In this video, Dr Horst gives a recap on her presentation at the AIBD Regional 2022 Virtual Meeting on April 30 on when to optimize treatment and when to switch therapies when managing patients with inflammatory bowel disease.

Sara Horst, MD, is an Associate Professor in the division of Gastroenterology, Hepatology, & Nutrition at Vanderbilt University Medical Center. 

TRANSCRIPT

Sara Horst, MD:
Hi, I'm Sara Horst. I'm a gastroenterologist at Vanderbilt University Medical Center who specializes in the care of patients with inflammatory bowel disease. I was really excited to talk about a topic, to optimize or to switch, that is the question, for the recent AIBD regional course. I think this is a super important topic as more and more biologics and more molecule medications are becoming available. And so we'll talk through my topic. We wanted to do this case based, so I'll run through the two topics, or the two cases that I went through in my talk.

So the first one was a patient with Crohn's disease who started adalimumab and did really well for a period of three to six months, unfortunately, started to flare. A scope, showed significant recurrent disease. The patient had to start prednisone. And so the question was, what's the next step?

And in thinking about this, I think this is when we can start talking about therapeutic drug monitoring, especially in inflammatory bowel disease. It's important to remember that 30% of patients with inflammatory bowel disease could be primary non-responders, but a lot will have loss of response and a significant number of this maybe because of subtherapeutic drug levels or anti-drug antibodies. Patients develop anti-drug antibodies. We know that they have... If they have higher drug, excuse me, if they have higher drug levels, we know across many studies that the patients have a higher likelihood to have endoscopic improvement, biochemical improvement, histologic improvement and feel better, so it's pretty important. In 2017, the AGA suggested that reactive therapeutic drug monitoring to guide treatment changes for patients with inflammatory bowel disease is important.

Different drug levels are sometimes difficult, so I talk through how there are some certain drug levels, but it might be important to think about more when you check the drug level, and what is your therapeutic outcome? Are you looking for more clinical remission or endoscopic healing? And there was a recent updated consensus with Adam Cheifetz and colleague who talk about this, and so we went through that, just think about what kind of drug level you're shooting for. Our patient had a drug level checked and unfortunately had no drug level and very high anti-drug antibodies.

So we talked through what to do next. Options would be to think about for this patient with Crohn's disease, staying in class, staying with an anti-TNF, using anti-TNF alone, or should we use anti-TNF plus immunomodulator, or should we think about a new mechanism of action? And I highlighted that there's actually some data showing that if you go to a second anti-TNF, because a patient fails because of low drug level or antidrug antibodies, it's very important to use an immunomodulator. And actually there is data to suggest that patients who go on a second anti-TNF and use immunomodulator therapy have improved clinical outcome and lower rates of anti-drug antibodies.

So if this patient was to stay within class, I would advocate that if they started infliximab or a biosimilar, that they also start an immunomodulator therapy with that. And other options would be to try to keep the patient on the drug longer. Think about if proactive drug monitoring would be an option. That's a little bit still controversial, although we think, especially for someone who may have lost response because of having low drug level or making anti-drug antibodies, it's probably important to think about it at least once in that patient. And some people would advocate further early proactive drug monitoring.

So then we thought about, well, what if we're going to switch out of class, what would be options? And there is some data to suggest, and there's a consortium called the Evolve Consortium, where they looked at patients who did first-line vedolizumab versus second-line... had first-line vedolizumab and then went to an anti-TNF, versus using first-line anti-TNF. And when they compared those two groups, they actually found that patients who've done first-line vedolizumab had very similar rates of treatment persistence and clinical effectiveness if they used anti-TNF second-line. So there's some data to show if you use the [illuzumab 00:04:40] first in someone with Crohn's disease, that you could still maintain similar clinical response to the second-line biologic, which is sort of different than we've seen in prior phase clinical trials. So that was really good data to have.

There have been some pro prospective registry studies done in Europe. One was a Dutch registry, another one a French registry, looking at patients who used ustekinumab versus vedolizumab in Crohn's disease second-line, so after its anti-TNF. Both of these studies suggested a little differential benefit with ustekinumab over vedolizumab at week 42. Again, it's retrospective data, and there could be some bias as to who was put on vedolizumab versus ustekinumab, but there's a little bit of data in the real world to suggest a bit of a differential of ustekinumab over vedolizumab. And in network meta-analysis and looking at positioning biologics for Crohn's disease, again, in that network, that analysis ustekinumab may edge out vedolizumab a bit when using these drugs after anti-TNF therapy.

When I thought through this, I think we, in thinking about that patient, if you're going to use another anti-TNF, make sure to use immunomodulator therapy and think about continuing to be vigilant about drug monitoring for that patient. Vedolizumab has some real world data to suggest no difference in anti-TNF success after first-line vedolizumab use. And there's a little bit of real world data and a network and analysis to suggest that ustekinumab may edge out vedolizumab in a second biologic for someone with Crohn's disease after anti-TNF failure.

So it was really exciting to think about this, and I think the landscape may change in the next three to five years as more drugs become available for patients who failed anti-TNF in the real world, but it was really great to think about patients. Thank you so much and we look forward to seeing you at our next AIBD regional course. Thanks.