Inflammatory Bowel Disease Treatment Selection



Miguel Regueiro, MD: I'm going to ask you, Marla first and then Jess, this same question in terms of how you look at the overall deciding or positioning biologics, response, remission, but also safety profile. Then, Bill and Dave, I'm going to switch to how you consider switching therapy, getting into if you've been on an anti-TNF [tumor necrosis factor] first, what next? Marla, how do you position? How do you take into account efficacy and safety?

Marla C. Dubinsky, MD: I'm going to revert back to that thought process on speed to help frame the way that I approach IBD [inflammatory bowel disease] in terms of my treatment choice. For small bowel disease, anti–tumor necrosis factor therapy is still my go-to in anyone with more than a short segment of small bowel, ileocecal deep ulcers. I still have a lot of confidence in the mucosal healing data that we have from anti-TNF, so I still start to stratify. If there's long-segment small-bowel disease, I choose a TNF over ustekinumab and over vedolizumab; I'm talking for Crohn disease for a minute. I would have to add, for someone with pancolitis who's got low albumin, who's got high CRP [C-reactive protein], I'm also choosing anti-TNF. It gets into the concept that I'm looking for: the more severe patient, using disease location as a driver as well as burden of inflammation.

I will say that, in a patient with more moderate disease, I tell my patients everything is on the table. If I take Crohn disease, say a patient with more moderate, 15 cm Crohn disease, I start to talk to them: “Which one do you want to go with?”

It's one thing for us to sequence. Patients have their own ideas, based on how long a drug's been on market, for example. That does come into account in decision-making. If they know somebody who's been on the therapy and had an [adverse] effect, that changes how you're approaching. I first classify location and severity in my thought process.

For patients with more moderate UC [ulcerative colitis], I tell them I would prefer to use ustekinumab or vedolizumab over infliximab just because sequence matters, potentially more so with vedolizumab than with ustekinumab, meaning if you fail TNF, vedolizumab, especially for Crohn disease, and for UC, it does not seem to carry as much weight. Ustekinumab looks like in UC, it's as tofacitinib: it is not completely agnostic to TNF failure, but you do better even if you've seen an anti-TNF compared to vedolizumab. Sequence matters in terms of what they have seen, which I know Bill and Dave will talk about.

I wanted to add a plug. With perianal disease, I'm going with an anti-TNF. That's it. That's a direct phenotype that I know, for people with extensive small bowel disease, capsule-showing ulcers that are all over, I'm going with anti-TNF. I’m using segments. Patients with a lot of extraintestinal manifestation, arthropathy is the most common one.

As someone else noted, ustekinumab is not approved for rheumatoid arthritis. Why? Because it's missing the IL-23 [interleukin-23] receptor variant. Therefore, targeting IL-23 was not going to be very helpful in rheumatoid arthritis. I’m segmenting age; I want to highlight that since I manage both pediatrics and adults. Bill was noting that, on the extreme ages, we would avoid combination therapy, and most of my patients would fall into those extreme ages. We [at the Icahn School of Medicine at Mount Sinai] would use a lot of optimized monotherapy of TNF, if we weren't using a combination, especially thiopurine. We may use methotrexate instead, but we're using a lot of monotherapy in kids, especially tied to EBV [Epstein-Barr virus], and most kids are EBV naïve when we're starting all of these therapies, so that does come into play. I also wanted to add on growth failure for pediatric patients; the only therapy to date that has really shown an impact on growth has been anti-TNF. We don't have phase 3 or we don't have approval for vedolizumab or ustekinumab in pediatrics, so I can't say with as much strength about the growth aspect, but our belief is that growth failure is a type of extraintestinal manifestation. Therefore, you need to outside of the gut to attack the growth plates, and we do have data to support that anti-TNF does target it. Does that help frame where my thinking is?

Miguel Regueiro, MD: You get into a lot of good aspects in terms of the perianal disease, the anti-TNFs. You're looking at extraintestinal and, as a pediatrician, the growth failure and anti-TNFs. Then, for that single segment, not as severe, ustekinumab/vedolizumab. That sets it up nicely, Jessica, to ask you the question in terms of safety and toxicity. Marla touched on that a little bit, but Marla talked about the efficacy positioning based on predictors and certain features that we see. How do you consider different ages, cancers, infections? How do you do that in terms of positioning your therapy?

Jessica R. Allegretti, MD, MPH: I'll piggyback off what Marla said in that I agree with a lot of what she was just discussing. You have to think through those high-risk patients like we've already been talking about. For high-risk patients, I'm still using anti-TNFs. That's the best available therapy we have. That being said, when I have a patient sitting in front of me, I take that into account, and I treat a lot of older patients. I've got several elderly patients on my panel who are on biologic therapy.

You have to take into consideration not only their disease classification, their risk factors for their IBD specifically, but also their comorbidities as we've been discussing. Do they have a personal history of cancer? Are they being actively treated for cancer and what type? Is it solid organ or liquid tumors? Do they have heart failure? There are many; MS [multiple sclerosis], as we also alluded to. As our patients get older, we have patients with several other comorbidities that we have to keep in mind when we're thinking about therapeutic choices, clotting disorders being another.

When I'm laying out options for my patients, I take into consideration 3 major factors: speed of onset, how the therapy is administered, and the safety profile. Then, you have to find the sweet spot of the combination of those 3 things that is right for that particular patient. In my patients, as you were just getting at, Miguel, patients with cancer histories or for higher-risk patients, I would preferentially be using things like Entyvio [vedolizumab] or ustekinumab in those patients because of the safety profiles of those agents. I've got several elderly patients where I'm more inclined to start with something like Entyvio or ustekinumab than infliximab, if I can.

If their disease is quite severe and you don't have other choices, you do what you have to do, and you treat their disease. I work closely with many of my oncology colleagues, and many of them will tell you: do what you have to do. If you have to treat, and you need to use an anti-TNF, many of them are completely fine with that. I take all those things into consideration.

Miguel Regueiro, MD: Use your best therapy to induce remission but take into account factors. The final summary from what you just said, Jessica, is that monotherapy vedolizumab, monotherapy ustekinumab, seem to be safe in terms of our comparison to anti-TNFs and certainly anti-TNFs with thiopurine. That's a good take-home point as well.

Transcript Edited for Clarity

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