Novel Expert Perspectives in Treating Moderate-to-Severe Ulcerative Colitis - Episode 6

UC Treatment: Anti-integrin Antibodies and Anti-interleukins

June 14, 2022
Miguel Regueiro, MD

David P. Hudesman, MD

Ellen J. Scherl, MD

Marla Dubinsky, MD

David P. Hudesman, MD, reviews the use of anti-integrin and anti-interleukin therapies for the management of ulcerative colitis.

Miguel Regueiro, MD: Dave, I want to move beyond anti-TNFs [tumor necrosis factor]. Can you talk to us about the anti-integrin and anti-interleukins?

David P. Hudesman, MD: With all our therapies, we have a good initial response rate. As Ellen was mentioning, it may be up to 70% in certain patient populations. But even with anti-TNF, a year later, one-third or 40% could lose response. It’s great that we have multiple options for our patients. For our anti-integrins, we have vedolizumab, which is FDA approved for moderate to severe ulcerative colitis. The way I like to explain this to patients on the mechanism is that this is very targetive; it’s gut specific.

If you imagine your white blood cells as cars on the highway, each exit off the highway is a different part of your body: brain, heart, lungs, and intestine. All vedolizumab is doing is messing with the car’s GPS [global positioning system]. The white blood cells are not getting to the intestine. Because of that, from a safety perspective, as Marla was discussing, patients are concerned if it’s a safe agent with low infection adverse effects. We don’t need to worry about malignancy. It has low rates of infusion reaction. The way I present it to patients is, the biggest risk in my mind is whether it’s going to work. Is it going to be efficacious?

Then we have ustekinumab, which is an anti–IL-12 and IL-23. It blocks the p40-subunit. Originally when the mechanism came out, we were concerned about some potential infection risk, but what we’ve seen in the data and the psoriasis literature since it’s been FDA approved for psoriasis since 2009, is that it’s a targeted agent. It has a good safety profile and low infectious complications. With malignancies, that’s not a concern. When you’re talking about efficacy, and Marla Dubinsky stated this nicely earlier, patients are concerned if it’s FDA approved and if it works. We’re seeing a 60% to 70% response rate, 30% to 40% remission rate, and somewhere in between endoscopic remission rate. Those are similar across trials. We’re going to talk about more sequencing as we dive into if these are bio-naïve patients, are they exposed, and the difference vs placebo to help us position.

Miguel Regueiro, MD: The anti-integrins in the anti-interleukins take us to the next level. Both have great safety. We’ll get into positioning and sequencing in a minute. But those were the most recent 2 monoclonal antibodies.

Transcript Edited for Clarity