"Management of the Hospitalized Acute Severe UC Patient in 2022" presented by Asher Kornbluth, MD.
A virtual course series created by Dr. Jean-Frederic Colombel and his team to provide medical education on IBD management to IBD physicians practicing in Ukraine, addressing the lack of educational opportunities available as a result of the war.
Chapters (Click to go to chapter start)
Therapies in Acute Severe UC (ASUC) Indications for Surgery Systematic Review of IV Corticosteroids in Severe UC “Salvage Therapy” Infliximab vs Cyclosporine Sequential Therapy: Is it Effective and Safe to Use Acute Salvage with CSA after IFX, or Vice Versa, in Patients with IV Steroid Refractory UC? Top 10 Pearls and Pitfalls in Managing ASUC Okay so first of all I have to say thank you so much on fred for putting this together. Thank you Alex? I'm not sure how I can pronounce your name off the screen but I have to tell you I am extremely moved by this. My parents actually uh lived in the Ukraine for a sec several years many, many years ago so I have a particular allegiance to to the Ukraine and the one of the people is the most important in my life and my practice is gnarly dude who wants to say hello, She's from Ukraine, I was very lucky to recruit her, she wants to say hello also hello, how are you? Okay? I see, I mean this is maybe the first time I would expect them a doctor in the Ukraine to be smiling. This is uh I'm so happy that we could do something to make you smile. I know you guys are going through something that we should we should never have to live through um Sorry sorry I should have a problem with your. Fine, I'm really sorry, I'm trying to open thank you. What did you say? It's not popping up, can you try to share your screen again? Uh um No I don't know why it's not working, I'm sharing now. It says you're screen sharing um you want to send them to me Asher, do you want me to try? Yeah sure. Whatever works for you um just um you see I'm sending to you because I don't know how to do it. Yeah no problem, no problem but I'm already sorry maybe you stop sharing your screen and lizzie lizzie will. Okay. Okay. It's okay. Let me drop them to myself. How is he next time we should all do this live, john fred either inside Ukraine, Ukraine next time. God willing. Sometime soon. Are you able to share anything? You are a muted? Yeah, one second. I had to open the pdf but yeah, I think I can hear. Beautiful. Yes better. But I'll work on that as you start presenting. Okay. Thank you. Just mentioned next slide. Okay. Okay. Okay. Thank you Alex. And everyone watching as I just said, this is near and dear opportunity. So thank you john fred for having me. So I'm gonna speak about managing hospitalized, acute severe, you see patients in the hospital. So this is the patient who's been sick enough that we're not getting them better with steroids and typically patients who are sick enough, we've admitted these patients often after already getting inflicts a mob and I'd be, I'm fascinated to know afterwards outs and I left time for questions About your access to various medications that I'll talk about next slide. So uh and this is how we're practicing. There's nothing here that's any different than what we do here ivy steroids if you're going to use them in the dose of 300 mg survive the steroids a day. 150 mg twice a day. There's no benefit to anything higher if you have access to salvage therapy is the term we use now salvage therapy. Either cyclosporin or inflicts a mob. And if you don't have that then a sofa city nib or even had to sit in it which are pills which you think might be a little inadequate for severe colitis but might be a very effective even in the hospital's patient as we'll see I can tell you that surgery in my opinion. If you've gone as far as you are comfortable with as a gastroenterologist sending the patient for surgery is almost never the wrong thing to do. But we do have options. Besides I. V. Steroids we don't have control trial data. That doesn't mean we won't use it for use to kenya mob mob to fix it and maybe at this point will patterson and uh oh Roseanne Ahmad certainly don't have any control trial data and frankly of all of these I wouldn't depend on Roseanne Ahmad or used to kenya or frankly and tvo for someone who needs to get better in the next 24 48 72 hours next slide please. So patients who should not even think about medical therapy is patients obviously with continued hemorrhage because as you know this is not a a single ulcerated area. There's nothing we could do. An endoscopic lee if you have a toxic mega colon that's a patient for which we don't have three days or five days or seven days mega colon means it's time to think very seriously about operating and there's a day difference between mega colon and toxic mega colon and toxic colitis mega colon. You could have a sick colon that's just been very dilated. That alone is bad enough. If you have toxicity with that fever is Lucas psychosis. That patient with a dilated Colin should be in the O. R. Within 24 hours. Sepsis is obviously something we're not going to continue to treat. If the patients will come back to remake that pain should have their calling out. And very importantly, if a patient has multiple hyper koa global events, multiple from Bostic events. We think seriously about surgery. Our standard now is that every patient who comes in for surgery, certainly every patient, even who is coming in with acute severe ulcerative colitis should get DVt deep venous thrombosis prophylaxis typically with heparin sub Q five 2000 units twice a day. That's prophylaxis if they develop a robotic episode and they are high risk of robotic episodes because of a they're mostly or somewhat bed bound and two with this acute inflammatory response. There is a very significant risk of from Bostic events and even mortality. So if a patient has a throne Bostic event. Despite sub cue heparin prophylaxis will do full anti coagulation and that's when we worry about bleeding. With prophylaxis heparin, we don't see bleeding and if despite full anti coagulation, if you choose to do so they have another throng biotic event. I think very strongly that that's probably a reason to take out the colon because that next third from biotic event might be a fatal one. Next slide. So remember that if you're looking at the mayo endoscopic score, it's not specific enough on the left, you see someone with mild disease, moderate disease, you see some erosions and severe disease. All that means is you could have a couple of ulcers, even rather superficial ulcers. And that might qualify for a level three next. But you'll see on the next slide that there's a lot of different level threes for instance, are these just mayo three. So on the left upper hand side, you see very broad ulcers pliability. You see no normal mucosa on the upper right. You look on the left, you now see big what we call bear claw ulcers and on the right you see, most of the mucosa is big, gaping holes. So these are not the mayo threes that we talk about when we look at controlled trials and there's one study from the early nineties that goes through these Kind of endoscopic appearances. And if you're looking at something in the bottom slide, the likelihood of collecting me, there is 90%. Let me make the point that when you're assessing and treating for severe colitis, you never need to do more than a sigmoidoscopy, you'll get all of this information the diseases most distal you only run the risk with the full colonoscopy. You could do this exam without sedation. To men it's going to 15 centimeters will be adequate. Next slide often they need no prep either. And the expression I came up with is you gotta have some mucosa to work with on the left. You see you have adam Enis mounds despite some big ulcers on the right. You see there's mucosa there with intervening ulcers. If you have that kind of mucosa there's some chance you'll get the patient better. Next slide on the other hand, if you look at this slide on the left you see on the bottom at about six o'clock or seven o'clock. New Coastal Island. The rest is all sub mucosa. That patient will not get better with seven days of therapy. Also, if you look on the right there's barely any intact mucosa there. So remember mayo three that you read it In clinical trials is probably a Mayo three. Like you saw the first slide not these subsequent ones keep that in mind. We don't need to do repeated sigmoidoscopy ease. You'll follow your clinical signs and symptoms and labs but if you're starting off with this you have to understand the likelihood of success is far lower. Next slide please. So steroids to sum this up if you needed steroids and this is prior to anti TNF therapy. But going up to 2006. So this is not looking at studies in true love which criteria in the 19 fifties and sixties. A quarter of patients who came in requiring I. V. Steroids needed collecting me on that admission and there were deaths and we can continue to see death in patients with severe colitis. Again you don't need more than 60 mg a day of cyber metro ivy or 300 mg of hydrocortisone next. And when you put a patient on steroids are obviously gonna send them home on something anyway so I usually make the argument if someone is sick enough to come into the hospital acute severe you see they've almost always had steroids already oral and just putting them on I. V. Steroids is not going to get them where you want them to be. And besides if a patient has been sick enough to be admitted there's something you're going to put them on as you taper steroids. So my approach is I put them on an anti TNF if they haven't already been on that and we'll get to that in a moment. The most important point I'll make is don't delay. Don't delay moving from your initial therapy. To quote salvage therapy. If you did use just steroids don't wait more than say three days and if you're on salvage therapy again 3 to 5 days we don't have 7 to 10 to 14 days to wait for this patient to get better. These are two criterias. Two very simple scores and subsequently there have been many many scores. This is simple. You have an 85% failure rate if by day three you're still having more than eight albums a day or a high crp. And by day seven if you have any blood you're probably going to fail. And again we shouldn't be waiting seven days just steroids. And again if you have severe endoscopic ulceration the likelihood of getting better is even lower. Next slide please. So we'll talk about the so called salvage therapy inflicts a mob and I'm fascinated to know what the axis is next slide and cyclosporin. Um This is a paper, a landmark paper and of course john fred the second to last author was instrumental in making this study happen. It was a very difficult study. Uh jean fred had explained to me because it's hard to take a patient who is facing possible surgery within the next week and say I want to put you in a controlled trial and they would probably say this doctor just do what you think is best here and this is in France. Uh They were told you're going to get one or the other. Both are proven effective and we'll see which one does better. And this trial has become known by its abbreviation, assistive trial patients failing I. V. Steroids they already failed. I. V Stewart in the hospital were allocated to the cyclosporin or inflicts on that next slide. And you'll see that at day seven collecting the avoidance rate and day 30 and day 90 the results were not similar. They were virtually identical. So it If you don't have inflicted map, you'll do just as well with cyclosporin. Although long term you'll have to transition because cyclosporin beyond say 3-6 months has toxicity. That is not tolerable typically in terms of renal function. But if you have inflicts a mob available and are not comfortable with cyclosporin which has been around for about 40 years, then you could use either one knowing you're using equally effective therapy. Next slide. And that's not just the day seven that's looking at at day 98. Very objective criteria with outright new coastal healing half the patients and again remember half the patients are not getting to that point. Next slide. And if you look at long term looking out the excuse me, during the 98 days, during every time point, the collect um, e rate is virtually identical. And if you look out to 98 days, the collectively rate is already about 20% in these patients who are treated with our quote salvage therapy is the term that we've uh started to use for years now. Next slide and long term. So this is again, as my beloved mentor used to say about crones disease and also colitis. These are diseases of a lifetime and anyone who has had a very acute presentation. Their phenotype of the disease is more severe and we think about what can we do long term to prevent a recurrence. So here you see that patients who are put on cyclists, warren versus inflicts a map patients with cyclosporin. This trial came off at six months and then they would put on something else. Mostly inflicts a map patients. For the most part, we don't treat long term with cyclosporin. And again, the good news here is if you have the access to the inflicts a map you do just as well. And even though it's quote a newer therapy compared to cyclosporin for severe ulcerative colitis, we have no res to think that it is not at least as effective. Next slide. And that is in patients who are naive to inflict some app. That's important to point out these patients in this study had not previously received inflicts a mob. Now an important point to make is salvage therapy. And I'm the gastroenterologist here. Gastroenterologists don't operate here. Surgeons don't treat with inflicts a mob or cycle is born in the hospital were sort of highly subdivided, but we are the ones who treat with medicine and I find that my goal is not to avoid surgery. My goal is to have a safe well patient. So looking at what we call salvage therapy, This is a nationwide study collection of information retrospective. So has all those qualifying statements from spain and they look three factors lead To increase mortality here we're not talking about collecting me, we're talking about mortality and it was aged over the age of 50. Very significant mortality collectively rate. In terms of specifically mortality. You see a higher mortality if you've had a collective me. And again, that is consistent with not that surgery is the problem, but that the patients probably waited too long to have surgery. Um And in terms of where they have their surgery and this is probably consistent with what we have in the United States. Spain is certainly not on any different level lower than else in terms of sophistication and access to these medicines. If you were in a secondary hospital, in other words, not at one of the academic centers that sees hundreds of cases like this, the mortality was 3.5% a tertiary hospital 0%. And my and they don't go into all the specifics of the mortality. But my strong guess is that in those hospitals they were probably waiting too long. I don't think there's any reason to think it was a surgical complication. They probably didn't treat aggressively and make the decision to go to surgery in time next slide. So do we do better by giving more than five mg per kilogram. And even the United States where often the infliction of dose and the cost is not the rate limiting factor. We have not found that 10 mg per kilogram is better than five mg per kilogram. And when we look at a multi varied analysis, it doesn't really show up that 10 is better. Now. The problem with that analysis is it's not control, it's not randomized. And if you think about it, we generally have not given the 10 mg per kilogram unless it was a very sick patient. So it's probably that the secret patients are getting 10 mg per kilogram are not doing better because they probably started out sicker having said that, and I'm john fred might at this point, still disagree, and I'm very interested to hear how he's approaching this. We do know now that patients who have such hot colitis, they will utilize that inflicts the map and their levels might go to zero within days. It pours out in the stool. So we like to think that we could maybe have better circulating levels by starting off with 10 mg per kilogram. My personal approach is if a patient's been sick enough to be hospitalized, I want to give them every best chance because I'm not gonna wait weeks or months, and I do give them 10 mg per kilogram next slide. So how about if they fail one therapy and salvage therapy, let's say inflicts a map or psych was born. They're not getting better. And again, I would want to see Significant dramatic response by the very latest 5-7 days, sees something convincing. Can you go to the other one? And I will say in a patient, I'll sum up the data who is quite ill and elderly and low albumin. I would be very reluctant because this has a not a great collectively salvage rate and has definite mortality. So if it is a patient, on the other hand has never been sick, who's a young patient whose album and is not terrible, I will consider it in discussion with the patient, but I certainly don't suggest it is a standard of care that every patient should have to salvage therapies. And again, it's whatever you're comfortable with because the collector me free rate is not great at the end of a number of months after having to do this, you basically identified a very sick patients. Next slide. And here you can see that there are serious infection rates. And this is from paper I believe John Fred had part writing as with just about every paper you'll see and that there's a very important, serious infection risk here. That's at least 10-20%. And remember these patients are on steroids. So treat usually, if not always. Uh and treating them at this point with antibiotics is certainly no guarantee of success. Next slide. Now, how about this approach if you're not comfortable using psychos foreign long term. So David Rubin was part of the study. This was, I believe a number of groups from europe and perhaps Hungary who put together a group of patients not controlled, 92% of them. Almost all of these patients had already failed T. N. A. Anti TNF inflicts a map typically and that's why they didn't get it in the hospital. So patients got as a planned approach. Seven days of ivy cycles boring and then with the hopes of getting them off early by three months they were off and they started the patient on vito early and gave them often. They had to dose escalate to every four weeks. And this obviously could be a cost prohibitive approach. But these patients who able to get a more cycles born by three months, they did not have the same kind of complications and serious infections by having veto on top of cyclosporin again, cyclosporin on top of inflicts a map far more likely to get complications. So this is definitely something to consider is bringing back cyclosporin because a lot of these patients have already failed. Inflicts a map. Next slide please. Now is getting a lot of attention and I don't know Alex do you have available? Not yet. No inflicts the mob in the hospital cyclosporin sometimes. Yes. Okay so cyclosporin, I could do a whole talk on that but people are not comfortable in in in the next 60 seconds. And I wrote a paper 25 years ago called cyclosporin a user's guide which was very practical. It has to be a continuous infusion. Generally two mg per kilogram over 24 hours. We shoot for levels about 2 to 400 on the cyclosporin if you can't get a cyclosporin level back quickly. A surrogate marker that I found you can use if the blood pressure is okay and the creatinine is not rising you probably are doing okay with that dose. If the blood pressure is rising the creatinine is rising you probably are in too high A. Level If you are limited as most people in the United States were not using cyclosporin because they cannot follow the levels to facilities for treating refractory you see. And frankly if we could get doses of this medication which is easy to get to than I. V. C. Steroids are excuse me, ivy infliction or ivy cycles born. This is a pill and there's now increasing data all open label. But Peter Higgins did a study. He put patients did not randomize them 10 mg. T. I. D. And our usual dose for induction is 10 B. I. D. The patients who he put on 10 mg T. I. D. Three times a day for just three days and then went to 10 mg. B. I. D. He had a very impressive collecting me avoidance rate. There are other this isn't patients who had already failed steroids and a biologic. There's a small group in japan. All four patients they had failed to biologics and they gave them to facility in that dose. So if I'm going to use it in the hospital we've there have been several patients at Mount Sinai. And interestingly enough even the Great Mount Sinai they don't keep it in the hospital. We have patients bring their own to facilities or we get samples frankly. Um And these patients do well I'm not enamored I don't like the idea of to facilities on top of cyclosporin or inflict. So mad because I think they're the toxicity is going to be significant. But these were patients who had failed inflicts a map. Next slide. Okay so this is basically showing the data in terms of the collector me rate at 90 days. If you're looking at the left 15% and 180 days 20%. So this is probably significantly better even than in patients who were treated um straightforward but again this is even in patients who had already failed inflicts a matter. And if you look on the right the patients on 10 T. I. D. Regimen and again that was just three days did better. Next slide please. So I'm gonna finish by what I call The 10 top pearls and pitfalls and managing acute severe ulcer of clients. And this is the term that we used to be all over the map when I wanted to do a pub med search I look up severe colitis and now there are tens of thousands of articles because all the biologics approved for moderate to severe ulcerative clients. And those patients in the studies are always outpatients. So fortunately we now have a term that most of us are being are using. So it's easy to search on in the literature acute severe ulcer of colitis generally refers to the hospitalized patient when looking in the literature, avoiding narcotics and anti colon urges. The anti spasmodic meds. Very important because this patient is sick enough to be in the hospital. The risk of mega colon is significant. Secondly the abdominal exam obviously is an important feature and giving them narcotics you're going to mask that the differential diagnosis. Everybody should obviously be checked for C. Difficile. And frankly if the patient has been in the hospital for some time and you can't get a stool back for C. Difficile I would say because I've even done this at Mount Sinai when we used to have to wait two or three days to get a C. Diff result back. That was before we had the D. N. A. Pcr panels. I would treat the patient empirically with Vanco Missin. The infectious disease. Doctors would have killed me because they're worried about vancomycin resistant enterococcus side. Now we have these D. N. A. P. C. R. S. That are far more accurate we get them back within the 1st 24 hours and if they are C. Diff positive they have a much worse survival in terms of color. In every study those patients should get vancomycin as opposed to um Metro night is all this clear benefit to vancomycin. And the doctors in which you might not have. Likewise better than Metro night is all C. C. M. V. On a biopsy sometime is there? Because the colon is so sick. And if you have a very sick colon you might be inclined to treat for seven days or 10 days. Just with treatment for the C. M. V. As your goal. That's probably a mistake. If the patient is very sick and not getting better. Don't wait for C. M. V. To improve start D. V. T. Prophylaxis on admission and what we would call the sicker patient. The older patient bad album. And I've never seen a patient who has an album of two or less ever still have their colon in three months. And those are the patients who are the sicker ones. They are more likely to run into trouble. Lower not higher threshold for surgery. The surgeon will often tell you the patient's too sick for surgery. That's often the patient who needs surgery the most. If you're going to use a therapy whether it's cyclosporin or inflicts a mob or to first consider it early. Consider transferring to a specialty hospital. And again think about everything earlier in the course have the patient meet the surgeon early. This is obviously a life changing event and the patients shouldn't be told, oh let's have you meet the surgeon because today you're having your operation. So we like to have the patient no matter what our expectations are Meet the surgeon early. If the patient has fulminate colitis, they're toxic. Think about collecting me sooner and that the case is even more urgent and what I call a reality check many times we've taken care of these patients for years. They feel like family and we don't want to do the collecting me. We get a second opinion for someone who says, you know what this patient is clearly ready. I don't know what you're waiting for. Sometimes you just need another pair of eyes next. And my most important point is if you have severe colitis and in your judgment, you've done everything you're comfortable doing. Whether it's just steroids or inflicts a map And you think it's time for surgery. Do not delay because only bad things can happen hemorrhage. And I've seen unfortunately all of these hemorrhage, bad sectors, robotic events that could be fatal perforation, obviously. And even death, this is still a potentially fatal disease. So with that, I conclude. And if you'd like to ask questions that I could do it now or at 10:00, whatever works for you. You have something in that I don't know if you wanna in the chat. Yes, thank you so much. But maybe Alex can because maybe Alex has a lot of questions from his uh website because Alex maybe. Yes. Uh so yeah, we have this question in the chat. And uh I have a couple questions uh which we usually see like you mentioned that uh 60 mg of methylprednisolone is initial treatment or some steroid equivalent to 300 mg of the hydrocortisone. Why not hire? Because in Ukraine everyone almost everyone is doing higher those because there there's at least one randomized control trial where they went far higher so that there's no question literally 1000 mg a day of solu Metro you're not. Is that what's being used? No better? It's no better than the lower doses because to us that's still a massive dose. It's the equivalent of 16 milligrams of predniSONE intravenously. And so even when we're going from 300 mg of hydrocortisone or 100 or 60 mg of Metro when they go to oral there obviously getting a significant lower dose and there's no benefit. I would say that they're probably being over treated and significantly increasing the risk. Okay. And and the second question I have you mentioned almost empirical treatment of the city of what about C. M. V. Do you have to take a biopsy? No. No I would definitely say, first of all in c that's an important point to make is the patients who get sickest with the C. Diff and in whom the c diff is the most difficult to get rid of our patients on steroids and flicks a map does not appear to increase the risk that is a patient who by definition if they're on inflicts a map or psycho spawn. It means the I. V. Steroids haven't worked. I look to try and taper the steroids if the patient can clear their c diff and there is a question in the chat from dr Bahar. Um uh do you always choose a step up therapy? They mean first steroids and then biologics or you can you can begin from biologics. So I think john fred and I may be debated this at some point. I would say you don't have too much room for the patient to get better. And if you put a patient on I. V. Steroids if they're that sick you're gonna have them on some biologic anyway you're not going to put them on predniSONE when they go home and taper it and leave them on a. Five A. S. A. Drug. You're gonna have them on some biologic. All of the biologics are safer than six. More capital appear in the south. I prin if I'm gonna have the patient on a biologic. I started as soon as they come to the hospital. I think the era of just treating with steroids is what dr true love and dr Wittes did in the 19 fifties. And since we have these studies and know that the collectively rate is high. If you're coming in for steroids and you need another option anyway. I put them on one of these therapies right away. Yeah I just want to add that on our previous webinar we explicitly discussed this topic and uh um I think that's not a question about the um acute severe colitis itself but regarding the contraception in IBD high risk of thrombosis and malnutrition and things related to that. How that what is the usual approach for the patients who is using contraception in the IBD? Okay so we treat the pregnant patient. I don't know if there's a separate lecture on pregnancy all the same. The most important feature to maintain a healthy fetus and a healthy delivery is keeping the colitis under control. All the medications we use. We continue and we emphatically say don't stop. Obviously methotrexate is out. We have very limited data on to facility nib in a pregnant woman and of course to facilitate increases hyper collectibility. I would say that if you're now patient you're putting the patient on to visit in it because that's your best option. You try not to do it in a patient is hyper collectible. But if you have no other options and the patients all contraceptives, I would try and get the patient on an alternative method of contraception. Thank you. Thank you so much. A shell. This was amazing. As always we we can we can see that this is one of our preferred topical. He's I think he's really passionate about that. Thank you so much. ASHA I know you are very busy today and whatever you need if you need me to come back for questions, I'm happy to okay thank you so much.