麻豆传媒

A study presented at the recent Digestive Disease Week (DDW) virtual meeting looked at discontinuing infliximab (Remicade) in patients with Crohn's disease, and found that there was a considerable risk for relapse despite the fact that this group of patients were in complete remission going into the trial.

In this third of four exclusive roundtable episodes, 麻豆传媒 has brought together three expert leaders in the field: moderator , of Baylor College of Medicine, is joined by , of Michigan Medicine, and , of Yale School of Medicine, to address what this study might answer for the very common patient question: "How long do I need to stay on therapy?"

Episode one: Do COVID-19 Vaccines Protect IBD Patients?

Episode two: Biologic Therapies for Crohn's Go Head-to-Head at DDW

Following is a transcript of their remarks:

Jason K. Hou, MD: Hello, everybody. I am Dr. Jason Hou. I am an associate professor of gastroenterology at Baylor College of Medicine. I'd like to welcome you to the DDW Virtual Roundtable on 麻豆传媒. We're really fortunate to be joined by two panelists here today: Dr. Shirley Cohen-Mekelburg, she's an assistant professor at the University of Michigan, as well as Dr. Jill Gaidos, associate professor at Yale University.

All right. The abstract I'd like to discuss or bring up for conversation was a very interesting abstract. It addresses a very common comment or question patients have for us about, "How long do I need to stay on therapy?" -- how long especially when referring to biologics.

This was an abstract that was presented. It was a titled "Discontinuation of infliximab therapy in patients with Crohn's disease in sustained, complete clinical-biochemical-endoscopic remission: A double-blinded, placebo-controlled, randomized clinical trial."

This trial again was addressing an important question that we get a lot. For patients who are doing well who are in remission -- and this was, I think, added the rigor of patients who were in endoscopic and radiographic biochemical remission, and randomized to continue on their infliximab versus go on placebo -- how would these patients do?

In this study, they found that about 50% of patients flared by the end of the trial. So what is your take-away points or comments from the abstract, from the study, and how do you incorporate that into what you tell your patients when they ask you this question?

Jill Gaidos, MD: I think, like you said, it's a very common question that we see in clinic. Patients want to know, "Do I have to be on this forever? At some point, will I be able to come off of this medicine and be on nothing?" I think with the STORI trial we were under the impression that patients who were in endoscopic remission had a better chance, or at least a longer duration, where they may not relapse. But I think with this study we now know that doesn't ... it's not protective. There really is still a very high chance of relapse when coming off of therapy, so it's nice to have a randomized study, a much more rigorous study, where we can say, "We looked at this and your chance is still 50% of relapsing in 1 year."

Shirley Cohen-Mekelburg, MD: One of the things I actually really like about this study is that patients with IBD [inflammatory bowel disease] are a heterogeneous group of people. You have patients who have moderate disease, you have patients who have severe disease, you have patients who have fistulas, and those who've undergone surgery. I actually really like that they stratified their randomization both by fistulizing disease and also by concomitant immunosuppressants, and so I think that was kind of a great thing to make sure they accounted for.

I think, as you all are saying, the findings were not necessarily unexpected. I think what is interesting here, though, is that 50% of patients did do well after stopping their infliximab, and kind of the Holy Grail is if we can identify who those folks are. I think there really is a knowledge gap here that this study really is the beginning to that investigation.

I think it is great that the patients who were included in this trial were those who were in endoscopic remission. I think it's interesting that they didn't necessarily speak to histologic remission and that might be coming, let's say, in an actual manuscript.

There's been a few studies out recently, including, actually, an abstract out of University of Chicago during DDW this year that looked at all sort of colitis, not Crohn's disease. But it was a small, retrospective study, but they were able to show that histologic remission was associated with increased odds of relapse-free survival. That was not only patients with infliximab. I think a majority of those patients were actually receiving mesalamines. But I think one of the big things missing in this abstract is understanding people's histologic remission status.

Gaidos: Absolutely, and I think to this study, when they broke out the patients who were on combination therapy, I think we had previously thought, "Well, maybe we'll do combination therapy, get their disease in remission, and then they may not need the biologic anymore, and we can just kind of maintain them with the immunomodulator." But really, that group relapsed almost as quickly as those who were just on placebo, so we now can see that that is not necessarily protective for these patients either.

Cohen-Mekelburg: I always -- just to ask -- what is your current practice when it comes to de-escalation and how do you think this will change that, if at all?

Hou: The party line is that if you're doing well on your biologic, my recommendation is that you stay on the biologic. Making reference to the STORI study, as you already mentioned, Dr. Gaidos, I think this is even more supportive now, it's a more rigorous prospective randomized placebo-controlled trial, which interestingly, shows a very similar number, the 50% chance they're going to have a flare in the next year.

I thought this study, which I think looks for things that may -- interpret things with a grain of salt -- they had 0% flares in their infliximab group at 1 year, which, I wish I had 0% relapse of patients on therapy, so there may be something else.

Gaidos: I'd like to see their drug levels.

Hou: Yeah.

Gaidos: Maybe they keep them all at 50.

[LAUGHTER]

Hou: Yes. There may be some more details that we'll get out in the formal manuscript. But again, my comment to my patients is that if you're doing well on it, we talked about adjustment. De-escalation, in my mind, for when I'm doing it, and discussing with patients is if, for example, we had to escalate based on levels to get them into endoscopic remission. We'll talk about using drug levels and to deescalate them potentially down to standard dosing. But unless they have an extenuating circumstance related to adverse events, cost, access, I try my best to discuss with patients the importance and recommendation of staying on their biologic.

Gaidos: Absolutely. For me, the biggest concern too is I think patients have the mentality that they can stop these medicines and restart them. But I've had patients who did well on a thiopurine for many years, decided they wanted to stop it for a minor side effect, and then have a terrible flare where now we're going through medicines to try and get them into remission.

For me, that's the biggest concern, is we may not be able to use this medicine for you, and we may need to switch to some other IV therapy or a self-injectable that they hadn't been on before. Really, they have to really decide if they want to risk discontinuing and maybe having to get back in the hospital because we can't get their disease under control again.

Cohen-Mekelburg: Jason, you did bring up a very good point about the infliximab-treated arm having 100% remission at 1 year, and I think to some degree, it does speak to the benefits of treat to targets, like if you are in endoscopic remission at baseline you're more likely to stay there. But it also, while this is a randomized trial, does make you wonder about the selection for the study. My guess would be that if you have a patient who's a little bit tenuous, you're probably not going to recommend them for a trial of de-escalation, or at least the possibility of being de-escalated, so that probably plays into that too.

Gaidos: Yeah. Absolutely.

Hou: Yeah. Those are great points from both of you. Again, just to summarize, this was a study, again, addressing a very common question that we get from our patients, "Can I stop my biologic?"

I think this study adds, again, another tier of data on top of what we've had before saying if you stop your biologic, you have a fairly high [risk of relapse] -- I think most of us as clinicians and providers say a 50% risk of relapse in a year is high.

This is somewhat, I think, an interesting aspect of this study being randomized, a blinded placebo-controlled trial, is that we had that even with patients who, as you mentioned, Dr. Cohen, were at the start already in clinical endoscopic remission, 50% of them flared in a year when they stopped infliximab. That, to me, is high and the concern is, as Dr. Gaidos mentioned, that there is a percentage (I usually say about 10%) that maybe won't respond or have immunogenicity or only partial response when they reintroduce the biologic. That's definitely a concern.

I think it can be very helpful for us, it provides additional data for us to have this difficult conversation with our patients, and to hopefully, again, let them be aware of what the risks and benefits are of continuation versus discontinuation of their biologic when they're in clinical and endoscopic remission.

Thank you, Dr. Cohen. Thank you, Dr. Gaidos, for that great discussion. Thank you to the audience for joining us for this, and hopefully we'll see you for one of our other topics.

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