Discontinuation of Infliximab and Risk of Relapse in Patients With Sustained Complete Remission of Crohn’s Disease

PracticeUpdate: A study from the DDW conference focused on the discontinuation of infliximab in Crohn's disease. Why was this study important?

Dr. Naik: Another important study from Digestive Disease Week discussed a topic that we come across and deal with in the clinic every day in our patients with moderate to severe Crohn's disease, and frankly, also colitis as well, but we're going to focus on Crohn's disease because that's what was evaluated in this study.

And what we're seeing here is, yes, initiation of treatment, successful treatment outcomes. But then once we're better, our patients are always asking us, "Do I need to be on this therapy forever?" And for a long time, some of our tongue-in-cheek responses were that, "We hope so," because we hope it continues to work for a long period of time.

However, I think, therapy discontinuation in a subset of patients may be okay. And let's talk about this trial, but I will say this, and then we'll say it again, therapy discontinuation may be something to do, but I think monitoring for inflammation, potentially, has to increase emphasis when we stop treatments that have been proven to work in a condition that we know is long-term and we don't have a cure for.

Study Background

So that being said that, the discontinuation of infliximab was evaluated in patients who, and this is very important, sustained, so long, complete clinical biochemical endoscopic remission. So I like to call this logical remission, where any potential logical measure that you potentially could have had to look for disease activity is negative. And for not just a point in time, but a sustained point in time.

So, other studies have looked at this issue with infliximab in moderate or severe Crohn's, and it's shown rates that are 30 to 50% at one year and over 50% at two years. And then what they wanted to do is say, "Hey, can we stop infliximab in patients who are really, really not showing any signs of active Crohn's disease for a period of time?"

Study Design

So it was a placebo-controlled, multi-center trial. They had about little over 100 patients that all were on infliximab for over a year. They had luminal Crohn's, that's important. And essentially, you didn't show any signs of combined remission, which is defined as CDAIs less than 150, no endoscopic, MRI, or capsule signs of activity, normal biochemistry profiles. And they were one-to-one randomized to get either infliximab or placebo for a 48 week period. And they defined relapse, much as we would in clinic, potentially, but we use potentially CDAI, but an increase of either over 150 or increase in baseline over 70 for two consecutive weeks, or clinical relapse, which is what we would do in clinic, as judged by the treating physicians. And then they wanted to look at time to relapse and proportion of patients maintaining a combined remission.

So, roughly about close to 60 in each group, essentially, and looking at some of these time to relapse rates, and you see things deteriorating the placebo group pretty quickly, I would say. Essentially starts separating things out in that less than 100 days.

Study Findings

And so remission rates at the end of the trial, I think, strongly favored the infliximab group, both for combined and clinical endoscopic remission. I'm talking about basically 96 to 40, 50% for clinical remission, and roughly the same 90 to 30%, actually, for clinical and endoscopic remission. And so, certainly, the immunomodulators on board as well contributed favorably, increasing the time to relapse, but the infliximab group still had really clinically significant longer time to relapse, sorting out at that one year, 350, 380 day point.

And so, then the placebo and immunomodulator group. So really, demonstrating infliximab's robust clinical activity in moderate to severe Crohn's. So essentially, 50% in patients who discontinued infliximab, which was essentially the placebo group, and clinical relapse-free survival at one year, which is what we were talking about, was 100% in patients who continued infliximab, which is pretty hard to argue against.

PracticeUpdate: How does this information impact patient care?

Dr. Naik: I think what we know from this is that stopping infliximab, stopping effective therapies does carry a high risk of relapse. Even patients who are really doing well, combined clinical biochemical endoscopic remission, I would challenge you to really sort those patients out. It may not be a large portion of patients in your practice. And so, this risk is something finally we can give patients and let them know that, "Hey, we've looked at this. This is what the risk is. And this is where we're at." And I think taking into account their history, how tough it was to potentially get them into remission, and the potential available therapies and their ability to actually intensify monitoring is really important prior to initiating those discussions of stopping an effective treatment.

Certainly stopping treatments that are ineffective very appropriate, but it's also very challenging to stop things that have worked well. And I do understand there are risks and benefits and harms that come up and having that ongoing discussion is great. And more and more literature here, trying to figure this out, is important, is good as well.