Dr Rubin recaps his presentation from the ACG scientific meeting on the results of phase 3 trials of guselkumab for treatment of Crohn's disease among patients who are bionaive, bioexposed, and biointolerant or who failed to respond to biologics. 

David Rubin, MD, is the Joseph B Kirsner Professor In Medicine, chief of Gastroenterology, Hepatology and Nutrition, and director of the Inflammatory Bowel Disease Center at the University of Chicago School of Medicine.

Hi, it's David Rubin from the University of Chicago and I'm in Philadelphia at the American College of Gastroenterology annual meeting and it's 2024. I have the honor of presenting on behalf of my coauthors the results of the week 48 efficacy of guselkumab and ustekinumab in patients with moderate to severe Crohn's disease as the analysis of those based on those who are bioexposed, biointolerant or failure patients and bionaive patients and part of the GALAXI 2 and GALAXI 3 phase 3 trials.

Now as a reminder, guselkumab is a P19 antibody, which also has a component that binds something called CD64, which is related to where IL-23 is made, and this therapy has previously demonstrated superiority over placebo in patients with moderate to severe Crohn's disease, and it's also already available on the US market approved by the FDA for moderate to severe ulcerative colitis.

The GALAXI 2 and GALAXI 3 trials were identically designed treat-through studies in which patients were randomized to receive either guselkumab IV, followed by maintenance dosing of 200 milligrams sub-Q every 4 weeks, or maintenance dosing 100 milligrams sub-Q every 8 weeks. They were also randomized to an arm that received ustekinumab with a standard IV loading single dose and then 90 milligrams every 8 weeks sub -Q or placebo. Now we've known the previous results that guselkumab was superior to placebo and actually was superior ustekinumab. In this analysis we look at whether patients who were bionaive or those who were biofailure, biointolerant were going to respond differently and whether they were superior to ustekinumab.

The results at week 48 demonstrate overall that whether patients were bioexposed and failed those therapies or were intolerant to them, and whether they were bionaive, they were superior with guselkumab over ustekinumab. When you break it down, though, the results demonstrate statistical superiority for the endoscopic endpoints and then when looking at the individual breakdown by the different subgroups of biofailure and biointolerant versus bionaive, there was numerical benefits across the board. Because of the statistical design, they didn't do P values, but it's clear to see the deltas that there's a benefit across the endoscopic endpoints.

When looking at the clinical endpoint of clinical remission, which is, of course, a symptomatic endpoint based on the CDAI, it's interesting to note that there's, of course, higher symptomatic improvement than we see with endoscopic results, which is very common in our Crohn's studies, but that there's not a significant difference overall between clinical remission in guselkumab and the ustekinumab arm. Obviously, superiority against placebo was previously shown.

When you break it down further, though, you can see some numerical benefits of guselkumab over ustekinumab. And when you look specifically at combination endpoints of endoscopic response or endoscopic remission with the clinical endpoints, you then again see the statistical benefit overall. And the breakdown demonstrates some clear benefit of the guselkumab arms. And the 200 milligram every 4 weeks seems to be best in some of the bioIR patients—those who were failing biological therapies or intolerant to them.                                    

So the overall results of this important analysis demonstrates some additional messages. One is that whether your patient is bionaive or whether they have already been on biological therapies that didn't work or they were intolerant to, guselkumab appears overall to be superior to ustekinumab by endoscopic measures of endpoints, which we accept as objective measures, and by the combined clinical and endoscopic measures. But the clinical results look similar, again emphasizing the importance of knowing the difference between symptoms and disease management with objective measures of disease control.

I think these results are really quite important and add to our evolving understanding of this new therapy for our patients with Crohn's disease. Thank you.