Dr Loftus reviews his Presidental Poster Award-winning presentation on results from the phase 3 ADVANCE and MOTIVATE studies of risankizumab therapy among patients with Crohn disease. 

Edward Loftus, MD, is a professor of medicine at the Mayo Clinic in Rochester, Minnesota.

TRANSCRIPT:

Hi, I'm Ed Loftus. I'm a professor of medicine at Mayo Clinic in Rochester, Minnesota. I wanted to talk to you today about one of the posters that was presented at ACG.

This one was an endoscopic analysis of the induction studies of risankizumab in moderate-to-severe Crohn's disease. Recall that risankizumab is an anti-IL-23 monoclonal antibody.

This was studied in two large phase 3 induction studies. One was called ADVANCE, and the other one was called MOTIVATE. They had similar trial design, but the study population was slightly different.

The trial design was that patients were randomized to 1 of 2 doses of risankizumab or placebo, and they were given IV-induction at weeks 0, 4, and 8, and then assessed at week 12.

The difference was that, in one of the studies, the patients were basically all bio-exposed. Then the other study, it was a mixture of bio-naive and bio-exposed patients. To be precise, I shouldn't say bio-naive and bio-exposed. They either had failed or were intolerant to a biologic or they were not intolerant or had failed a biologic.

Recall that the primary endpoint was...Well, it was a coprimary endpoint of a clinical endpoint, which in US was a CDAI score of less than 150, and in Europe was a PRO score because the differences in the regulatory agencies.

The other coprimary endpoint was an endoscopic endpoint. We're going to dive into more deeply the endoscopic endpoints in this trial.

If you look at the results in the trial that the demographics were similar within each trial amongst the 3 treatment groups, the difference being that, in the ADVANCE study, we had patients who were a mix of having failed a biologic or not having failed biologic. These patients had shorter disease duration. They had less corticosteroid use, less modulator use, etc.

In MOTIVATE, this was all bio-failures. We saw more baseline corticosteroid use and, obviously, by definition, more biologic failure. Basically, everyone had failed at least 1 biologic. Let's talk about the endpoints.

The main endpoint was endoscopic remission, and this was defined as an SES-CD score of less than or equal to 4, and at least a 2-point reduction from baseline, and no subscore of greater than 1 for any of the 4 parameters of the SES-CD.

The overall results were positive for both doses of risankizumab. There was about a 15 to 16% treatment difference in the ADVANCE study.

In the MOTIVATE study, there was roughly a 15 to 16% difference for endoscopy, and for endoscopic remission at week 12 in a Crohn's trial, that's impressive. Very strong results.

Then for another endpoint defined as ulcer-free endoscopy, and I'd like to think of this as our old definition of mucosal healing. This means the ulcerated surface subscore had to be 0 among patients, where that ulcerated surface subscore was at least 1 at baseline.

They had to have an erosion at baseline, and there were no erosions or ulcers at week 12. Again, for this endpoint, for both doses of risankizumab in both trials, this was positive. We're talking about a 9 to 14% difference in the ADVANCE trial, and about a 9 to 11% difference in the MOTIVATE trial.

Then if you start combining the clinical endpoint of CDAI response, which is a 100-point decrease with the endoscopic response, which is a reduction of 50% in the SES-CD, you again see positivity for both doses in both trials.

That ranges anywhere from 17 to 24% in the ADVANCE trial, and roughly 15 to 18% in the MOTIVATE trial.

What this is telling us is that we're not just seeing clinical improvement, we're seeing endoscopic remission and such with this drug at week 12, which again for Crohn's disease, is impressive. Overall, very exciting. A promising therapy for Crohn's disease. Thank you.