Marla Dubinsky, MD, on Biomarkers for the Optimization of IBD: Finding Precision

In this podcast, Marla Dubinsky, MD, discusses the highlights from her presentation on using biomarkers to enhance precision and optimize therapy for inflammatory bowel disease, which she discussed at the AIBD regional meeting on September 11.

Marla Dubinsky, MD, is the codirector of Susan and Leonard Feinstein IBD Clinical Center at the Icahn School of Medicine at Mount Sinai Hospital in New York City.

TRANSCRIPT

Dr. Marla Dubinsky:  Hello, I'm Dr. Marla Dubinsky. I want to provide a summary of the lecture that was given as part of the regional Advances in Inflammatory Bowel Diseases conference entitled, "Biomarkers for the Optimization of IBD and Finding Precision."

We know that we are in a time in IBD where the ability to be proactive, predict flares, be able to practice proactive IBD care is only going to lead to better outcomes for our patients.

This requires us thinking about different domains of where biomarkers may be helpful to be able to practice this exciting proactive IBD care currently in our strategies of treating IBD. We could think about biomarkers and IBD along three buckets in the spectrum of where they're most helpful.

One, prognostic biomarkers, the ability to predict a patient who's going to end up in surgery having a complication due to their disease, most notably, for example, in Crohn's disease, be able to use serologic immune markers, potentially the role of genetics in the future.

Some way of understanding why this is the patient that I need to intervene early, meaning effective therapy early, so that we can minimize the risk of developing a complication due to the disease itself.

The next bucket of biomarker application is in predicting treatment response, meaning, are there tools, biologic markers, biomarkers of inflammation, even radiologic markers, such as a small bowel ultrasound that's being looked at in real-time point-of-care in the clinic?

Essentially, there's been different research looking at whether or not there are certain gene-expression markers. For example, there was a study that looked at the anti-TNF therapies in ulcerative colitis that found that oncostatin-M expression predicted lack of response to anti-TNF therapy.

The question is, are these actual markers truly related to disease -- response or non-response -- or are they a marker of how sick and severe the inflammation is that that alone is more important than saying, "This patient will have a difficult time responding to therapy"?

There's been some other biologic markers. There was even looking at the role of IL-22 as a predictor of response, meaning baseline, before you got the therapy with the therapy-of-interest study is the IL-23 or the p19 monoclonal antibody.

Suggesting that what you have at baseline may predict whether you're going to be a good candidate to receive IL-23, and there are other gene expression markers that have been looked at, even in vedolizumab. This is an area that we require a lot more research and a lot more information on how to predict treatment response.

The final category that I focused on during the lecture was on monitoring treatment response. This gets to the role of fecal markers or other blood markers, non-invasive ways of monitoring response to treatment, particularly in the induction period.

Not everyone wants to be scoped at 8 weeks, or 10 weeks, or 12 weeks like the clinical trials are doing. We're looking for non-invasive ways of tracking response to treatment, looking at the true inflammatory burden.

Calprotectin is probably one of the most studied biomarkers that have been shown that even if you can get to a calprotectin of less than 250 already at eight weeks—and vedolizumab or ustekinumab as it relates to ulcerative colitis, for example—it's proposed that is a sign that your patient is heading in the right direction.

I did mention the role of small bowel ultrasound. At DDW, there is a lovely study looking at the impact on bowel wall thickness and hyperemia using Doppler color signal to look at the change before tofacitinib, and then the bowel wall eight weeks after receiving tofacitinib.

Showing you can predict response, and they even compared it to colonoscopy, showing a very high-predictive value of changes in cross-sectional imaging in the clinic. This is a really exciting direction.

Dr. Dolinger spoke about the role of point-of-care ultrasound. You're going to see a lot more of that as a biomarker, or non-invasive marker of inflammation, or shall I say the biology of inflammation in the gut wall.

This is a very exciting time in the proactive IBD management spectrum of strategies for approaching the management. This is the start of something exciting, and I look forward to bringing you more updates on the role of these non-invasive ways to implicate biomarkers into the management of IBD. Thank you.