Millie Long, MD, on the Potential of Interleukin Inhibitors in IBD

Dr Long discusses her presentation at the Advances in Inflammatory Bowel Diseases regional meeting in Baltimore on the use of interleukin-12/23 and -23 inhibitors in the treatment of IBD.

Millie Long, MD, is a professor of medicine, vice chief of education and director of the fellowship program in the Division of Gastroenterology and Hepatology at the University of North Carolina at Chapel Hill.

TRANSCRIPT:

Millie Long:

Hi, this is Millie Long from University of North Carolina and I'm here today to give you an update on a recent presentation from the AIBD Baltimore Regional where I discussed the role of interleukin inhibitors in the treatment of inflammatory bowel disease. So we have not only an IL-12/23 inhibitor, but also a novel IL-23/p19 inhibitor that's approved for the treatment of Crohn's disease. So let me start with the IL-12/-23 ustekinumab, which is approved for both Crohn's disease and ulcerative colitis. And we have a lot of great data surrounding not only the efficacy but also the durability of this therapy. We really have low immunogenicity. Patients don't get antibodies to this therapy at the same rates as they do to medicines like anti-TNFs. And in fact, the rate of immunogenicity is around 2%, so quite low.

So these therapies can be used alone in monotherapy because of that also enhances the safety. Efficacy wise, effective not only for ulcerative colitis, but also in Crohn's disease. From an ulcerative colitis standpoint, there are great data on IL-12/23 inhibitors as being more effective after the use of TNFs as well as in primary bio-naive populations. And so this is a nice therapy for both of those. I will say from a safety perspective, there have been recent data out of DDW last year that really talked about malignancy risk. And so we have robust data combining both the psoriasis and the inflammatory bowel disease populations that really show no increased risk of malignancy of any type, including no increased risk of non-melanoma skin cancer, which has been seen with other immunosuppressive therapies in the management of IBD. The new kid on the block is the anti-IL-23/p19, risankizumab, has been approved for the treatment of Crohn's disease and this drug is also quite safe, quite effective, quite durable.

And when you look specifically at the data that brought risankizumab to market, what we see is that the drug has a great long-lasting effect, that same durability. What we don't know yet is how it will do in individuals who've previously been exposed to IL-12/23s. We did review some data from the psoriasis literature that actually showed that IL-23s are superior to IL-12/23s. And when you look in the data from the registry trials for risankizumab, there was a small segment of the population that had previously failed ustekinumab, and those patients did seem to have response and remission rates at a similar rate to other populations, individuals who had not yet failed an IL-12/23. So this gives us hope that this drug may be even more effective. Time will tell, and I think further real world data are needed.

So these drugs can be used either as first line advanced therapy or certainly as second line advanced therapy post-TNF. And again, the risankizumab data where actually quite robust in terms of not only induction but maintenance of remission even in that previous biologic failure population.

The other thing I'll mention is that this class of drugs seems to do very well for skin manifestations. So in particular, psoriasis. So if you have a patient who has had a prior TNF-induced psoriasis, these classes will just melt that away. These neutrophilic dermatoses, really quite excellent drug for treating that as well as the underlying inflammatory bowel disease. So I hope some of these data surrounding efficacy, surrounding durability, use in pre-TNF populations as well as post will help you as you think about sequencing and which drugs are right for which patients.

I'm excited to see some of the novel IL-23/p19s that may be coming soon to market. We did review data on both mirikizumab as well as guselkumab, which are additional anti-IL-23/p19s currently in late stage clinical trials for inflammatory bowel disease, both Crohn's disease and ulcerative colitis. So I hope, and I suspect, that those may be in our arsenal down the road. So with that, hopefully you can use these tips and this information to help to treat your patients and position agents in the management of IBD.