Dr Horst discusses her review of available biologic therapeutics and their application in both Crohn disease and ulcerative colitis from the Crohn's & Colitis Congress 2022.

Sara Horst, MD, is a gastroenterologist from Vanderbilt University Medical Center in Nashville, Tennessee.

TRANSCRIPT:

Sara Horst:  Hi, I'm Sara Horst, a gastroenterologist at Vanderbilt University Medical Center, and I specialize in the care of patients with inflammatory bowel disease.

This year I gave a talk at Crohn's and Colitis Congress about positioning biologics in inflammatory bowel disease. This was a really exciting talk to give. It's fun to think about how many new biologics we have now and how many are coming. I suspect this talk will be much different in 3 to 5 years. I'm interested to see how that will look.

With my talk, I talked about what we have available currently in biologics for inflammatory bowel disease. The classes we have are anti-tumor necrosis factor therapy, anti-integrin therapy, with vedolizumab, and anti-IL-12/33 receptor antagonists, with ustekinumab.

I went through the data as far as efficacy, which in phased clinical trials, although apples to oranges, are pretty similar between the classes with little differences, especially if patients had been on an anti-TNF before. Unfortunately, efficacy seems to decrease.

Then we looked at what head-to-head clinical trials are available and then also looked at some real-world retrospective data in the form of the VICTORY Consortium for UC and Crohn's, and then the EVOLVE study, which is a retrospective international cohort study looking at bio-naive patients.

Then we looked at network meta-analysis data, which tries to put all phased clinical trials together and tier out what would be the best medication to give to your patients with inflammatory bowel disease.

We looked at ulcerative colitis first. Looking at anti-TNF medications, it was great to see in the network meta-analysis that this still has the best first-line induction of remission data. In the AGA Technical Review, they really emphasize that infliximab probably works better than adalimumab, and that vedolizumab probably also works better than adalimumab. In thinking about anti-TNFs in ulcerative colitis, I would likely pick infliximab first.

The other thing I highlighted is that when you're thinking about starting an anti-TNF, one of the things you need to remember is the formation of antidrug antibodies can happen in up to a third of patients. So when you're thinking about anti-TNF, you need to be thinking about combination therapy. Or if you're going to try monotherapy, if you have access to drug levels, even considering incorporating that into your practice if you're going to be using that medication. When you talk about risks and benefits of these drugs, infliximab and an immunomodulator may be what is needed.

We then looked at vedolizumab. This has great safety data in some real-world analyses, better than anti-TNF as far as lower rates of serious adverse events and infection rates. In the head-to-head clinical trial that I talked about, the VARSITY study, vedolizumab had improved clinical remission and endoscopic healing rates over adalimumab. So this may be a great option for bio-naive ulcerative colitis patients and something that I reach for frequently.

Then thinking about ustekinumab, this may be a first-line option biologic as well. I think we have a little less data on this, especially real-world, so that is something to consider. In the network meta-analysis, it did show that ustekinumab may be best if a patient's been anti-TNF exposed. So this may be a second-line medication to think about for ulcerative colitis.

We then focused on Crohn's disease and positioning biologics. Then looking at the available data, especially in the network meta-analysis, infliximab and adalimumab really had great data for first-line induction of remission. All of the anti-TNFs in Crohn's disease seem to have similar responses in large groups.

There was also a head-to-head clinical trial looking at adalimumab compared to ustekinumab, the SEAVUE study. The great news about this—and these were bio-naive patients, both monotherapy with adalimumab and ustekinumab and short duration of disease, so median duration, was about 3 years. In these groups of patients, both ustekinumab and adalimumab had great rates of clinical remission, so this is a great drug to think about. It also works very well for extraintestinal manifestations and has robust safety data in pregnancy.

In Crohn's disease, it does seem like anti-TNF probably is still something that's going to work very well in a lot of our patients. Especially fistulizing disease, or if there's been evidence of stricturing disease.

Again, remember, when you're thinking about anti-TNF, whether or not to use that immunomodulator is going to be important since we know that it has improved clinical outcomes and lower risk of antidrug antibody.

Looking at vedolizumab, there was good safety data. In some of the real-world retrospective cohort studies it may have improved safety over anti-TNF. It might be best in that bio-naive patient who has inflammatory disease only, not a history of stricturing or fistulizing disease and really has a normal albumin. When I think about vedolizumab and its positioning, it may be best in a bio-naive patient with inflammatory-only Crohn's disease.

Then in looking at ustekinumab, it had great head-to-head high remission rates when you compared it to adalimumab, especially in that bio-naive patient with Crohn's disease. It may be a great option for someone who is new, has a short duration of disease, because we are not going to have to use that immunomodulator. It has a great safety profile and it might be something that I might choose for that inflammatory-only bio-naive patient with Crohn's disease. We have a little less data about stricturing and fistulizing nature of Crohn's disease and ustekinumab. Although there is some small data showing improvement in perianal fistulizing disease in the phase clinical trials with ustekinumab. Again, no need for immunomodulator therapy.

In conclusion, when we think about patients with inflammatory bowel disease, a large number of patients will still have a good response and clinical remission rates with anti-TNF. There are some patients that might do very well with other biologics that are not anti-TNF.

When thinking about vedolizumab, especially someone who is bio-naive with ulcerative colitis, and there may be certain populations of Crohn's disease patients that might do well as well. With ustekinumab, they had very good head-to-head clinical trial response rates comparative to adalimumab in bio-naive, short-duration Crohn's disease. Again, that inflammatory type Crohn's disease patient may do very well with is ustekinumab and also may be best for anti-TNF exposed patients.

It's so exciting to see how many treatment options we have on the landscape and also what data will come in the future for us to continue to gain knowledge to see how we should position these in the future. Thank you.