Drs Regueiro and Siegel review their debate from the Advances in Inflammatory Bowel DIseases 2022 annual meeting about if, when, and how to stop or de-escalate therapy for IBD.

Miguel Regueiro, MD, is chair of the Digestive Disease & Surgery Institute at Cleveland Clinic in Cleveland, Ohio. Corey Siegel, MD, is the section chief of Gastroenterology and Hepatology and the codirector of the Inflammatory Bowel Disease (IBD) Center at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire.

TRANSCRIPT:

Dr. Miguel Regueiro:

I'm Dr. Miguel Regueiro. I'm professor and chair of Digestive Disease and Surgery Institute at Cleveland Clinic in Cleveland, Ohio.

Dr. Corey Siegel:

And I'm Corey Siegel, section chief of Gastroenterology and Hepatology at the Dartmouth Hitchcock Medical Center in New Hampshire.

Dr. Regueiro: So Corey and I have made a tradition at AIBD of doing a debate, and we've had a fun time with this. It usually follows a case-related session and we have a lot of banter back and forth. The audience seems to really enjoy it. We dig at each other a little bit. So I think it's very much in good fun. And this year we debated whether we could stop therapy or not, and I had the side of stopping therapy, specifically TNF, and Corey took the side of not stopping therapy. And at the end of the day, as many of these debates go, we actually agree more than we disagree.

So the data I looked at were the SPARE study, the STOP-IT study, the STORY study, which just briefly put, are all studies that looked at de-escalating off of TNF inhibitor therapy. And each of them showed basically the same thing, that about 50% of people will relapse within about 2 years, 70 to 80% within about 5 years, which means about 20 to 30% that do not. But I think the other important message of this is that you could stop the anti-TNF and then restart it successfully and regain that response. And now we even have other therapies. So Corey, I know you took the other side, but maybe you can say what you thought.

Dr. Siegel:  You mean the right side.

Dr. Regueiro:  Since I am sitting on your left, yes.

Dr. Siegel:  So I mean the idea of stopping anti-TNF therapy used to be crazy a decade ago or even 5 years ago, when we only had a few other choices. Stopping a therapy that was working wasn't something we would even consider. But we do have fairly reasonable data now, 2 trials that showed us that it is reasonable to stop anti-TNF therapy when you're on a thiopurine or methotrexate at the same time, because a relatively large number of flare in those first couple of years, up to 50%. But you could recapture most of them when you restart anti-TNF therapy, as long as you have this background thiopurine as it was studied, probably methotrexate going, so that you're protected against antibodies forming when you restart it.

So it's not wrong that you can't stop therapy. The trouble is if you do well for the first year or 2 or flare and restart it, you're probably okay. But if it goes a little bit longer than that and even 3, 4, or 5 years, the chance of successfully restarting it dramatically drops. And as we joked about in the debate that we're not just talking about short-term patient care here. Say of a clinical trial, 1 or 2 years is fine, but we're thinking about the lifetime of a patient with inflammatory bowel disease. So really stopping therapy when someone's doing well is not encouraged and something that we really try not to do. Now with that said, there are circumstances where it might come up and make sense. Maybe you can comment on when you would think about, oh, we can use these data for good and help us manage patients.

Dr. Regueiro: So I think some of it's the practical reality of patients move, they lose their insurance, their insurance changes, there's somewhat of a forced stop. I think there are other circumstances where a patient develops an adverse event or has something happen and they have to hold therapy. And as you said, it's not something we generally intend on doing, nor do our patients. I mean, I think you've done a nice job at showing patients actually want to stay on, especially their biologic. But in those cases where they have to stop, I think there's some comfort knowing that especially in those patients in deep remission, they can successfully do so. And as you said, they can then restart at some point in the future.

Dr. Siegel: Let me summarize where I think we came to together as a consensus, and then let me pose one more scenario to you, and I'm curious to hear what you have to say. But the consensus we came at was if you're on a biologic drug and it's working, you should probably stay on it. And there are some scenarios where you might have to stop it for the reasons you mentioned, whether it's financial, an adverse event, that's different. But electively stopping a drug that's working without adverse events is not encouraged in almost all scenarios.

So with that said, we didn't talk about the other biologic drugs. So what would you think about drugs that have a much lower immunogenicity like the IL-12,12/23s, or vedolizumab and the others in that class that are coming?

Dr. Regueiro: No, I think that's a good question. And you could even take it a step further and say the oral small molecules, which again is a whole other consideration. I agree with you that if a patient's doing well, we're not stopping their therapy, independent of the biologic, independent of the small molecule. But your point's well taken, and I think there are two aspects to this.

One is, with these very low immunogenicity medications, ustekinumab, risankizumab, vedolizumab, and with the oral small molecules, it does lend the ability to stop the therapy and restart it. Again, not recommending that, but that's something we can do. The other thing that I would throw out there is if you're on a TNF, and this is something that we're stopping the TNF, it also doesn't mean the patient has to go back on the TNF, even though that is what I would initially recommend. We now have all these other options. So if we do stop one, a TNF, we have the option of restarting with another at some point in the future.

Dr. Siegel: No, I agree. One of the scenarios a colleague came up afterwards to ask a question about—how would you handle this scenario? And I'll give my answer and then I'm curious about yours. The scenario was patient felt amazing on infliximab. It changed their life. They felt great. Moved, lost insurance, went off it for a few years, thought they were doing fine, and then reflared and said, "Can I please go back on infliximab?" And he said, "How would you do it? What would you do? "

So the recommendation I gave was I would start a second drug and in this case a thiopurine or methotrexate, probably give that 4 to 6 weeks to kind of get going while you're getting your prior authorizations ready and schedules for reinduction. And the way I do it, and there's really not great literature to support this one way or the other, is I give a dose to start and then 2 weeks later I check an antibody level. I specifically send it to Prometheus Labs because that's the only lab that really can reliably give us an antibody result that we understand when they're circulating drug.

If there is antibody present, I usually stop at that point. If there's no antibody, I'll give a second dose, but I don't give it at week 2. I give it at week 4 and then a third dose at week 8. And there actually is one study that shows lower immunogenicity with reinduction at 0, 4 and 8 than 0, 2, and 6. So that's what I do. But I'm curious if you do something differently.

Dr. Regueiro: Exact same thing. I won't even repeat it because I do the exact same thing. The only thing I had done in the past that I don't do now is I used to also automatically premedicate with steroids. I would give IV hydrocortisone, but I don't do that anymore.

Dr. Siegel: I used to do it all the time and now it's slowly going away. And the data that came, I think where you had trained, at Beth Israel Deaconess if I remember, even they say they don't do that anymore. So while we do it and maybe it makes ourselves feel better, maybe it does prevent some infusion reactions. I don't know that it has the ability to prevent antibodies from forming.

Dr. Regueiro: And there's a burden of steroids, too, when we do that, obviously.

Dr. Siegel: Great. Well thanks Miguel. I always enjoy the debates. I hope the audience learned something during the debate and from this video.

Dr. Regueiro: Yeah, we didn't beat each other up too badly this year, so it was fun and hopefully we'll have to come up with something next year.

Dr. Siegel: Excellent.