Optimizing Therapies for CD

Transcript

David Hudesman, MD: Miguel brought up a great point about optimizing therapy. Millie, and this is taking away drug levels, because we could always talk all about that.

Millie Long, MD, MPH: [We could talk about] therapeutic drug monitoring all morning.

Maia Kayal, MD: This side vs that.

David Hudesman, MD: How do you make that decision? Do you think that patient is optimized? In the same line of questioning, how long do you push? Every one of these therapies has a post hoc analysis and some response within 2 or 4 weeks. Then you have patients who don’t respond during induction, and we have data on delayed responders. How do you optimize and figure out timing for that patient?

Millie Long, MD, MPH: That’s a good point, David. There isn’t 1 answer because it depends a lot on how the patient is doing. We don’t need an extended induction on everyone. If someone is truly a primary nonresponder at 12 weeks into a therapy—if they have a TNF [tumor necrosis factor], if they have a good level—then we’re changing at that point. If someone is a partial responder, for those patients I might try to do an extended induction to get them there. One key thing is that you need objective measures; it’s not just symptoms alone. You’re also checking biomarkers. You’re starting to see if there’s any down trend in this. Frankly, a lot of times, I’m restaging the patient. I’m rescoping. There are some novel data that ultrasound is a noninvasive technique, and I’m going to throw that to Maia to tell us a little more. It may help us in reassessment, but we need something objective to help us. For me, the TNF’s drug levels are what you need to help to maximize those. I don’t find drug levels as useful with the IL-12/23, IL-23, or vedolizumab. I just don’t use them in my practice. There’s such low immunogenicity that it’s not going to change what I do. But for the TNFs, it does. Whatever that level is, whatever the antibody is, it changes my practice.

Miguel Regueiro, MD: Millie said something important. I want to add 1 thing for the audience: 12 to 16 weeks is how I live with my patients with Crohn [disease]. What I mean by that is 12 to 16 weeks of induction. If they’ve had some response, we can continue, but after 12 to 16 weeks of induction, if there’s 0 response, then we move to something else. In the interval beyond induction, where they’re responding or they’ve come out of remission and they have objective disease, I try to optimize. That may mean bringing the drug closer together. If it’s a TNF, I give a higher dose, and then it’s another 12 to 16 weeks. It’s not 1 month and then switch if it’s not working. Three to 4 months is the cycle. Don’t have somebody stuck for 6 to 9 months on repeated steroids. If they’ve gone through 12 to 16 weeks and optimized therapy, and they’re still not responding, then we need to move to something else.

Maia Kayal, MD: The consensus is that you have to know whom to optimize. If a patient is having a clinical response, that’s a good patient to optimize. But if [a patient doesn’t have] primary nonresponse, don’t waste your time trying to optimize.

Millie Long, MD, MPH: It’s going to drag it out for the patient. We’re going to get more steroids. That’s not the way to go.

Maia Kayal, MD: We talk a lot about optimization. We’ve gotten good with the anti-TNF agents. We’ve gotten smarter, and we know how to use therapeutic drug monitoring to help us optimize. But if your patient isn’t responding and has never responded to the agent, don’t waste your time and optimize. Move on.

Miguel Regueiro, MD: Don’t switch too soon, but don’t wait too long.

David Hudesman, MD: That’s a great point because when you hear that certain agents might take longer to work, that’s exactly what happens. We’re seeing these patients who have been on the same therapy for 6 or 9 months—on and off budesonide, on and off steroids. Within those first 3 to 4 months, I need some signal, whether it’s clinical or a biomarker. Then I’ll keep pushing. When we’re talking about drug levels, we have some smaller studies looking at pushing a vedolizumab or ustekinumab dose. But without an initial response, you’re not going to gain anything from that. You need that signal. If you have that signal, that’s when you push and give it some time afterward.

Anita Afzali, MD: In situations with a partial response—and we’re not checking drug levels for non-TNF—if they’re having a response, this is when shortening the frequency or giving another dose even without drug levels is warranted before you’re canceling the therapy.

Transcript edited for clarity.