Ryan Ungaro, MD, on Treat-to-Target: Is It All About the Mucosa?

Ryan Ungaro, MD, gives a recap of his presentation on treat-to-target in inflammatory bowel disease from the virtual Advances in Inflammatory Bowel Disease regional meeting on June 27. 

Ryan Ungaro, MD, is assistant professor of gastroenterology at the Icahn School of Medicine at Mt. Sinai in New York.


I’m Ryan Ungaro, assistant professor of gastroenterology at the Icahn School of Medicine at Mount Sinai in New York. At this past AIBD Regionals Conference on Saturday June 27, I gave a talk on "Treat‑to‑Target: Is It All About the Mucosa?"

During this talk, I focused on what is treat‑to‑target? A number of points to take home for clinicians I want to highlight. Number one, what is treat‑to‑target?

This is where we now take a new approach to IBD care, where we go beyond symptoms. Not just how the patient is feeling, because we know there is a discordance between what symptoms patients are having and objective metrics of inflammation, but in addition to symptoms, adding objective markers, specifically endoscopy, to our assessment of our patients reaching remission.

The new guidance based on the STRIDE recommendations—but it's been around out for a few years, but is trying to be implemented more regularly in daily practice—is that our target thriving patients should not be symptoms alone, but should be a composite of resolution of symptoms and resolution of endoscopic inflammation by colonoscopy and/or imaging, in certain Crohn’s patients.

Preferably, endoscopic healing in both UC and Crohn's in addition to the symptom resolution. So this 2‑tiered approach where it's not just symptoms, it's also objective metrics.

Next, we talked about reaching the target of endoscopic healing, what long‑term impact does that have for patients? We reviewed some meta‑analyses from CGH as well as APT, looking at UC and Crohn's. Patients who had endoscopic healing in both UC and Crohn’s disease were more likely to be in steric through remission out to a year and were also less likely to have IBD‑related surgeries out to a year as well.

Newer data from our group at Mount Sinai, that I also reviewed, showed that in patients with Crohn's disease who are recently diagnosed—so this is an early Crohn's disease—if you're able to reach the target of endoscopic remission, and even further deeper remission, which would be no symptoms, no endoscopic lesions, that those patients over the long term after 3+ years of follow-up, had very few complications.

If you're able to reach your target of endoscopic remission or deep remission—I think even better deep remission—you can actually alter the longer‑term disease course for patients with Crohn’s disease, with significantly fewer complications such as hospitalizations, surgeries, or new strictures and fistula.

Last, we spoke about how do we actually get to the target? We know that reaching the target of endoscopic healing, in addition to symptom resolution, is the new target. But if you reach it, how do you get there? What's the best way to get there?

We reviewed data from the seminal CALM trial, which was published in The Lancet a couple years ago now, in which patients were randomized to either a tight‑control arm vs a conventional arm. In the conventional arm, patients’ treatment was escalated based on symptoms alone. Whereas in the tight‑control arm, patients’ symptoms were incorporated as well as objective markers of inflammation, such as CRP and fecal calprotectin. So if you're in the tight‑control arm and you're feeling well, but your fecal calprotectin or CRP is elevated, your therapy was escalated.

Taking this approach of serial monitoring of patients, and including objective markers of inflammation, to make decisions about adjusting our patient's therapy proactively. What the CALM study showed is that, if you incorporate objective metrics every 3 months into your assessment of patients with Crohn’s disease, that you're more likely to be in endoscopic and deep remission in one year than patients with Crohn’s disease.

The take‑home from this study and from the talk is that once a patient is starting a new therapy, physicians should be checking in and up with patients a minimum every 3 months, asking about the symptoms but also checking the CRP and fecal calprotectin. If objective markers of inflammation are not getting better, then adjusting therapy.

Within 6 to 12 months of starting a new therapy, patients should have a repeat colonoscopy to assess that they are achieving that metric of endoscopic healing. The treat‑to‑target era is now here and is something that we can be implementing for all our IBD patients.

In the future, beyond the endoscopic healing, it's possible that we'll be looking at targets such as histologic healing or even molecular healing. Not just that the scope looks good but even on the biopsy or some molecular say that the patient is doing better. Although, those are not yet ready for prime time. We highlighted a couple studies that suggest that in the future, these could be potentially new targets.

In our daily practices, we should be incorporating these objective metrics and endoscopy, in our routine assessments of our IBD patients’ disease activity. Thank you.