Gil Y. Melmed, MD, on the New Wave: Anti-Interleukins in IBD

Dr Melmed reviews his presentation from the Advances in Inflammatory Bowel Diseases regional meeting on interleukin-12/23 and -23 inhibitors for the treatment of Crohn disease and ulcerative colitis.

Gil Y, Melmed, MD, is director of Inflammatory Bowel Disease Clinical Research and codirector of the Clinical Inflammatory Bowel Disease program at Cedars-Sinai Medical Center in Los Angeles, California.

TRANSCRIPT:

Hi, I'm Dr. Gil Melmed from Cedars-Sinai Medical Center in Los Angeles, and I had the privilege of presenting at the AIBD Regional event. And what we talked about was the new wave of interleukin inhibitors, specifically, the IL-23 and the now new selective IL-23 inhibitor class of therapies for both Crohn's disease and ulcerative colitis. And what we've seen and what we've learned over the last number of years is that this is an extraordinarily safe and effective class of therapies.

With the introduction of ustekinumab several years ago for Crohn's disease, and then subsequently ulcerative colitis, what we saw was that in both anti-TNF exposed as well as anti-TNF naive patients, this is an effective and safe class of therapy. Ustekinumab has an extraordinarily favorable safety profile, with no specific signals seen in long-term safety data over placebo, as well as what we've learned from the psoriasis registries, for which many patients have been followed over extended periods of time, again showing no significant increased risk of serious infections and no significant increased risk relative to other classes of therapies.

With respect to ustekinumab positioning for both Crohn's disease and ulcerative colitis, it is effective as a first-line agent as well as effective after failure of anti-TNF and, potentially, other advanced therapies. We also talked about some of the distinctions between ustekinumab and IL-23 inhibitor and the newer IL-23 selective inhibitors, specifically risankizumab, which, as at the time of this recording, is approved for Crohn's disease, but also recognizing that risankizumab, as well as mirikizumab and guselkumab, or other IL-23 inhibitors that are likely to see approval for both Crohn's and/or ulcerative colitis in the near future.

And the distinction between these IL-23 ustekinumab and the IL-23 selective inhibitors may be due to a mechanistic difference that highlights the specificity of blockading just the IL-23 pathway, which may confer efficacy advantages over blockade of two pathways of the IL-23. And we've actually seen those efficacy advantages in psoriasis. We will be learning about whether or not that we truly see those efficacy advantages in Crohn's and ulcerative colitis over the course of the coming years, based on clinical trial and real-world evidence.

But what we've learned so far is that IL-23 inhibition seems to be an extraordinarily effective and also safe class of medications. The data that we've seen from risankizumab, as well as emerging data with other agents in this class, suggests that this is a highly effective treatment with respect to treatment of both Crohn's disease as well as for ulcerative colitis. With respect to safety, we are not seeing any new safety signals, with respect to this class, relative to the IL-23 class, again, which itself has been shown to be very, very safe.

One question that arises is whether patients previously exposed to ustekinumab will have response rates to the IL-23 selective inhibitors. And what we've seen, at least so far, is that patients previously exposed to ustekinumab still seem to have a similar degree of response to a selective agent IL-23 inhibition risankizumab as compared to patients who were not previously exposed to ustekinumab. This suggests that we shouldn't be thinking about this family of medications all as a homogeneous ubiquitous class, but rather that there may be differences and distinctions between these entities, such that patients who fail one may still be eligible to receive another.

Ultimately, the question of positioning which patient should receive which drug at what time will ultimately be, hopefully, clarified as we learn more about the practical use of these therapies in specific patient populations. But what we've seen so far is the efficacy of these agents in patients who are both naive and previously exposed to anti-TNF drugs.

Thank you very much for your attention. It's been a wonderful opportunity to discuss these therapies, as well as placing them in context of other medications, as we learned so much about inflammatory bowel disease at the AIBD Regional conference.