Optimizing Treatment Strategies to Manage Inflammatory Bowel Disease - Episode 10

Biologics Used in the Treatment of IBD

September 16, 2021
Remo Panaccione, MD, FRCPC

William Sandborn, MD

Edward Loftus Jr., MD

Jessica Allegretti, MD, MPH

A panel of experts share their experiences with the use of biologics for the treatment of inflammatory bowel diseases (IBDs).

Remo Panaccione, MD, FRCPC: Bill, let’s start with you. Discuss the various classes of biologics that we use in the treatment of IBD [irritable bowel disease] broadly by mechanism of action, and your experience with them.

William Sandborn, MD: I have transitioned my nomenclature to talk about biologics and other advanced therapies. We have the TNF [tumor necrosis factor] blockers. We have 3 each, for UC [ulcerative colitis] and Crohn. We have anti-integrin therapy with vedolizumab. We have anti-interleukin-12/23 therapy with ustekinumab. Then, we have JAK [Janus kinase] inhibitor therapy with tofacitinib for ulcerative colitis. As of recently, we have S1Ps [sphingosine-1-phosphate modulation] for ulcerative colitis. So, we have 5 classes of drugs now for ulcerative colitis and 3 classes for Crohn disease. Then, coming along are the anti-interleukin-23 drugs for Crohn, which will be another class of drugs for the treatment of Crohn.

We’ve gone from anti-TNFs—which, for those of us that are older, that’s almost half of our professional life—to all these other classes. Unfortunately, there are few head-to-head trials. We have the VARSITY trial that compared adalimumab to vedolizumab in the treatment of UC, which showed that, for anti-TNF-naive patients, vedolizumab was better for response remission. Then, you have the recent SEAVUE trial comparing adalimumab and ustekinumab in patients who are biologic naive with Crohn disease that showed similar outcomes. Everything else is network meta-analysis and cross comparing trials. You have to practice, so you end up doing it, but it’s not satisfying.

Remo Panaccione, MD, FRCPC: What are the strengths and weaknesses of each class? How do you see them?

Edward Loftus Jr, MD: With the anti-TNFs, they’ve been around the most and, in my own practice, anti-TNFs are great drugs to treat Crohn, and they’re OK to treat UC. Usually, we don’t get too much insurance pushback if we need to dose-escalate these drugs. There is that familiarity. We get the added benefit of fistulas. The biggest downside is immunogenicity and loss of response.

Vedolizumab is a great drug to treat UC. It may be OK to treat Crohn for that early, bio-naive moderate patient. Anecdotally, I’ve seen patients respond well to it. One of the nice features of vedolizumab is the safety profile. The downsides are extraintestinal manifestations. Patients with arthralgias continue to have arthralgias. Ustekinumab is my favorite drug to treat Crohn with. By the time it got approved for Crohn, there was so much off-label use and clinical trial use, it felt like it was a familiar drug already. Tofacitinib is potent, rapid, and easy to take orally, but there are some concerns about the safety profile—there’s explaining it to the patient. But on the other hand, we’re going to have some of the selective JAK1s [JAK1 inhibitors], which are promising.

Jessica Allegretti, MD, MPH: The unfortunate truth of the matter is that payers dictate so much of what we do. Maybe I would be using ustekinumab more as a first-line treatment if it wasn’t so difficult for me. Unfortunately, that does affect your practicing pattern. I’m curious to see where I start to incorporate ozanimod in my practice and how the monitoring of that agent will go. That will also suffer from some of the same problems tofacitinib has in explaining some of the potential risks to patients. The patients like oral medication. Oral is easy and convenient, but we must balance that with some of that explanation [about] some things that are foreign to GI [gastrointestinal] doctors and how to explain and monitor for those potential risks with these newer small molecules. Overall, having a fifth class for ulcerative colitis is fantastic. I’m excited about the selective JAKs. I have participated in many trials for the treatment of Crohn disease and see the promise. There is a lot of good stuff on the horizon.

Remo Panaccione, MD, FRCPC: When you have somebody who started on an anti-TNF as your choice, what are your expectations and how do you monitor them? Do you have a systematic way, for patients with Crohn disease and ulcerative colitis, of monitoring them?

Jessica Allegretti, MD, MPH: Yes; let’s use infliximab as an example. Once I have a patient started, hopefully, we have done some baseline assessments. I have imaging. I have fecal calprotectin. I have things I’m going to follow, because I subscribe to the treat-to-target metrics. I pick targets up front for that patient, and I plan on following them. I also do a lot of therapeutic drug monitoring in my practice. I always get a trough level before that third loading dose because I like to make sure, as we’re going into maintenance, to answer this: Do I potentially need to dose-escalate or do something different? I always see the patients back after the third loading dose to assess for clinical response. Are we starting to see improvement? If not, I’m trying to figure out why have they developed antibodies. I have recently gotten those level and antibody tests, so I can assess that, and I’m trying to understand: Are they underdosed? Do they need to dose-escalate? If they’re already showing rapid improvement, if they’re doing well, then I’m ensuring that I feel comfortable with the maintenance dose that they’re on, that I’ve done therapeutic drug monitoring on the immunomodulator that they’re on, and that all the dosing is appropriate.

Typically speaking, I’m doing some additional assessment aside from clinical response, whether that be fecal calprotectin, an image, or an endoscopic exam at some point between, say, 3 and 6 months, depending on which disease we’re talking about. I’m always first looking at the clinical side, making sure my dosing is correct and making sure the patient is improving as I would expect. If not, I’m sorting out why. We can get into the various reasons why that might not be. Then, I’m always confirming what I’m doing with an objective marker. Again, these are the targets I would have set out at the beginning. I explain this to patients. I say, “I want you to feel well. It is important, but we also need to be checking these other things to make sure that you’re progressing as we would expect. Have you achieved mucosal healing? Has your MRI normalized? Is your fecal calprotectin coming down?” I do this so that they’re along for the ride with you and it doesn’t feel like a lot of extra stuff you’re asking them to do.

Remo Panaccione, MD, FRCPC: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right to your inbox. I am sure you will see the folks in front of you on future programs. With that, thank you very much.

Transcript edited for clarity.