment when transmural healing is achieved?
• The timing of complete transmural healing?
• Does transmural healing in the small bowel mean something different to transmural healing in the colon?
• Does transmural inflammation in the colon and rectum predict neoplasia?
• Do symptoms correlate better to transmural healing than to endoscopy or histology?