Video
Ustekinumab and Vedolizumab in Patients With Crohn Disease
Edward Loftus Jr, MD, and William Sandborn, MD, review the 5-year remission data from the IM-UNITI trial for ustekinumab and post hoc analysis from the GEMINI 2 trial for vedolizumab in patients with Crohn disease.
Remo Panaccione, MD, FRCPC: Let’s get into some of the newer data that were presented at DDW [Digestive Disease Week]. Ed, you mentioned this subgroup analysis of the GEMINI [2] trial and symptomatic improvement. Do you want to summarize what [the abstract of] Marla C. Dubinsky’s, MD, demonstrated and how it may influence your practice?
Edward Loftus Jr, MD: It showed the patient with that moderate disease where the CDAI [Crohn's Disease Activity Index] is elevated, but below 330, as opposed to severe, where it’s above 330—those patients had bigger improvements on vedolizumab. They had bigger improvements in their abdominal pain scores and stool frequency scores compared with patients who had higher CDAI levels. Similarly, when they broke out anti-TNF [tumor necrosis factor] exposure, anti-TNF-naive patients had bigger reductions in abdominal pain scores and stool frequency scores than the patients who were bio-exposed. It fits with what we’ve been talking about, that there may be a window of opportunity for the patient with moderate Crohn who is bio-naive. It gives you another treatment option, where you’re not necessarily, say, relegated to adalimumab or ustekinumab, for example.
Remo Panaccione, MD, FRCPC: People who are listening may think about using vedolizumab more as a first-line treatment for Crohn disease. We had more data, Bill, that you presented as far as the long-term safety for ustekinumab. We’re always looking for more data when it comes to safety. Can you summarize what that showed?
William Sandborn, MD: Over 5 years,it showed that there’s a robust safety signal for ustekinumab. That fits with more than 10 years of data in the psoriasis setting with some of the registries that occurred there. There are no real signals for infection, malignancy, or major cardiovascular events. All those things that we worry about, to some degree, with JAK [Janus kinase] inhibitors and TNF blockers, we just don’t see.
Remo Panaccione, MD, FRCPC: The data set is very robust. I still get questions from some of our colleagues: “Well, why is that the case?” Why do you think it looks so clean? Not only as an IL-12/23 blocker, but even the anti-P19s look clean. Is it that we should accept the data, or do people need to understand why we think there isn’t a lot of toxicity with blocking these pathways? Because if we would’ve gone back to—let’s think the CERTIFY trial going into the [IM]-UNITI trial—a lot of us thought there might be a toxicity penalty, especially with higher doses, but we’ve never seen that. Do you have an opinion on that?
William Sandborn, MD: Yes; I’m a huge fan of basic science for identifying mechanisms, pathways, and new drugs, but to predict what is going to be safe from an infection standpoint, you have to go to the clinic. We have this huge amount of observed data, both observational registry data and randomized clinical trials relative to placebo, that show that IL-12/23 blockade and IL-23 blockade look like background disease. There seems to be no increase over the placebo for a given patient population adjusted for age and other factors. Conversely, that is not the case with JAK inhibitors and TNF blockers. With both of those classes of drugs, you see a higher risk of infection. With JAK inhibitors, you see a higher risk of nonmelanoma skin cancer. For a long time, we said that you needed azathioprine or 6-MP [mercaptopurine] to get the non-Hodgkin lymphoma signal with TNF blockers. Then we had that huge study out of Denmark that showed that it’s not true. There’s about a 3-fold increased risk of lymphoma with monotherapy or with TNF blockers. If you go to combination therapy, the risk goes up to 6-fold or 7-fold. I don’t think it’s chance. I don’t think it’s under study. There’s a huge amount of experience now, and they’re just different. Do I feel we have a robust scientific explanation for why anti-TNFs in the inflammation state causes infection and some forms of malignancy and [IL]-12/23 blockade does not? I don’t know, but I feel confident with this huge, amassed clinical experience with the drugs. There are differences, and I’m not waiting for another shoe to drop. We know the toxicity profile of the drug is not going to change.
Remo Panaccione, MD, FRCPC: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right to your inbox. I am sure you will see the folks in front of you on future programs. With that, thank you very much.
Transcript edited for clarity.
