Optimizing Treatment Strategies to Manage Inflammatory Bowel Disease - Episode 8

IBD Treatment: Approach in Moderate- to High-Risk Disease

September 10, 2021
Remo Panaccione, MD, FRCPC

,
William Sandborn, MD

,
Jessica Allegretti, MD, MPH

Expert gastroenterologists share their perspectives regarding overall treatment approach in a patient with moderate- to high-risk inflammatory bowel disease.

Remo Panaccione, MD, FRCPC: Bill, let’s go to the other side. The other extreme is our patients with higher risk, moderate to severe disease. We touched on this already about what drugs you will use when treating those individual patients but can you start painting some patient profiles for the audience on where you would maybe use 1 drug versus the other, broadly? I would be surprised if I would go and see you at UCSD [University of California, San Diego] and you’d say, “Every patient with moderate to severe Crohn’s disease patient gets drug X.” There must be some nuances here. What is your approach to treating patients with moderate to severe—say, let’s start with this—Crohn’s [disease]?

William Sandborn, MD: Well, I think in Crohn’s disease, what makes it definitely an anti-TNF [tumor necrosis factor] therapy? It would be the presence of a fistulizing disease, especially perianal disease and arthritis. I do not think any of the other drugs designed to treat Crohn’s cover arthritis well so those entities are definitely going to be a TNF blocker. As you pointed out, if you are going to give a TNF blocker, you need to do it right, so it should be in combination therapy with either a thiopurine or Methotrexate, for patients who are probably middle aged, or in young adulthood. But for patients beyond the early 20s and middle age, we use more thiopurines. We use them because they are more proven in terms of the synergy on the extremes of age. So for teenagers or seniors, we use Methotrexate. There is some level with seniors, or I might just go with monotherapy because of the safety issues of combination therapy. The preponderance of patients, if you are going to give a TNF blocker in my opinion, should have combo therapy. Then you have this moderate, uncomplicated Crohn’s disease. I think monotherapy with vedolizumab [Entyvio] works well in those patients as Ed just pointed out, and then you have patients who have failed with 1 or more biologics. In my way of thinking, unequivocally, the best treatment for those patients is used for them. If you have the p19s, they may be even better when they use anti-interleukin 23 antibodies, as those eventually come into the clinic.

Then you have dermatologic manifestations, like pyoderma gangrenosum, andI think you can treat with the TNF blocker, but in my experience, ustekinumab [Stelara] works great for that as well. For drug-induced psoriasis, ustekinumab works well. It is approved for the treatment of arthritis. I do not think it is as good as a TNF blocker, but it will work in some cases of arthritis. It is not a strong player in the phase 3 clinical trials, in axial arthritis, and closing spondylitis were negative. It plays out like that as we get JAK1 [Janus kinase 1] inhibitors in Crohn’s. That will be a contender for patients who have failed to improve with other methods of treatment and also for arthritis, so that’ll be interesting. Then, for ulcerative colitis [UC], again, for the moderate patient without complications, vedolizumab is safe. It is a great drug. If you are in the hospital or very nearly in the hospital, they are probably using only 1 drug: infliximab [Remicade]. If you are using it in combination with azathioprine [Azasan], if you have failed 1 or more biologics—the network meta-analysis, comparative data, and then just the primary outcome measures of the population of patients who failed—these suggest that tofacitinib [Xeljanz] and ustekinumab have generally similar efficacy, and ustekinumab is quite a bit safer. So I am going to use 1 of those 2 drugs and potentially prefer ustekinumab because of the safety. Those are some broad generalities. There are caveats to all of that, but I would be interested to hear what Jessica and Ed are doing. This gets the heart of the matter; what do you really do?

Remo Panaccione, MD, FRCPC: Jessica, is there anything that you heard Bill say that you disagree with, or is that generally how you practice?

Jessica Allegretti, MD, MPH: No, I would say something very similar. Unlike some of my Boston colleagues, I still use a lot of combination therapy. I very much believe in that as well. I tend to use a lot of Methotrexate in my practice, though. I think it is because I do see a lot of young people, but regardless, I would say I think about Crohn’s and UC very differently. I think, again, I have concern for a worsening prognosis in my patients with Crohn’s. They could have fistulizing disease or stricturing disease, which tends to happen a lot in my practice. I look for any of those prognostic signs that we talked about. I am very quick to start a TNF in combination with an immunomodulator; that tends to be my first-line treatment unless the patient really has—that other patient we were just talking about had more mild disease—just still has some smoldering moderate disease.

Most of the time, I am starting with the TNF in combination for my patients with Crohn’s, unless there is really a compelling reason not to. In the treatment of UC, as I mentioned, I really like starting with vedolizumab. That is my first-line agent of choice for somebody who has failed 5 ASAs [acetylsalicylic acid], for example, and really has proven that they need biologic therapy. We have a very hard time getting ustekinumab as a first-line treatment, despite it being approved as a first-line therapy for UC in our region. While there are definitely scenarios when I would like to use ustekinumab as a first line treatment, it is very hard for me to do so. That is where I tend to start with for my UC patients, but again, to Bill’s point, I do take into consideration the order of things, because it does matter in terms of what you are going to be able to do next. I think you do have to be really thoughtful about this upfront. Again, you want to try to get it right the first time, so you must be taking all the patient characteristics, the phenotype, their prognosis, and prognostic factors into account and try to make the most informed decision possible, but that’s generally how I tease things out.

Remo Panaccione, MD, FRCPC: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our eNewsletters 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.

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