Drs Stephen Hanauer and Raymond Cross recap their debate from the Advances in Inflammatory Bowel Diseases annual meeting on the use of corticosteroids in managing IBD.

Stephen Hanauer, MD, is the Clifford Joseph Barborka Professor of Medicine at the Feinberg School of Medicine and medical director of the Digestive Health Center at Northwestern University in Chicago, Illinois. Raymond Cross, MD, is a professor of medicine and director of the IBD Program at the. University of Maryland School of Medicine in Baltimore,Maryland.

TRANSCRIPT:

Dr Cross: Welcome everyone to IBD Drive Time. I'm Dr Cross Cross from the University of Maryland School of Medicine. I'm delighted to have Steve Hanauer from Northwestern here to talk about steroids; never or forever? Steve, welcome to IBD Drive Time.

Dr Hanauer: Well thank you, Ray. I was just hitchhiking along the way. You picked me up. Thank you.

Dr Cross: You're welcome. So we debated at AIBD, you took the stand steroids forever, I said steroids never. And we agreed before the debate that we would always use steroids in our practice, that it wasn't going to be possible to completely eliminate them. But for the listeners, what practical advice do you have to limit steroid exposure in their patients?

Dr Hanauer: Well to begin with, we have established that patients with moderate to severe disease, be it ulcerative colitis or Crohn's, have a bad prognosis. And I like to emphasize we can diagnose moderate to severe disease at presentation. You don't need to wait for a patient to fail. So if we had access to one of the steroid-sparing agents right away, a biologic, and that could be a TNF blocker with or without an immunomodulator, it could be an antiadhesion molecule without immunomodulators, an anticytokine, either anti-IL-12/23 or an anti-23, IL-23, or one of the newer smaller molecules, the sphingosine-1-phosphate, or a JAK inhibitor at diagnosis, that would limit our steroid exposure. The problem is pragmatically, they're not accessible immediately. While they have access, it takes time to get that access. And we've got to cover the patients who are sick over that time. And that means we need to give them some steroids.

Dr Cross: Yeah, I completely agree. We were talking before a little bit about when you write for the steroid prescription, the second thought a provider should have is, "What am I going to do to keep them off of steroids in the future?" Did I get that right?

Dr Hanauer: Absolutely. As soon as you start a steroid, you better be thinking, "How am I going to get them off?" And we just went through that list of either with an immunomodulator or one of the biologics or one of the new small molecules.

Dr Cross: And oftentimes I hear gastroenterologists talk about UC patients in particular, giving them a chance of maintenance with a 5-ASA after a steroid taper. So do you think that all UC patients warrant one try at 5-ASA maintenance or does it depend?

Dr Hanauer: Well, I think it depends. If they have deep ulcers, they're going to fail 5-ASA. And that's been shown. On the other hand, there has been a comparative study of azathioprine versus 5-ASA after steroids, and azathioprine won. So I think, again, if the patients really have moderate to severe disease and in particular deep ulcers, I'm going to skip over the 5-ASAs.

Dr Cross: Yeah, I agree. What about safer steroids? So maybe we can't completely keep people off steroids, but maybe we can keep them off prednisone. So ileal release budesonide, budesonide delayed in an extended release, the MMX formulation, are we underutilizing those agents for Crohn's and UC?

Dr Hanauer: Well, when we say steroids are not maintenance drugs, it's really a lie. They are maintenance drugs. We all have steroid-dependent patients. It means that they can get better with steroids, but you just can't get them off. So I think using a safer steroid, a less systemic if possible, would be a route to doing that. But you still need to monitor for side effects. And the other thing we need to recognize is that budesonide is now in generic forms. And we need to realize that the 3-milligram form is really an ileal release for right ileal or right-sided colonic disease, whereas the 9-milligram MMX formulation is a colonic release more for ulcerative colitis.

Dr Cross: And I think that I've had a little better success in my career with the ileal release for Crohn's than the MMX for UC. But I think for the listeners it's ... I think perhaps 50% of patients will do fine on budesonide and maybe you can spare them prednisone.

Dr Hanauer: Well, it may be because your criteria of defining success. So if you're talking about improvement in symptoms with Crohn's disease versus mucosal healing or improvement with ulcerative colitis, we're really looking at slightly different endpoints.

Dr Cross: I think you and I are talking about, can we cool you off a little bit until the 2 ½ weeks it takes to get you started on your advanced therapy?

Dr Hanauer: Possibly. But if these people are really sick, I would bypass budesonide and just rapidly try for an effective steroid-sparing agent.

Dr Cross: All right. Just to remind the listeners, IBD Drive Time is sponsored by AIBD and the Gastroenterology Learning Network.

So Steve, when you give prednisone, how do you give it? What dose do you use? How long do you wait for it to take effect? When do you start tapering? How fast do you taper? I think we all do this a little differently.

Dr Hanauer: Well, there's limited evidence. There was an old study done in the 1960s or ‘70s comparing 20, 40, or 60 milligrams of prednisone in ulcerative colitis. The 40 and 60 were better than the 20 milligrams and the 60 was a little bit better than 40, but with many more side effects. In my practice, we’re usually giving about 40 milligrams. Now the AGA guidelines or ACG guidelines recommend 60 milligrams, and I can accept that. As far as tapering is concerned, in my view it's an equilateral triangle; the longer it takes for them to get my goal of remission, the longer I'm going to taper. If they achieve it right away, I'll try for a faster taper.

Dr Cross: And then when do you start tapering? So I've seen some providers, they start tapering immediately. I tell my patients, "When you've had 3 straight days of formed stool without blood for UC or you're back to baseline without pain in Crohn's, you message me and then we'll start to taper." How do you do it?

Dr Hanauer: I think that's reasonable. I think the problem is tapering too quickly. And we see this all the time in the hospitalized patient. When they're going from intravenous steroids to oral, we're going from a methylprednisolone, which is more potent milligram per milligram than prednisone, to prednisone. So if you're going from 60 milligrams of Solu-Medrol daily to 40 milligrams of prednisone, that's a big drop. If they're not already well, you're just pulling the rug out from under them. So I use the same criteria plus one. My criteria with ulcerative colitis are formed bowel movements, no blood, no urgency, and able to fart without using the toilet. It means they've regained their rectal compliance.

Dr Cross: No gas incontinence allowed.

Dr Hanauer: Correct.

Dr Cross: And I think that one mistake that I see—and I'm lucky where I live that I think our community gastroenterologists are really quite good—is you're trying to spare the patient side effects. So they'll give 20 milligrams and then they wait a little bit, and then they go up to 30 milligrams, and then they're up to 40 milligrams. And all that's happened is you've just extended the amount of time that the patient's on steroids instead of just giving them 40 out of the gate.

Dr Hanauer: And extending the area under the curve of exposure to it as well. So I agree completely. I start high. I don't give anyone intermediate doses. I start high and if they respond quickly, taper quickly. I agree with you completely on that.

Dr Cross: You mentioned the severe colitis patients that are in the hospital and guidelines are 3 days of intravenous steroids, 40 to 60 milligrams, and if you haven't responded, move on. So I think for the listeners it's clear, 3 days in the vast majority of cases is enough time to assess response. Are there any patients you skip the corticosteroids at admission and just go right to an advanced therapy like infliximab or cyclosporine?

Dr Hanauer: Well, definitely. And I'm going to shift it a little bit because that algorithm or that paradigm was 20 years ago before our biologics, actually. And now we're seeing a large proportion of patients who are admitted with severe colitis who've already had inadequate responses to biologics. And I think we're going to need to change that algorithm now. And a number of us, and I'm sure you are as well, are starting to look at JAK inhibitors as an oral therapy perhaps in these severe patients with ulcerative colitis, particularly the ones who have already had been exposed to infliximab or TNF blockers.

Dr Cross: And we were talking a little bit before about those patients that you do your sigmoidoscopy or colonoscopy and you see deep ulcers and those are the patients that should immediately, I think, go to an advanced therapy. But pragmatically, if you're talking about infliximab, as you mentioned, that you need to get ... You should get your QuantiFERON or your PPD back, you should get your hepatitis serologies back. So it does take a little bit of time anyway. So really if you're prescribing advanced therapy at 3 days, you're doing pretty good, I think.

Dr Hanauer: Yes. I think we would probably try to accelerate that. Because again, if the patient's already had a biologic, they should have already had those tests to rule out infections or hepatitis B.

Dr Cross: Right. So for the listeners, you might as well get all those tests the first time you see a patient and make sure they're all done, so then there's no diagnostic delays in really starting anything.

Dr Hanauer: Hey, as soon as they start on prednisone, they have moderate to severe disease and they're going to need one of these therapies. So that's the time to start with your testing for infections and starting to immunize them against everything.

Dr Cross: All right. So for the severe UC patient that doesn't respond to steroids, I think that we don't know exactly what to do with the steroids in that situation. So you've gone to an advanced therapy, they've responded to the advanced therapy, what do you do with the corticosteroids? Do you drop them to 40 and then continue to taper as the outpatient with the advanced therapy? Assuming they weren't on it. We're assuming they weren't on steroids before they entered the hospital, which may not really occur. But do we just stop the steroids completely or do we do a taper on those patients?

Dr Hanauer: Well I think that if they've had a very short course of steroids, we can probably just stop them. But unfortunately, we are confronted with a lot of people who've been on steroids for a long time, and in those individuals we're a little more conservative and gradually taper them. We may taper them to 10 milligrams quickly and then be a little bit slower to make certain that their adrenal gland is coming back.

Dr Cross: Agreed. We don't talk about the COMMIT study that much anymore. So for the listeners, I think most people know about SONIC and UC SUCCESS, but COMMIT was a study done by Brian Feagan where all patients were induced with steroids and then were randomized to infliximab alone or infliximab plus methotrexate. And the take-home message from that study was that combination infliximab/methotrexate is no better than infliximab alone. The message I took from that study was 2 drugs are sufficient, you don't need 3 drugs. So that using prednisone with infliximab in combination was highly effective at inducing remission. So is there a subset of ... First of all, did you interpret it that way? And secondly, is there a subset of patients we should purposely be inducing with steroids plus an advanced therapy?

Dr Hanauer: I think we need to take a step beyond that as to how you're going to manage patients on infliximab. If you're going to require combination therapy from the beginning, then you better start with the azathioprine or methotrexate as they're on steroids. If you're going to give monotherapy and therapeutic drug monitoring, which has been a major part of the discussion here at Advances this year, then you're going to need to start monitoring drug levels early.

Dr Cross: But do you think that coinduction with steroids in an advanced therapy potentially is associated with better outcomes? So should we use a little bit more steroids to get people cooled off sooner?

Dr Hanauer: I don't know.

Dr Cross: Me either.

Dr Cross: All right. Time for the fun question, Steve. Tell the listeners something about yourself. Now this is your second time on the show, so tell them something about yourself that they may not know or that I may not know.

Dr Hanauer: My memory's not good enough to tell you what I said the first time. However, I'll just mention that ... Married 50 years, three sons, seven grandchildren, and I'm very content in life.

Dr Cross: Perfect. Steve, thanks for joining us. We hope to have you back soon.

Dr Hanauer: Thank you, Ray. And by the way, I got to my destination. You can let me off here.