Switching Between Biologics in Inflammatory Bowel Disease

Transcript:

Miguel Regueiro, MD: Doug, to summarize, for very sick patients with UC [ulcerative colitis][MB1] and Crohn disease with multiple segments and fistula, it may be that the combination approach is still reasonable, and we may use first-line infliximab with either thiopurine or methotrexate, especially in young men.

For the patients with more of a single-segment Crohn disease or the more moderate ulcerative colitis, you have some options, and whether it’s a subcutaneous anti–TNF [tumor necrosis factor] agent or vedolizumab, and maybe ustekinumab and tofacitinib play a role, especially with ulcerative colitis. Finally, age is something we didn’t talk about very much. I’m always sensitive to bring this up, but there are data that patients over the age of 60 may see increased rates of infection and malignancy to some degree but infection certainly, so we may use vedolizumab and ustekinumab, but I’ll still use anti-TNFs in combination with thiopurines or methotrexate if I think that’s the best combination for somebody.

Jean-Fred, I’m going to ask 1 question about switching again to clarify a few things, then I want to end with a discussion about COVID-19 [coronavirus disease 2019], medicines, and what you’re telling your patients. In terms of switching, how do you decide when to switch therapies as well as how to sequence therapies? Depending on what the first agent is, how do you decide to switch? What should the second agents be? When do you switch and how do you decide?

Jean-Frederic Colombel, MD: First, I completely agree with you. We should never switch for nonmedical reasons. We have the switch study showing that this is a bad idea when they were switching from infliximab to adalimumab. There are very bad outcomes, so we should switch only for good reasons. I am switching first when there is an adverse effect. For instance, if the patient has an adverse effect and can’t tolerate the drug anymore, it’s a good reason for switching.

Then I may switch if I have a problem with efficacy, and it is always based on objective criteria. This is an important point: We must be certain that the patient is not responding based on clinical data but also objective data such as endoscopy. Then we often use biologics. I look at the levels, and to me this is the main indication. You then have the different scenarios. If you have good levels and no antibodies or low levels and no antibodies, then the patient is always immunized.

For instance, let’s take the case of a patient who is not responding anymore objectively. He has good levels, meaning that you know that you can’t push anymore. You then need to switch. Let’s go with that scenario: Find some patient with a UC who is not doing well on a high dose of anti-TNF therapy, so you need to switch. The question is what should the next agent be? This is where we are missing a lot of data because we don’t have many head-to-head studies. We need to rely on indirect data: like network analysis and real-world data, but what I would be doing in those patients is this: I would most likely switch to ustekinumab or tofacitinib, for instance, because there is a different mechanism of action.

It depends on the patient’s age, their risk of adverse effects, and their preference for an oral drug or not, but based on the network meta-analysis, it looks like in the UC patients failing anti-TNF therapy, you get better results with Stelara [ustekinumab] and tofacitinib. That is based on efficacy data and indirect comparison data. Then I’m pretty sure you are accumulating those patients who have failed everything medically. I want to say something: The patient has often failed for bad reasons. You have this patient coming to your office with a 10-year history, then you see he has been exposed to infliximab and then stopped.

When you are trying to go back, why did you stop? It is often not for a good reason. They have sometimes stopped because they were fed up with the drug. You sometimes don’t really know why they stopped. Something I do, and I’m pretty sure you do it as well, is this: When you have exhausted everything that works, you go back to the history of the patient.

You can sometimes recycle treatments unless the patient had a very severe adverse reaction. For instance, when on anti-TNF therapy, then I will not recycle, but you always need to be cautious because it is often the mechanism. How the patient got this stamp of being refractory is sometimes not based on strong data, so you need to be cautious because we don’t have many drugs. This is what I would do. It’s logical: When you have good levels with a drug, you can’t optimize it further, so you need to switch the mechanism of action.

Miguel Regueiro, MD: It sounds like all 3 of us practice similarly. There are 2 important take-home points that you mentioned, Jean-Fred. To me, the most important point in time for biologics—and maybe small molecule but certainly with 1 of the monoclonals—is the induction phase. If we get induction right, if we achieve healing, whether it is in Crohn disease or ulcerative colitis, we’re usually able to enter into a maintenance phase successfully.

If we don’t get induction right, that’s when we see this sometimes in our colleagues or our people who may not be as experienced with IBD where the switch will occur quickly before optimization or before achieving that induction. That’s 1 point I wanted to make. The other is this: I’ve done this in my practice as well. As you say, for these patients who fail or have been through everything, you go back and they say that it’s usually because it’s historical: “20 years ago, I did phenomenally well with infliximab for 7 years.” “Why did you stop it?” “I can’t remember.” They didn’t have a bad reaction. Something new came out, so they switched. The days are gone where we can’t go back. We should go back, and I agree. The 1 caveat I’ll make is that sometimes in those patients, after their first infusion of infliximab after years, I may within a couple of weeks get a level—not because I want to see the level, but because I want to see if they’re forming high antibodies. If they produce antibodies after that first dose after a long period off the agent, that matters.

Jean-Frederic Colombel, MD: I fully agree. I would do exactly the same thing.

Transcript Edited for Clarity