Biologic Therapies for the Treatment of IBD

Stephen Hanauer, MD: You can you distinguish the different biologic therapies based on that concept of rapidity and durability? You’ve already mentioned that you believe that TNF [tumor necrosis factor] inhibitors, and most agree, we use infliximab in our hospitalized patients, and some of these subq [subcutaneous] alternatives, adalimumab or golimumab, for moderate to severe outpatients. But where do you position in your mind ustekinumab or vedolizumab at the present time?

Marla Dubinsky, MD: I’ll add that speed is relevant, as you noted, and in hospitalized patients, we have a go-to. But I would also add that in the UC [ulcerative colitis] space and maybe in the future for Crohn disease, the JAK kinase class, tofacitinib for us right now, also has a rapid onset. You published that, granted it wasn’t part of their regulatory secondary outcomes.

Stephen Hanauer, MD: It was based on your observation.

Marla Dubinsky, MD: It’s the speed. It was the fact that at 3 days you already had, over the weekend, the patient could feel better. It has happened. The reality is that speed of onset is also driven by the sequence. If you take the anti-TNF–naive patients and expose them to ustekinumab and vedolizumab, and I’m going to talk about UC for a second, they show that already at 2 weeks there’s separation from placebo. But ancestrally, the way we used to speak, is that it took so much longer for, for example, vedolizumab, and that was because we were using it in 3 TNF-refractory patients and expecting it to miraculously change the lives of the patient overnight. It just wasn’t reality. Part of it is us understanding that naive patients, that’s the more moderate patient where you have a lot of options, where you’re not rushed for speed, all of these therapies do very well, and within 2 weeks you’re going to see an effect. Now, it won’t be as big as it will be at 6 weeks or at the start of maintenance, per se, but you’re already going to see it in particularly the TNF-naive patient. That’s my impression about it. Sequence will matter as to how quickly my patients will get better, and it does differ between Crohn disease and UC. I don’t know if you feel the same way.

Stephen Hanauer, MD: I feel the same way, but in our practice, as I mentioned, it’s hard to get away from initiating a patient who’s in the clinic in front of you on some steroids while they are waiting for approval. That gives us some flexibility because they’re going to get better quickly for the most part, on steroids. Then you have the longer term to taper them off, as the biologic or other alternative therapy is becoming much more effective over time.

Marla Dubinsky, MD: I think you’re right.

Stephen Hanauer, MD: The best example of this, as you alluded to, is infliximab in the patient with severe ulcerative colitis. Because we do have clinical trials that have demonstrated that patients are out of the hospital in essentially a clinical remission within a week after IV [intravenous] infliximab in severe ulcerative colitis. We can, as you’ve alluded, to have a more rapid, active agent for this. I also agree, as we’ve said, it’s probably going to be infliximab as a TNF inhibitor.

Marla Dubinsky, MD: I wanted to add that one of things that resonated with what you said was the time factor. Do you have time? Meaning, are your steroids working as a bridge to something? I do want to echo that and make that point to the viewers because if you have a steroid-refractory patient, you have a different approach than if you have a steroid-responsive or steroid-dependent patient. That is an important point that you were making. That does speak to the rapidity but adding a layer of, did they respond to steroids or not? I 100% agree with that concept.

Transcript Edited for Clarity