Marla Dubinsky, MD, and Asher Kornbluth, MD, on Managing IBD in the Era of COVID-19

Marla Dubinsky, MD, and Asher Kornbluth, MD, discuss their first-hand experience in treating patients with inflammatory bowel disease as New York City became one of the first hot spots for COVID-19, how they and their patients managed the transition to telehealth visits and concerns about immunosuppressive therapy, and what they have learned throughout this pandemic.

Marla Dubinsky, MD, is codirector of the Susan and Leonard Feinstein IBD Clinical Center at the Icahn School of Medicine at Mt. Sinai in New York City. Asher Kornbluth, MD, is clinical professor of medicine in the Inflammatory Bowel Disease Center at the Henry D. Janowitz Division of Gastroenterology, Mount Sinai School of Medicine, in New York City.

Transcript:

Hello, I'm Dr. Marla Dubinsky from the Icahn School of Medicine. I'm joined today by one of my closest colleagues, Dr. Asher Kornbluth. Today, our goal is to talk about our experience and our learnings of managing COVID in patients with IBD, and I couldn't think of a better person to be talking about this topic than Asher. I would have to say — and he reminds me—that he has the highest population of patients who were COVID positive and patients with IBD. 

What I wanted to do in this timely discussion is most of us are preparing for the next wave whilst at the same time people are taking about vaccine. I just wanted to set the audience straight a little bit on tell me what you learnt in that real-time lab as you were managing COVID and IBD in March, April, May and until today? And is there something that you did then that you wouldn't do now, or are there things you can help us understand how to prepare? 

Dr Asher Kornbluth: That's a great question because it's more timely sitting here. This is probably going to come out November, and this is going to be going to November, December because what we experienced in New York, which was truly a tsunami of a disaster for all of our residents here in New York and the Tri-state area is, unfortunately, coming to everywhere around the country.

It's going to sweep unfortunately, tragically to your communities as well. What I will say is this, let's assume that -- this will basically describe what we went through March, April, and May -- and assume that God willing you will see a lesser version of this, is that you'll see fewer patients in the office, they won’t travel as we will go into telemedicine. I'm sure at this moment we're all very comfortable using telemedicine whether we love doing it or not. More visits will go back to telemedicine if we had  transformed our practices to  do more live. There will be more patients at home.

What I found was during March and April, where we had a March-April pandemic peak plan, these patients only came in for really urgent visits, namely bowel obstruction or abscess, is basically what it came down to. As around the country everybody nearly shut down their endoscopy centers, and for the most part, have nearly been at full capacity now.

The only patients we brought in for procedures  were basically a stricture dilatation, looking at  perianal disease— which again those probably we sent straight to the colorectal surgeon to save them a visit. This was an infrequent patient. We went way back to the old days, if you want to know how someone's doing, you say, "How you doing?"

When we made changes, even major changes, changing to a new biologic, starting a biologic,  if the patient was quite sick, generally, we did it on clinical judgment. If it was a major call — is this a patient who might be headed for hospitalization, is this patient we’re not sure about, we would  bring them in for a quick flex sig. That was basically it.

We weren't doing any dysplasia screening, we weren't looking for post-op recurrences. We weren't looking for documenting mucosal healing after induction. It was basically stricture dilatation and if we needed  it  for real major clinical decision making. That was our endoscopy center.

The office, and what you might have to do is head back to telemedicine. Most patients and most practices are not IBD, so you're not going to be overrun with it. What we found very helpful, and the patients do have heightened anxiety, and we had heightened anxiety because we worried about our staff frankly, not so much ourselves ----we were doing infusions at our office. One of the three of us and my PA, Jim George, Michelle Hunt, one of us, or inevitably more than one, was in the office because we had patients coming in for infusions.

It's interesting, the official recommendations that have come out through a bunch of societies, the CCF, IOIBD, basically came down to the same recommendation in terms of continuing infusions outside of the home. They universally said keep doing them outside of the home  . First of all, you don't know about the nurse coming into the house, is how secure they are. More importantly, they're on a steady course.  Noncompliance, this is the time that it would happen. People drop out of their infusions, and with the usual precautions we kept -- thank God we didn't have any COVID occurring in the office while maintaining super hypervigilance during that period.

What we found very useful is we would use a blast email, and basically give them an update as to what was happening and saying the best place for daily information, whenever changes, go to ccf.org. I don't know who authors them, but I give them a world of credit. For us, there's a professional page, as well as patient education page, and it's invaluable.

The main question that comes up -- and this is again addressed by the ccf.org page and on the IOIBD page, ioibd.org -- is what to do with the biologics. To summarize a very long list of recommendations, it’s pretty simple. If they don't have COVID, then you continue all their meds except for prednisone,  and try very hard to taper them. If they are on any kind of biologics or infusion, keep them on that. Don't try and go from an IV infusion to sub-q and hope that it works. Stay on your meds. If you do get COVID, then we generally hold the medications. That was a universal recommendation. Then the big question is when to restart them.

Even though guidelines came out, I think there, you really have to use your judgment. You have to weigh against how sick was the patient IBD-wise, how important was their biologic to them, versus how severe was their COVID. If they had a fever and some sniffles for three days, wait three days for no fevers. Give them their scheduled dose if they are ready for it. On the other hand, if the patient was nearly hospitalized, or they're on home O₂ or looking at the ICU for 3 weeks and they come out of the hospital, and  they're ready for their anti-TNF, and they’re afebrile for 3 days, that's not a patient we would start. We would hold that drug. You weigh the need for the biologic versus the severity of the COVID. The patient in that middle ground, it depends on the clinical judgment.

Dr Dubinsky:  One of the things, as you mentioned already, is the avoidance of steroids. People get confused and say, "But I thought the RECOVERY trial said that you should be giving steroids." Granted it's Decadron, but my question to you is what were you doing with patients like an acute severe UC patient who are on steroids? You want to keep them out of the ED? How did you manage that acute severe UC patient? I feel it was something gave me a lot of anxiety.

Dr Kornbluth:  It's a great question. Patients, when you start decreasing their prednisone, they'll say, "Gee, I've read all about this new treatment---a medication that has been around forever, dexamethasone. It's a major change."

This gives me an opportunity to plug the SECURE registry started by Mike Kappelman and one of our former fellows, Ryan Ungaro (Marla knows what a superstar he is already). This is an incredible treasure trove of information. It's updated all the time. You could go to the site The patients can go to the site

I don't know the exact website, but if you put in "Secure IBD," it'll come to that site (it’s COVIDIBD.org)There's a bunch of tabs on the top. There's a lot of information. Go to “Our Data”. It is updated weekly. They've already published two papers. The first one is in press. I'm not sure it came out in hard copy by now. It might've. The first author, I believe -- I'm not sure -- is Kappelman.

Dr Dubinsky:  Brenner.

Dr Kornbluth:  Brenner from UNC. Just search on Brenner and Ungaro. The second paper just came out online with  Ungaro as the first author. The message is the same. Obviously, as the registry has large number of patients, the sample size gets larger, the statistics get cleaner and the confidence intervals tighter, but the message is absolutely the same.

These are patients who had IBD and developed COVID. The information is the following. Now there's 2800 patients. It looks like the way  it looked at 500 patients. The three independent variables in the multivariate analysis that stand out is in terms of a bad outcome are very simply defined. They designed this database, and I encourage you to enter your patients into that ---specifically, you could complete an entire entry in under 5 minutes. This doesn't ask you exactly how many milligrams, exactly how many months on meds or how many surgeries.

It basically just asks you to judge the patient mild, moderate, severe by your own criteria and asks you for age, comorbidities, meds, and hospitalization, ventilation, death. A bad outcome was a composite of hospitalization, ventilation, and death.

That's not that subject to subjective management. What stands out on the multivariate analysis is not that different than registries outside of IBD— the elderly had a higher rate of bad outcomes, patients with at least two comorbidities, and prednisone. And that was probably the worst player. This number changes somewhat, but for the patient on prednisone the hazard ratio is about 6 to 8 times as likely to have hospitalization, ventilator, or death. Now patients will ask about that. The definition of prednisone was was that  they were on at 20 milligrams a day, at least when they came in and developed COVID, These are patients who presumably are on prednisone for some time, in all-comers.

The dexamethasone study is waiting basically for the cytokine storm to start when they start getting sick and need oxygen and then  start dexamethasone. It's a different scenario. You want to get your patients off prednisone before they get sick enough to need dexamethasone.

The message here is an anti-TNF, in fact, reduces the likelihood of bad outcomes, and this   is consistent in the SECURE registry  from when there were 500 patients  and  now up to 2,800 patients Combination therapy, the outcomes are about the same  doesn't really reduce it doesn't really increase it. The other biologics we have, anti-IL-23, namely ustekinumab, reduces risk of bad outcome, as does vedolizumab. We emphatically don't want to stop the biologic before the patient gets sick. If they get sick we hold it and, again, we consider when to restart it.

Dr Dubinsky:  One of the interesting things to highlight, of course, the difference between Decadron and prednisone use as a marker of uncontrolled disease. And actually disease activity was also linked to saying, "I've got this already cytokine storm. I'm more vulnerable to the viral proliferation, etc."

But what's interesting is also I should note that tofacitinib, the JAK inhibitor, was also shown to have lower rates of having severe outcomes with COVID. There's even a trial of tofacitinib in non-IBD COVID-positive patients being done with the idea which you talked about.

The cytokine storm is very similar to the cytokine storm that our patients experience. Just as an anecdote, we published a paper on a 14-year-old who had been diagnosed with Crohn's 6 weeks earlier, presented with perianal abscess, drainage—again, a reason for admission at that point—COVID positive, developed the multisystem pediatric, inflammatory syndrome in children. They measured their cytokines and they had outrageously high TNF levels, IL-6, all the cytokines that we learned about during COVID.

We were debating what to do because he developed warm shock, rash, tachycardia, fever, and we gave him infliximab as a treatment to co-treat not just the Crohn's disease, but also COVID. Thankfully, that resolved his multisystem issues and he defervesced, his rash went away within 3 hours of getting infliximab.

So Mark Feldman told us in Lancet, almost a cry saying, "Why are you guys not looking at anti-TNF in COVID, as it follows the same cytokine pattern." Speaking of Pfizer, we talked about the fact that tofa has a trial, but also, as we're telling folks how to think about medication use. And I do want to add one thing—that Ryan Ungaro’s latest paper did actually look within the biologics that thiopurine mono or combination was not as protective as monotherapy TNF. In the grand scheme of it, it was an increasing COVID severity, but when you look within the TNF group, which you know how I feel about this, and anyone who's heard me speak, any reason to de-escalate a thiopurine or an immunomodulator, this may be the time.

You don't need to keep patients, maybe on steroids, and also the concomitant, maybe this is the time to think about de-escalation, if they've been on it for a while, this would be the time. I do also want to note that we still haven't figured out why mesalamine may actually worsen outcomes …I still don't understand that. I asked Ryan, if he could look at the interaction between mesalamine use and steroid use as well as disease activity, because maybe it's a marker of uncontrolled inflammation, perhaps or under- treatment.

I thank you so much for sharing your experience. People seriously benefit from knowing what boots are on the ground, what does it feel like to be managing a large population, and how our discussions are going now.

Thank you so much for sharing your thoughts. You mentioned very important websites ccf.org, IOIBD. You can look at it and see right away, how the meds you're using impact your patient.

Dr Kornbluth:  Also, they were very thorough. Maria Abreu headed up the general committee and Corey Siegel in terms of all the guidelines. They talked about guidelines in terms of infusions, guidelines in terms of endoscoping your patients, helpful tips about telemedicine, etc.

If you want all of those, it's either on the IOIBD site or the most recent — you probably are not on the mailing list of this — Journal of Crohn's and Colitis. If you go online, they have all these in a new issue. I'll give you a plug for my own article, which is basically our experience in a private practice. I am a Mount Sinai faculty, but I make my living in private practice like most of the people probably listening to this. What's it like trying to take care of patients in a private practice, managing a private practice. What we learned, and it's in the IBD Journal.

I don't write anywhere near as much as Marla. If you put Kornbluth in PubMed, it'll come up at the top of the list. You don't have to go through 900 papers.

Dr Dubinsky:  COVIDIBD.org is the website. Again, your article is game-changing and highlights that emotional aspect of what we all went through in New York. Thank you for sharing that.

Thank you to our audience for tuning in and hearing what we had to say. Hopefully, this will help you better manage your patients over these difficult times. Thank you.