Dr Kane reviews her presentation at the ACG Postgraduate Meeting. on accurately diagnosing moderate, severe, or refractory Crohn's disease, and the many treatment options now available for these patients.

Sunanda Kane, MD, is a professor of medicine at the Mayo Clinic in Rochester, Minnesota.

TRANSCRIPT:

Hey, Suzy Kane here from Mayo Clinic in Rochester, Minnesota, professor of Medicine at the IBD Center there. I am at the annual conference for the American College of Gastroenterology in Vancouver, Canada and the postgraduate course kicked off with an IBD session and I was honored enough to present the very first presentation of that section. And I was tasked to speak on moderate, severe, and refractory Crohn's disease using data and evidence to make treatment decisions. And so what did that really mean?

So first of all, I started off with some context for why we thought the patient wasn't responding. Did they really have refractory disease or were we trying to treat a different condition? So did the patient have an infection that we were missing, or are we overtreating IBD and we should be treating irritable bowel syndrome, or do we have the wrong medication for that patient, or is the patient really in need of an operation and not more medicine, or are we not able to actually optimize the therapy that we have them on? And that's where we get the pushback from insurance companies and the frustrations of having data, but not necessarily being able to use it.

So in that context, as clinicians, what can we do to make sure that our patients are actually getting optimized therapy? So I did present some data to show that there are differences for patients who are male versus female in terms of anti-TNF therapy. And that it seems to be, if you look at all of the experience from the registration trials, patients whose sex is male actually have a much better chance of having a clinical response and mucosal healing than if you were born with a female sex. And that's very intriguing and it really sort of speaks to the differences of hormones and the immune system in general between the sexes. And then we talked about where we were in terms of the anti-TNF failures. What do you give them next?

We have data for ustekinumab versus vedolizumab as second line because we have that choice. And I presented the data from two different studies, one was from the UK and one was from Italy, to show that there were no differences in between the outcomes for patients, whether it was 3 months or whether it was 12 months or 52 weeks between giving people either ustekinumab or vedolizumab. So it didn't matter which one you chose next. So basically we are forced to use anti-TNFs first. Second line, either an Anti-interleukin or an anti-integrin. Well, what do you do after that? Okay, now we have small molecules, oral small molecules. I never thought in my career that we would be able to use oral therapy that was an immunomodulator that wasn't steroids to treat IBD, and here we are treating Crohn's with upadacitinib and we don't have fistula data yet, but that for sure upadacitinib is a very effective molecule for active Crohn's disease.

I presented some late breaking data on guselkumab versus ustekinumab for Crohn's disease and showed that they were similar for any outcome that you looked at, whether it was clinical remission, mucosal healing, or patient related outcomes. And so the question then becomes is there an advantage to targeted anti-interleukin? Because that's what guselkumab is and that is what risankizumab is. Ustekinumab, that's interleukin 12 and 23. Maybe you only need the anti-23 and maybe you only need one of those subunits. So now we are really drilling down to the exact target that needs to be addressed. So this is really interesting that perhaps these global types of therapies are not necessary anymore. And so that story is evolving.

And then I sort of finished up with the fact that we still need surgeons. Surgeons are really important for when a patient has a fibrostenotic stricture that is causing obstruction. There might be a small inflammatory component to that stricture, but if it is predominantly fibrostenotic then that patient needs an operation and it's post-op that you have to decide what medical therapy is appropriate for them to prevent another surgery in the patient's lifetime. But don't forget about your surgical colleagues.

And then just in summary, I made sure that people understood that whichever trial you were looking at for Crohn's disease, that anything is better than placebo, so that any dose of the therapies that we have available to us are at least 50%, if not 60% or 70% better than placebo. So that's important to keep in mind. Number two is that we are very excited about the oral small molecules and that the indications for labeling are such that perhaps we can be using them before the biologics. And that is really an eyeopener because we always talked about how biologics are the game changer and now we're trying to shift that ship and maybe that we should be using targeted small molecules before the biologics and seeing how patients do.

And then it all comes down to individualizing treatments for the patient that's in front of you. This is not cookbook medicine. And that there were questions and concerns about a young woman who has bad IBD and giving her a nontargeted JAK kinase. You're not giving her enough credit to be making the decision for her about her reproductive choices and health. And having a discussion about the safety during pregnancy is an important discussion, but don't make assumptions about your female patients and withhold therapy and therapeutic choices just because they have a uterus. That patient may never use it or certainly isn't going to use it in the next 6 to 8 months. So don't pick a therapy because of the pregnancy safety if she hasn't specifically said, "I want to be pregnant." So again, this is not cookbook medicine. We have an armamentarium now full of different therapies, different mechanisms of action, and that only with time are we going to understand the sequence and the positioning of each of these for specific patient phenotypes.