Stephen Hanauer, MD, on Stopping or De-escalating Therapy for Patients With IBD

In this video, Dr. Hanauer, one of the cochairs of the AIBD 2020 virtual meeting, discusses his presentation on when and how to de-escalate or even stop medical therapy for patients with inflammatory bowel disease.

Stephen Hanauer, MD, is the Clifford Joseph Barborka Professor of Medicine in gastroenterology and hepatology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois.

TRANSCRIPT

Hello, I'm Steve Hanauer from Northwestern University in Chicago. At this year's Advances in Inflammatory Bowel Disease virtual meeting, I'm going to be discussing stopping or de-escalating therapy for patients in remission.

This topic is one of the most frequently asked by our patients who always want to know when they can stop or reduce their medications. I always point out that both ulcerative colitis and Crohn's disease are chronic conditions, very similar to high blood pressure. Once we control high blood pressure, we actually don't stop therapy. It's very similar in Crohn's disease and in ulcerative colitis.

In addition to thinking of individual therapies, there are also advantages, or at least potential advantages, of combination therapy. Part of the question of stopping or de-escalating is reducing from 1 therapy or from 2 therapies down to 1.

From the onset, there are a number of potential advantages of combination therapy. These include two different mechanisms attacking the disease, the prevention of immunogenicity when immunomodulators are added to biologics, increased drug concentrations of the biologics.

As well, there are a number of potential disadvantages, including a potential for increased side effects of dual therapy and the complexity and the cost of the individual regimen.

Nevertheless, and at this year's American College of Gastroenterology meeting, we see continued data on the advantage of adding an immunomodulatory agent to a biologic, and in particular we're talking about TNF inhibitors in this situation.

There is less evidence for utility of combination therapy with ustekinumab or itolizumab to this point. We currently advocate combination therapy for patients initiating TNF inhibitors, in particular for those who are going to be on infliximab.

We advocate continuing the therapy for at least 6 to 12 months before reassessing the patients. We would never consider de-escalating therapy unless a patient is in a complete biologic remission, meaning symptom-free, no biomarkers of inflammation, and normalized endoscopy.

At the same time, there are a number of individuals who are less good candidates or poor candidates for combination therapy. This includes young male teenagers who are at risk for hepatosplenic T-cell lymphoma or complications of Epstein-Barr virus.

In addition, we're less likely to advocate combination therapy for patients who are older than 65 because of the risk of complications, including infections and lymphomas in the older age group.

When we consider stopping therapy at all, it's important to remember that even in the setting of the deepest remission, which would be a surgical resection with re-anastomosis of 2 healthy pieces of bowel, there is a near-inevitable recurrence of the disease, in particular of Crohn's disease.

When we consider stopping therapy, there are 4 possible scenarios. If a patient is on a biologic, stop that. If they're on an immunomodulator, stop that. If they're on combination therapy with a biologic and an immunomodulator, stopping the immunomodulator, or if they're on combination therapy, stopping the TNF agent.

All of these have been investigated to some extent. We know that biologics are necessary as maintenance agents, so stopping them will inevitably lead to flare-ups. Likewise, stopping immunomodulators have been associated with an increased risk of flaring up.

On the other hand, patients who are on combination therapy may be able to stop either the immunomodulator or the TNF inhibitor if, as I've already mentioned, the patient is in a deep remission with no evidence of inflammatory symptoms, elevations of biomarkers, or a normalized colonoscopy with absence of ulcerations.

If any of those situations don't hold, there is a much greater risk of relapsing when stopping any of these individual agents. The other good news is we can restart a biologic agent if the patient has had a hiatus as long as the patient is receiving concomitant immunomodulation and is usually pretreated, at least for first several infusions with corticosteroids to prevent against the small likelihood of a allergic or a delayed hypersensitivity reaction.

There are a number of caveats on restarting tumor necrosis factor agents. Absence of prior immunogenicity and, as I've already mentioned, predosing with immunomodulators and steroids for at least the first several infusions.

A practical approach to stopping is making certain we have the right patient, who's at low risk for recurrence, confirming a stable, deep remission, confirming adequate drug levels of which drug we're going to continue if we are stopping one or the other, and then continuing to reassess the patient along the way in our treat-to-target strategies, confirming a continued maintenance of remission.

Those are the topics that I'm going to be talking about in a little bit more detail, but I hope I've given you some insights into who and how and when we may stop or reduce combination therapy in the setting of inflammatory bowel disease.