TRANSCRIPT:
Welcome everyone to IBD Drive Time. I'm Raymond Cross from Mercy Medical Center in Baltimore, and I'm delighted to have my good friend and colleague, Anita Afzali from University of Cincinnati here to talk about the new ACG guidelines in Crohn's. Anita, welcome to IBD Drive Time.
Dr Afzali:
Thanks, Ray. I'm very happy to be here.
Dr Cross:
So Anita, what I tried to do is—these guidelines are very big and it's hard to sort of go over everything—but I tried to come up with some questions or concepts that were relatively new or maybe that were something that would change practice. And obviously at the end I'm going to ask you anything that we didn't include that you want to talk about. But the first thing is, one of the things is determining disease severity. So someone's prognosis for a severe disease course. So what did the guidelines tell us about features that were associated with a high risk for more aggressive Crohn's disease?
Dr Afzali:
Yeah, so in the ACG guidelines, we tried to introduce several advancements aimed at improving patient outcomes. And this is through personalized approaches, enhanced diagnostics, and even the expanded treatment options within the guidelines. And certainly one component was providing some guidance on helping all of us identify and better understand who our patients are that we deem as higher risk for disease progression and disease related complications. The guidelines lays out several red flags, if you will, for aggressive disease, and that includes age being under the age of 30, but having deep mucosal ulcerations on endoscopy, extensive small bowel involvement, perianal or complications, early steroid use, prior surgery, prior intestinal surgery, smoking. So these are some features that we've identified at placing our patients at are higher risk for disease progression as well as complications related to that. And certainly this helps us identify which of our patients would benefit from a proactive approach to therapy.
Dr Cross:
Anita and those patients that certainly have, it's I think inarguable that they would've more than one of those. So certainly you start to see multiple of those, there's good evidence that that's consistent with a more aggressive course. So those patients have to fail conventional therapy or can they go right to an advanced therapy?
Dr Afzali:
Yeah, thanks for asking that, and no. Right, so that's definitely a major shift that we really wanted to emphasize in the guidelines. High risk patients do not need to fail the conventional therapies like the mesalamine or even extended steroid courses of therapy before initiating early appropriate advanced therapy. And so the ACG guidelines support early initiation of whether it's biologics or small molecules in patients who are likely to experience disease progression, and delaying effective treatment either following the step-up approach or step-up therapy in these high risk individuals, the factors that we identified earlier can actually worsen the outcomes for our patients, and so this will increase the chances of our patients suffering from a fistula or a stricture or needing surgery or other complications. I want to be very clear that this is not us saying that we're promoting aggressive therapy. This is about early appropriate therapy for an aggressive disease or an aggressive disease phenotype. And one of the core reasons this language is so important, and we were very intentional about it within the guidelines, is hopefully for us as clinicians to understand it and also for the insurance companies and the payers to also understand and help recognize the clinical necessity and certainly also the cost effectiveness of taking the approach of early appropriate therapy, finding the right treatment for the right patient at the right time, and recognizing that any delay in that could actually harm our patients and be quite costly.
Dr Cross:
Yeah, I think that's beautifully said. And I think for the listeners, just to reiterate that if your patient has risk factors for a moderate-severe disease course and or moderate-severe disease activity as defined by symptoms and inflammatory burden, they are an immediate candidate for advanced therapy. And I would argue that we should potentially be trying to look at who doesn't have moderate to severe Crohn's, because those are the patients that maybe you can do dietary therapy, tapering course of budesonide. Maybe that's the sulfasalazine, colonic Crohn's patient that you could utilize instead of thinking about who we should be giving it. Most people with Crohn's should be getting an advanced therapy, not the minority, which is unfortunately what still happens in our country.
Dr Afzali:
Absolutely. I definitely agree.
Dr Cross:
So speaking about what not to do, does the guidelines recommend against us doing any specific therapies or any specific testing?
Dr Afzali:
Yes. So the guidelines actually say there's a few do nots, right? And one of them, which unfortunately we're still seeing a common behavior, if you will, of is the prescription of the mesalamine or the 5-ASAs for patients with Crohn's disease. And we have definitely demonstrated, and we've again included this in the guidelines, that this is not an effective treatment for Crohn's disease and should not be used for either induction or maintenance of therapy.
The other component is that we have mentioned and demonstrated and included in the guidelines that steroids should not be used as maintenance therapy. It should be strictly for use for symptom control. And as I often state to my fellows and my colleagues, anytime you're writing a prescription for steroids, it should very much be for yourself and for the discussion with the patient, which is, this is a bridge to what? In other words, what's my next step? What's our next step that we're going to take? Will we be optimizing your current maintenance regimen? Do we need to change it, switch it, stop it, what do we need to do? And so it's only a bridge towards something else.
We also include in the guidelines some other do-nots, and that's what the diagnostic testing and specifically the serologic antibody panel, as the Prometheus testing as an example, we don't really recommend that. We don't feel that it really is necessary as part of that diagnostic or therapeutic decision making capacity or influencing our ability for that. Now, I don't want this to be confused with the genetic markers, whether it's the HLA DQA-1 or the NA2 or the TPMT. These are different because these are markers that may help us predict in individual patients as far as what certain therapies are not appropriate. Perhaps we could tailor our treatments more safely and effectively for these patients based off of their genetic markers and then also potentially minimizing adverse events or harm to our patients.
Dr Cross:
Anita, I assume that that doesn't, you're not discouraging people from using a tool like CDAF that does include some serologies that are more prognostic. And again, I think that it maybe is more helpful for identifying that patient who's at lower risk for complicated disease. I presume it's still okay to do it for that reason.
Dr Afzali:
Yeah, yeah, that's a good clarification. And yes, I agree it is more for the diagnosis of where I don't think that we felt there was enough evidence to incorporate as part of our guidelines to say that the serologic antibody panel for the actual diagnosis should be utilized as a way to make the final diagnosis of Crohn's.
Dr Cross:
One more question before we talk about some announcements. Is there a preferred cross-sectional imaging study recommended in the guidelines?
Dr Afzali:
Yeah, we recommend the MRI enterography or even intestinal ultrasound. Actually, we've incorporated this into the guidelines as the preferred modalities. And we've recognized, and definitely as we know, these are noninvasive, it's radiation-free and it's an excellent way for tracking disease progression as well as complications. Now certainly there's areas where maybe there's organizations or institutions that may not have access to some of this, and CT enterography can be an option when MRE or MRI enterography is not available. And then again, we're shifting a little bit more with understanding the utility of the intestinal ultrasound, which could also continue to grow as far as a good way of a noninvasive way of monitoring disease.
Dr Cross:
So before I go to some more questions, just I want to remind our listeners that we are sponsored by the AIBD network. You can find us on both Spotify and Apple Podcasts. And our next regional AIBD is going to be in Detroit August 23rd to August 24th, and I will be there chairing that meeting. That's very good memories for me when the Steelers won the first Super Bowl with me in attendance. So it'll be very good memories to go back. We're not going to talk about the Pittsburgh Steelers though anymore.
So Anita, the guidelines typically are going to mention we have so many advanced therapies, they're wonderful, they work, but as far as unless you have head-to-head, it's hard on a guideline to really position, but there were some specific recommendations in patients that had been exposed to anti-TNF previously. So which medications should we be using preferentially or maybe which shouldn't we be using in that situation?
Dr Afzali:
So again, as you've described, we definitely wanting to take the approach on the guidelines of recognizing that positioning and totality is so patient-specific that it would be hard to delineate in that accord. But recognizing that if a patient has had a primary nonresponse in anti-TNF therapy, the recommendation is, and that's what we incorporate into the guidelines, of switching classes of therapy. And this would be preferably with either ustekinumab and IL-12/23 inhibitor or with our p19s as an example, and through the guidelines, we are actually advising against cycling through the anti-TNFs in these cases, unless of course it was a clear immunogenic failure.
Dr Cross:
And how about JAK inhibitors? So that's still appropriate in that setting as well?
Dr Afzali:
Absolutely. And as you know, we have the limitation with the boxed warning and then also with the restrictions. So this would be appropriate in that consideration because these are an individuals who have had a failure to respond or no response with an anti-TNF. So a JAK inhibitor as a small molecule can and should be considered.
Dr Cross:
So another thing that I noticed is it's pretty consistent amongst all of the societies that if you're using an anti-TNF, combination therapy is recommended. And I think that's because our best trials have shown that combination therapy is better. And excuse me, I think also that there's still a group of providers that are not advocates of proactive drug monitoring with anti-TNFs, but we know in the community about 15% of the community is actually using combination therapy. So are you using combination therapy? If you are, is it in a subset of patients or are you using proactive drug monitoring with anti-TNFs as an alternative? How are you practicing? Because I'm a proactive person, but I do have some groups that I do use combination therapy.
Dr Afzali:
Yeah. So I'll start with the first part of yes, I'm also utilizing combo therapy and by combination therapy it's a biologic with an immunomodulator, whether it's methotrexate or a thiopurine, we're not talking about combination of anything else in that regards. And for pretty much the majority of my patients when I'm starting an anti-TNF, especially that first year, I'm doing combo therapy. And these are among patients specifically if they're bio-naive, for example, a high inflammatory burden younger age, or those who I know are at higher risk of developing antibodies. For example, if I check the HLA DQA 1*5 as an example, and there are select times when I may not do combination therapy, and that's especially in my older patients for example, or those at a risk for malignancy, at a higher risk for malignancy, maybe I would avoid in that particular.
As far as the proactive-reactive TDM, I am not a proactive TDM type of person. I don't think it would necessarily change what I would already initially do in regards to starting that combo therapy. But there are certain phenotypes—meaning fistulas, aggressive perianal disease, high inflammatory burden—where I would do combo therapy and still I would want to do some proactive monitoring to be able to determine if I need to optimize dosing in advance as well in addition to that concomitant agent.
Dr Cross:
So for the listeners, I want to make sure that they understand that what I'm saying is maybe not what the guidelines are saying so it's clear. I think generally you should be following the guidelines as closely as possible. But I certainly for my perianal Crohn's patients, I'm giving them combination therapy and I'm trying to treat them both maximally because that's such a difficult group to treat. And then the patients who've had prior response, but lost response due to immunogenicity, if I'm going to go to a second anti-TNF, I almost always am going to use at least concurrent like low-dose methotrexate, but I tend to get away with monotherapy because I'm aggressive with checking levels. But just for the listeners, the best evidence is still for combination therapy, so you should be more like Anita and less like Ray.
Dr Afzali:
And that’ always the case, isn't it, Ray?
Dr Cross:
Yes. But maybe Ray is an alternative to Anita.
Dr Afzali:
Debatable.
Dr Cross:
Anything else you want to highlight from the guidelines that maybe we didn't talk about? There's a lot in there.
Dr Afzali:
Yeah, there is a lot in there. And first and foremost, I didn't start with this, but I definitely want to recognize all the coauthors of the guidelines, of the reviewers and the entire publication staff and team that help bring this to fruition. I think the guidelines, as you know and saw, there is a lot to unpack from it. As you saw, there's 35 different recommendations and nearly 60 key statements or key concepts. And so again, a lot that I encourage our listeners to be able to download for free as a PDF from our ACG website, as well as the visual nice summary slide that was created actually by Dr. Erica Duh and Dr. Tina Ha, which is a nice clean single-page infographic of a summary that succinctly captures all of these recommendations, helps with risk stratification, therapeutic hierarchy, being able to incorporate the postoperative management, even preferred therapies and so much more.
So I encourage all the listeners to get on the website and be able to download both the guidelines in totality as well as the visual infographic. There are again, some important principles I think it's important for us to highlight and really recognizing that in these guidelines. First and foremost, we were very intentional with reinforcing the idea of treat to target and really emphasizing the importance of type control, whether that's via monitoring the biomarkers, fecal calprotectin, CRP, as well as imaging to help guide our decisions. So really bringing and reinforcing the treat to target strategy for us as a way to manage and care for our patients.
The other component within the guidelines was the importance, as you and I know, Ray, of shared decision making and really again, aligning the decisions and the management approach with it being patient-centric, aligned with the patient goals of therapies, incorporating medical comorbidities as well as patient preferences when it comes to the therapeutic options that are available for our patients.
We tried to provide a really great summary on the postoperative recurrence prevention as well, and really outlining specific strategies once we were able to stratify between the low risk and the high risk postoperative patient, meaning for the risk of disease progression after they've had that surgery. And really what approaches could be taken to help with the management of the disease and hopefully lessen that risk for disease recurrence. So in short, I think our guidelines were very intentional with bringing about a individualized proactive care approach and recognizing that that one size fits all algorithmic strategy just doesn't work and we need to be able to take that approach for each individual patient of ours. So I really hope that we were able to, through the guidelines, provide some level of help and I hope our listeners will find it helpful as well.
Dr Cross:
Can we spend a minute or two just talking a little bit about treat to target? And I know you so well and we've been in presentations together and other things where we've had these discussions, but certainly the ACG guidelines committee is not recommending that you cycle through 3 therapies to heal every single aphthous ulcer. So that's not what treat to target is.
But I'll give you a good example. I have a delightful 19-year-old I saw this morning who is on a biologic therapy and he's had clinical improvement, 90% reduction in CRP. He's had near complete healing of the ulcerations in the colon, but still has several large ulcers in his terminal ileum. And we had a shared decision making discussion and I said, I don't know what the right thing to do is in a patient like you. We don't know how far we need to treat you. We know you're better. You certainly could continue your therapy with close monitoring, or maybe we could switch you to p19 inhibitor instead of your p40 and it's unlikely you're going to get worse and you may get better. And with a good discussion with his father and myself and he decided I want to be as close to perfect as possible.
Now, I think that's sort of an easy change because I think the odds of getting worse is very, very low. But it is hard sometimes because our therapies, particularly for ileal disease, don't work; 80% of the time they're not as effective. So these are tough decisions that we have to make.
Dr Afzali:
Indeed, they're tough decisions, but I think your approach is the approach that we're all encouraging and we should all practice, right? Shared decision making, recognizing how bad was the before picture and where are we at today and what objective components as well as subjective in a sense of components have improved or have not improved to recognize and determine the need for optimization switch change or not. And as the saying goes right, don't let perfect be the enemy.
Dr Cross:
The perfect. Don't let perfect be the enemy. Yes
Dr Afzali:
Yes. So let's not do that and let's just be able to look at each individual patient and determine through shared decision making on whether it's appropriate or not.
Dr Cross:
Alright, Anita, this is a fun question. So did you always want to be a doctor? And if so, what got you interested in Crohn's and colitis? And then if not, what did you want to be before you changed your mind and wanted to go to med school?
Dr Afzali:
That is a fun and interesting question, so, well, no, I actually never thought I wanted to be a doctor. I initially thought I wanted to be a journalist and a TV broadcaster, maybe even a podcast person to work alongside you, Ray. But no, I did not think I wanted to go into medicine. I think ultimately my journey steered me into medicine just recognizing that this was a level of service and impact that I wanted to be a part of and commit towards.
And what got me interested actually in bringing me into the IBD world is recognizing the complexity of care that it requires. And truthfully, the profound opportunity to be able to walk and work alongside the patients we serve, to be able to advocate for care, for innovation, to be a clinical trialist and be involved in drug design and discovery and hopefully one day a cure. And to be able to bring both science, medicine, compassion all together. And the IBD community is one of the best communities to be a part of that I'm privileged to be a part of and to work, of course, alongside friends like yourself.
Dr Cross:
You're an outstanding doctor, but I could definitely see you as a medical broadcaster. I do not think that's farfetched.
Dr Afzali:
I know, I know.
Dr Cross:
Definitely do that.
Dr Afzali:
Well, if it wasn't a journalist, it was going to be a UFC fighter, so that was the other part. But maybe that part is less likely, huh?
Dr Cross:
Yeah, I think at a certain point you're probably not going to be a UFC fighter, so. Alright, Anita, this has been wonderful. Thanks for doing this. We'll definitely have you back on and I hope to talk to you soon.
Dr Afzali:
Thanks so much for having me, Ray.
