Exploring the Evolving Treatment Landscape for Inflammatory Bowel Disease

David Hudesman, MD: Thank you for joining this MEDcast series titled“Exploring the Evolving Treatment Landscape for Inflammatory Bowel Disease.” I’m Dr David Hudesman, a codirector at the Inflammatory Bowel Disease Center at NYU Langone Health in New York [New York].

Jordan Axelrad, MD, MPH: I’m Dr Jordan Axelrad, the director of clinical and translation research at the Inflammatory Bowel Disease Center at NYU Langone.

David Hudesman, MD: In this program we’ll delve into the long-term management of inflammatory bowel disease and examine the latest treatment options and strategies that can enhance patient outcomes. To discuss more of this, we’re joined by Dr Douglas Wolf, a gastroenterology specialist in Atlanta, Georgia. Thank you so much for joining us. Let’s jump right in.

Dr Wolf, tell us some of the major challenges you have in managing patients with inflammatory bowel disease?

Douglas Wolf, MD: The biggest challenge is the fact that inflammatory bowel disease—both Crohn disease and ulcerative colitis—is a heterogeneous group of disease. There are many forms. For Crohn disease, you can ileo-rectal Crohn, colonic Crohn, fistulizing Crohn, or extra-intestinal manifestations. There are similar challenges with UC [ulcerative colitis]. There are many forms, and we don’t have solid tests to identify which treatment is going to work for an individual patient.

David Hudesman, MD: That’s a great point. We all have patients who come in with a friend or a family member who’s had this type of disease or been on this treatment, regardless of whether they’ve done well. We have to explain to them that their disease is personalized. We need to discuss that with them up front before we go into treatments.

Jordan Axelrad, MD, MPH: Dr Wolf, tell us about how the treatment landscape has changed, especially in recent years, and how that’s influenced your way of approaching patient management and drug selection.

Douglas Wolf, MD: We’re trying to individualize and personalize care for every patient. What’s right for 1 isn’t necessarily right for another. In the past, it was 1 shoe fits all, and patients got a form of mesalamine to start, then prednisone and maybe an immunomodulator. But in the last 10 or 20 years, we’ve had an increasing variety of biologics, which are individually very beneficial. But we don’t know which 1 is going to work for whom. We have many more choices, and we’re learning how to use these options even better. I hope that answers the question.

David Hudesman, MD: That’s a great point. The 1 thing I always try to pass along to patients is that whatever the treatment is, what we’ve seen—more with the Crohn data than the ulcerative colitis data, but I believe it’s true for both—is that we want to treat them early. We say, “You’re a patient who’s not doing well now or set up for trouble down the road, so we want to initiate our biologic or small-molecule treatment early.” If we initiate it early, because we don’t have good predictors, which therapy we choose matters a lot less. Unfortunately, we see a lot of patients 2, 5, or 10 years down the road, before they get appropriate treatment.

Jordan, tell us a little about your approach to treatment.Take out the therapy first. What are your goals of therapy? Whatare you discussing with patients?

Jordan Axelrad, MD, MPH: When I’m seeing a patient in the office, the first thing I do is assess their background disease. You want to know their disease activity and disease prognosis. We use many tools to help us evaluate that with some scoring mechanisms. Obviously, we want to know what their endoscopic activity looks like. That’s included in many of our scores, and it differs. For patients who fit more of severe criteria in ulcerative colitis, I may be thinking about different drugs, anti–TNF [tumor necrosis factor], infliximab [Remicade] in particular. For patients who fit more moderate criteria, I may be thinking of different drugs, anti-integrins like vedolizumab [Entyvio] or even ozanimod [Zeposia]. In Crohn disease, it’s the same thing. With very severe disease activity and prognosis, I’m thinking more about anti-TNF therapies like infliximab. For more moderate disease, I may be thinking about the IL-12/23 and IL-23 drugs, such as risankizumab [Skyrizi] or ustekinumab [Stelara]. Taking in all those considerations, the drug selection has changed.

David Hudesman, MD: Doug, what are you telling your patients about the goals of therapy? If you start them on a particular therapy, how are you monitoring them when you’re saying you’re happy or not happy with the response?

Douglas Wolf, MD: It’s very important to follow all these patients closely, so I see patients back in 4 to 8 weeks. And they have rapid access to reach me, so I can get them in earlier if need be. But we want to see that the initial course of therapy, which we call induction therapy, is working. If it’s not, then some of the time, there’s some other explanation that we need to understand and analyze. It could be that there’s a stool infection such as C diff [Clostridium difficile] that maybe wasn’t identified or appreciated early. But the bottom line is that we need to individualize these treatments.

With biologics, we sometimes need additional treatment. We sometimes need to use an immunomodulator if we hadn’t initially. Sometimes it’s dosing issues. With the advanced therapies, I’ve seen them work as fast as biologics. At other times, they can take more time. These treatments are agents like ozanimod and upadacitinib [Rinvoq]. They may or may not take a little more time. At least I can see the patient, talk with them, reassure them that we have to give it a little more time, and make sure there’s nothing else going on.

Jordan Axelrad, MD, MPH: Doug, you mentioned ozanimod and upadacitinib. Tell us a little about how you choose the right patient for those drugs. What are you thinking about and evaluating?

Douglas Wolf, MD: They’re both great choices. The advantage of ozanimod is that it’s FDA approved for both bio-naïve and bio-experienced patients. If you have a patient who failed on mesalamine and a steroid or something else, give ozanimod a try. It’s very effective. On the other hand, upadacitinib, another very effective treatment, is reserved for patients who have failed anti-TNF therapy in the past.

David Hudesman, MD: You mentioned that with ozanimod a lot of data show benefit in that bio-naïve population. When we’re trying to select therapy for a patient, is this the first-line therapy? Last year you presented an abstract at ACG [American College of Gastroenterology Annual Scientific Meeting] looking at a post hoc analysis of True North, the phase 3 trial for ozanimod looking at endoscopic severity. How does endoscopic severity affect you choosing therapy, specifically with ozanimod if that matters?

Douglas Wolf, MD: One great feature that’s well documented with ozanimod is that regardless of baseline disease activity, whether it’s moderate or severe, and baseline endoscopic activity, whether it’s moderate or severe, ozanimod’s efficacy is well demonstrated by significant reductions in calprotectin levels and other measures. It works well for bio-naïve and bio-experienced patients, those in the moderate realm and those in the severe disease activity realm. It covers a broad range of patients.

Jordan Axelrad, MD, MPH: What’s important about that is this new class of small molecules is oral. This is a new area. How we can take care of patients without injectables or infusions? This offers an opportunity to provide a mode of administration that we haven’t had in recent years, which is important.

David Hudesman, MD: That’s how I’m using it in my practice. If I have a patient on that moderate-to-severe ulcerative colitis spectrum—the more moderate end is bio-naïve—that’s where the strength of the ozanimod data is. If there’s failure of 1 biologic, there are some good data there as well. Once you get to multiple biologic failures—I don’t usually go to this as the next step—that’s where it fits in nicely. It has worked well, whether they have a Mayo Score of 2 or 3, meaning moderate inflammation on colonoscopy or ulceration. Then we have that discussion: efficacy, safety, is the patient traveling a lot? Do they have to come in for an infusion or injection? Having that oral option is important. Talk a little about safety of ozanimod and your thoughts about the safety profile or anything that concerns you.

Douglas Wolf, MD: There really isn’t. It’s a relatively safe agent in the context of the other agents we have to offer. There’s some initial testing done, as with other agents. It includes some cardiac monitoring done initially. Ozanimod doesn’t cause any cardiac issue. It’s a matter of being sure that everything lines up. Basically, it’s some blood work. The safety has ended up being very favorable. I’m very comfortable offering it to an array of patients with ulcerative colitis.

Jordan Axelrad, MD, MPH: It’s important to keep in mind with ozanimod that patients with cardiac conduction abnormalities are the ones you have to be careful of. Check their baseline ECG [electrocardiogram], and make sure they’re candidates for therapy. Although in inflammatory bowel disease, because many of our patients are younger, they don’t have as many cardiac comorbidities, so that’s not an issue. We don’t have as much data using this agent in women who become pregnant.

David Hudesman, MD: The only other thing I’ll add is that the lymphocyte count in half the patients will drop, but that’s expected. It plateaus after a couple of months on treatment and stays that way. That drop in lymphocyte count—we expect that with thiopurines—hasn’t been associated with any severe or serious infections. It’s something to be aware, but not something to be nervous about.

Douglas Wolf, MD: Exactly. I’ll add that we’ve published on that. Although some relative lymphopenia occurs, it’s not associated with any untoward events. There’s still a sufficient number of lymphocytes circulating despite the mechanism of action to protect us. We should feel comfortable with that.

David Hudesman, MD: For moderate to severe ulcerative colitis—the way I look at it, more on the moderate end—we have vedolizumab, ustekinumab is a good option, ozanimod. We talk about this because of good efficacy with a nice safety profile. Doug, what about upadacitinib? It’s 1 of the other new oral small molecules that the FDA recently approved for moderate to severe ulcerative colitis. Talk a little about that agent and how you’re incorporating it into your practice.

Douglas Wolf, MD: Upadacitinib is a JAK inhibitor. Because it’s in that class, a patient has to have failed an anti-TNF before utilizing it. But if the patient is ready for the next step after going through an anti-TNF, upadacitinib is an excellent option. Similar to Zeposia [ozanimod] in a way, it can be an excellent alternative to biologic therapy. Both options can be used even in patients who failed 1 or 2 biologics. I’ve seen them work. It’s a different mechanism. As with many other agents, when we try them as a second or third choice, they don’t work quite as well as if we had used them as a first choice. The data suggest that, but they still work. That’s where it's appropriate to reassure our patients that it may take a little longer to work. But getting back specifically to upadacitinib, it’s an excellent choice with activity. Its effectiveness is similar to what we’ve seen in biologics.

Jordan Axelrad, MD, MPH: We mentioned the adverse effect profile and some of the monitoring that has occurred before initiating ozanimod. Is there anything you’re doing with upadacitinib in particular or the JAK inhibitor class more generally?

Douglas Wolf, MD: No, and you may be able to address the specifics a little better. But there are class cautions. There are patients who have cardiac disease and cardiac morbidity. Those are individuals with whom we’d be more cautious about using upadacitinib. But the vast majority of patients with IBD [inflammatory bowel disease] don’t fit in that category, and so it’s an excellent option.

Jordan Axelrad, MD, MPH: I agree. It’s similar to the ozanimod risk profile. A lot of our patients don’t have a lot of cardiac comorbidities. Some of the big ones with upadacitinib are the risk of venous thromboembolism: PE [pulmonary embolism] and DVT [deep vein thrombosis] . Those have popped up in some of the post hoc analyses of use of tofacitinib [Xeljanz], which is another JAK inhibitor and an oral small molecule for moderate to severe ulcerative colitis. Also there are some infection risks—Zoster, the shingles—that we’re identifying as well. But our patients would be lower risk.

David Hudesman, MD: That data have come out, and many of us are well aware from a rheumatology study that these are older patients. When we look at this class in our patients with ulcerative colitis, young and old, we haven’t seen that. We still need longer-term follow-up. It’s something to be aware of and discuss, but it’s not a reason not to use a therapy. Jordan, what has your experience been? What type of patients are you using upadacitinib in?

Jordan Axelrad, MD, MPH: This is reserved for patients who are anti-TNF refractory. In general, these patients are going to be a much sicker patient, more severe on the moderate-to-severe spectrum. That’s who we’re using the drug in. These are infliximab, IV [intravenous], anti-TNF failures. The benefit of a drug like upadacitinib, as with most oral small molecules, is that it also tells you whether it’s going to work very quickly. If patients are going to respond to drug, they usually start to feel better early on in the treatment during the induction period, which is important. But I reserve this for sick patients who have failed other biologics.

David Hudesman, MD: I have 1 more comment on this. I agree completely. When I’m looking at the moderate-to-severe spectrum for ulcerative colitis, moderate is vedolizumab, ustekinumab, and ozanimod. Severe doesn’t mean hospitalization, but we’re talking infliximab and upadacitinib. I’ve seen very good results. There have been some nice post hoc analyses showing that within a couple of weeks, over 60% of patients don’t have any more rectal bleeding. When we’re talking about goals of care, we want the calprotectin to drop. We want the CRP to drop. But we have the patients. We want them to feel better quickly. Those agents work very quickly.

Jordan Axelrad, MD, MPH: One of the lingering questions we’re encountering and learning from is how we can sequence some of these drugs—vedolizumab, then ozanimod—in that patient. What do you think about that moderate who’s failed a biologic? Would you be thinking about a different agent there?

David Hudesman, MD: Yes, I think so. That’s a great question. I still look at severity when approaching positioning or sequencing on the severity. I like to go to what’s worked in the past because we don’t have…very good predictors of response for our therapies. If a patient has done well on vedolizumab for years and then lost response, and it’s unclear why that happened, ozanimod would be a good option. It has a similar mechanism and anti-trafficking. Why wouldn’t that work? On the same note, if a patient has done well with an anti-TNF for a while, we can pivot to another therapy. But you know they do respond to that drug class. If they develop antibodies and lose response, it makes sense to go to that same class where we know something works. It’s nice that we have these options, but it brings up important sequencing questions.

Douglas Wolf, MD: The immune system is very complicated. It’s difficult to predict the right sequencing. I have a few patients who were primary failures with vedolizumab and then went into remission on ozanimod. It’s hard to predict. The bottom line is that we don’t have true predictors…. We’re fortunate that we have more class options to try in this difficult disease.

David Hudesman, MD: That’s a great point. Let’s pivot to Crohn disease. We have ozanimod and upadacitinib as new or small molecules for ulcerative colitis. For Crohn disease, our newest agent is risankizumab, a selective IL-23 inhibitor. Doug, maybe you could touch on the data, how you’re using this agent in your practice, and how you’re incorporating it in your sequencing.

Douglas Wolf, MD: Risankizumab is a great option when a biologic is needed for Crohn disease. It’s more selective than the IL-12/23 agents. That may lead to an advantage. I don’t think we know at this point. But this agent is very well tolerated. The 3 IV infusions that are used to provide induction therapy are incredibly effective at providing a response and a remission by the end of induction. The IV induction and subcutaneous maintenance strategy that’s been designed for this agent is excellent and a great option.

Jordan Axelrad, MD, MPH: Dave, tell us how you’re choosing the right sequencing of therapies in Crohn disease and how you’d manage a moderate vs severe patient differently.

David Hudesman, MD: With risankizumab, I agree with everything Doug showed. There are some nice efficacy data showing the difference between drug and placebo, which we haven’t seen as much in other patients with Crohn disease. Once you’re first vs second vs third line, a lot of times we see that dip, but with risankizumab there’s still a persistent difference between drug and placebo when you go first, second, or third line. It’s a very effective agent. How do I position it along that moderate-to-severe spectrum? In more moderate patients, before risankizumab, I used a lot more ustekinumab in the first line. I’m starting to transition that to risankizumab. It hasn’t been on the market for long, so I need some more real-world experience. I’ve been using that more as the first-line agent, but in uncomplicated Crohn, I’ve seen efficacy in the second line. With Crohn, if there’s anything that concerns me—significant small bowel disease, significant deep ileal ulceration, perianal disease—I stick with anti-TNF. I’m still using a good amount of anti-TNF in the first, second, and third lines, mostly infliximab and adalimumab. I’m seeing risankizumab used more in Crohn, but if anything concerns me, I lean on the anti-TNF.

Jordan Axelrad, MD, MPH: Doug, how you think about patients who are refractory to ustekinumab? Is that a patient for whom you’d consider risankizumab after? How are you evaluating that?

Douglas Wolf, MD: Good question. I’ve used risankizumab in the bio-naïve and the multibiologic failure Crohn populations, including those who’ve apparently lost response to ustekinumab. There have been benefits. That’s been seen in the clinical trials, and I’ve seen it in clinical practice. It’s different enough from all the others that it’s a go-to agent when you need it for what one might term as salvage or simply another option. It’s effective.

David Hudesman, MD: You brought up an interesting point about the comparison between ustekinumab and risankizumab, and we’ll have further head-to-head studies. We don’t have them yet for IBD, but if you look at psoriasis, the selective IL-23 inhibitor outperformed ustekinumab. There are some phase 2 data, with a different IL-23 inhibitor guselkumab [Tremfya] looking at ulcerative colitis. Maybe there was a trend toward better healing. This is something that will be interesting in terms of efficacy. Is there a difference? We don’t know, but this is another very safe agent, and we’re comfortable with that.

Jordan Axelrad, MD, MPH: The class of IL-23 inhibitors is going to be a growing class in our field, as it has been in other immune-mediated disease states.

David Hudesman, MD: Let’s pivot to something that’s going to impact all our practices and will probably be a headache: biosimilars, biosimilar adalimumab [Humira], and others coming to market. What are your thoughts on biosimilars? Does anything concern you about the use of them? Right now we have infliximab and adalimumab biosimilars.

Douglas Wolf, MD: Biosimilars do add an option for treatment. It’s not a class alternative. If one hasn’t benefited from the reference or originator agent, one isn’t likely going to benefit from the biosimilar. The reason they’re out there and that the government has backed this is the hope that it will bring down prices of biologic anti-TNF and other agents as they come out. Whether this is true, I’m not sure. I don’t know if it reduces cost for patients, but that’s a consideration. They don’t have the same access systems to provide free drugs to indigent patients, but that’s an alternative. Insurance companies have basically mandated switches to biosimilars. The challenge with an infliximab is that 1 year a patient switches to 1 biosimilar, and then another year they may be switched to another. No facility, whether it’s a hospital or a practice, can stock more than 1 or 2 of these agents. In the past we were able to manage and monitor these patients well in our infusion units. Now we need to farm them out to sites that can give a particular biosimilar agent. That wasn’t anticipated, but it’s a challenge to all our practices.

Jordan Axelrad, MD, MPH: The new learning curve with adalimumab biosimilars is that there are going to be many new devices. Our patients, our staff, and we are going to have to be familiar with multiple different devices and how they should be utilized and stored. It’s going to be a steep learning curve, especially because adalimumab is able to be swapped out at the pharmacy. We may not know if patients are getting an originator vs a biosimilar that their individual policy covers.

David Hudesman, MD: It’s important that we learn from one another about how to incorporate this into our practice. That’s exactly my biggest concern. There have been multiple studies—infliximab, adalimumab, different disease states. I’m not worried about efficacy or safety or drug levels, antibodies, or anything like that. How do you use it in practice? Is the patient aware? We’ve learned from this that when we used infliximab, the patient came to an infusion center, and sometimes they found out that day that they were getting the biosimilar before they heard from us when it first came out. That’s not the way you want to do that. There’s a lot of concern and anxiety, and the key is education, having the staff communicate with the patients, letting them know ahead of time, determining the right workflow. For me, that’s the biggest concern.

We’ve had a great discussion about how we’re positioning therapy, how we’re sequencing therapy, and how we’re incorporating some of our newer agents. Maybe we could go around and ask each of you what you’re most excited about in the next couple of years, whether that’s newer therapies or different uses of our current therapies. Doug, let’s start with you.

Douglas Wolf, MD: There are 2 areas. One is whether monotherapy with anti-TNF and infliximab is best, or whether it’s a combination therapy. I use monotherapy the most because I’ve seen the most severe complications, primarily lymphoma associated with combination therapy and immunomodulators, especially 6-MP [6-mercaptopurine] and azathioprine [Imuran]. We’re still sorting that out. The other topic is combination biologics. I’ve been involved in a couple of clinical trials that used them with efficacy and safety. That may be the better way to add a second agent in the moderate or severe disease severity category, when you really need the best combination for your patients. The challenge is getting an insurer to pay for it. We’ve been successful selectively in using it, but the majority of cases have resulted in denial. I don’t know how things have worked in your facility.

Jordan Axelrad, MD, MPH: Doug, you alluded to part of it. These combination biologic studies are very intriguing, especially for our sick, complicated patients. What we’ve learned from some of those studies, particularly in Crohn disease, is that arms that included an IL-23 agent, even a monotherapy, was effective. I look forward to moving forward better utilization of different IL-23 agents and how that class may help our patients. Combination therapy looks better, but how that can be done is a question.

David Hudesman, MD: For most of the patients I have on it, there’s an EIM [extraintestinal manifestation]. You have 2 reasons to use it, and that’s how we’ve been able to get it through. Otherwise, we’re not there yet for prime time. Should we be using this up front? Should they fail 1 agent? Should they fail multiple agents? As you said, you’ve been involved with a lot of ongoing studies. That’s the most exciting part. There are newer agents coming to market and this concept of companion diagnostics. We don’t have the full data on that, but maybe can we personalize therapy or at least say, “You’re more likely to respond to this class if you test positive here.” We’re not there yet, but there are some interesting early data on that.

I want to thank everybody for their time. This is a great discussion. The last key point is that whatever agents we’re choosing for our patients, let’s start these therapies early. If we start early, we tend to have better results. Thank you so much, Doug. It’s great seeing you. Great speaking to you Jordan.

Douglas Wolf, MD: Thank you, David. Thank you, Jordan, I appreciate this dialogue.

David Hudesman, MD: Jordan, that was a great discussion with Doug talking about our newer therapies. But I want to nail this down a little. If a patient with moderate to severe ulcerative colitis presents to your office, what does that discussion look like with that patient to pick that first-line therapy?

Jordan Axelrad, MD, MPH: For moderate to severe ulcerative colitis, more with the moderate spectrum patient, I’m thinking about vedolizumab and ozanimod as first-line therapies. A lot of that conversation centers on how the patient wants to take their therapy. Vedolizumab is infusion; ozanimod is oral. Those are important considerations. But with ozanimod, we don’t have a lot of data in women who become pregnant. Those are the major considerations in drug selection, but it’s vedolizumab and ozanimod. Did they think about first line for patients with more moderate ulcerative colitis? Although ustekinumab is sometimes a little difficult to use in the first line, that’s also a decent option to consider.

David Hudesman, MD: Is safety driving that decision for you? Why that vs infliximab?

Jordan Axelrad, MD, MPH: For me, safety considerations are important, but they’re secondary to efficacy and mode of administration factors. I tend to reserve infliximab for sicker patients. Even though it’s important that we use the most effective therapy up front and early, sometimes it’s important to reserve infliximab for the sickest patients. If a patient fits more moderate criteria, they’re a good candidate for other therapies. This way, if they flare or their disease extends, you can always have infliximab ready to use in your pocket. I tend to use that for severe patients. I don’t use adalimumab as much in my ulcerative colitis practice, especially given head-to-head data that it’s maybe not as good as some of our other agents. But I use infliximab for a patient with severe ulcerative colitis.

David Hudesman, MD: I agree completely. Let’s say you start your patient on ozanimod. How are you monitoring this patient? Doug mentioned calprotectin. At what point do you ask, “Is this patient doing well? Do we give the therapy more time?”

Jordan Axelrad, MD, MPH: We’re typically waiting the full induction period to assess whether patients are going to respond. We’ve seen data—particularly in the oral small molecule class, but in other classes as well—that patients who respond earlier have a little noticeable change in their symptoms and even biomarkers within that first 2 weeks. These patients tend to respond best over time. If patients are getting nothing out of the drug after 8 weeks or so, that’s where you start to think about whether this drug is going to work. If patients are failing earlier, you’re going to make intervention soon. You’re not going to have them suffer for 8 weeks of therapy. There are some data, however—this is more in the JAK inhibitor class—that even up to week 16, patients can start to get better response. Even if you continue therapy longer without that full robust response, you can capture some patients with more time. That has to be balanced with how patients are feeling and whether they can tolerate that full latency to get to week 16. You want to see something early, but often we need to wait a little longer.

David Hudesman, MD: That’s a great point. I was going to bring that up. You have that delayed response. You have patients who do well early. We see this with those ozanimod. By week 10, certain patients didn’t respond. By week 15 or 20, you’re capturing another 30%. That’s similar to what we see with upadacitinib and tofacitinib.

Jordan Axelrad, MD, MPH: What’s important is that you need to assess what that response is. You need to chat with the patient. You should be checking labs and biomarkers to assess whether a drug is helping.

David Hudesman, MD: If the symptoms are improving within a couple of months, and there’s no movement in the CRP or calprotectin, it’s hard to keep giving that more time. It depends on the severity of the patient. If you have a sicker patient, you’re not going to keep that going. What about colonoscopies? When are you scoping patients with ulcerative colitis? Does it need to be perfect? Is better or good enough? What are your thoughts on that?

Jordan Axelrad, MD, MPH: Perfection is what we’re striving for but hardly achieving. For ulcerative colitis, I’m usually rescoping patients 6 or 7 months after initiating therapy. In Crohn disease, we may push that out a little more—it’s more transmural, it has more complications, it may take more time to get that full response endoscopically. What I’m looking for is improvement. Normality—a complete remission endoscopically—is a difficult benchmark to achieve for many patients. That endoscopic improvement is good enough to suggest that the drug is working and we should continue on. We may think about optimizing things if we want to improve that even more, but not having normality is OK.

David Hudesman, MD: I agree completely. If we see it and it’s great, we’re all very happy. The patient is very happy. But if it’s improving and everything is moving in the right direction, that’s the wrong time to pivot. I agree with optimizing. I’m seeing more patients with ulcerative colitis who get a 6-, 7-month colonoscopy. They’re a lot better. The next time you scope them, there’s continued improvement. It might not even be pushing more drugs; it’s giving things more time. With Crohn disease, we have newer agents. How much TNF are you still using? Are you starting to say, “I’ll hold that TNF for a sicker patient,” as you mentioned for ulcerative colitis? Or is Crohn a little different?

Jordan Axelrad, MD, MPH: Crohn is a little different. Anti-TNF therapies are very effective in Crohn if they’re used early to prevent some of those complications, like structuring and fistulizing disease. For many of our patients, anti-TNF is a very good therapy. We’re obviously learning more about the IL-23 class, which has some data suggesting that this drug may be very effective over time as you get cumulative benefit. We’re learning more about that. In my practice, I’m still using a lot of anti-TNF for those at risk or who already have complications, such as structuring or fistulizing disease.

David Hudesman, MD: I agree completely. We need to talk about that point more over time. If you’re speaking with patients and they have a first-line therapy, they want to get better quickly and we want them to get better quickly. It might be their first agent. If they lose response, then it’s their second agent. Durability of therapy is important. That’s where some of our newer agents like the IL-23s might hold an edge.

Jordan Axelrad, MD, MPH: I agree completely. You talk about durability and switching therapies, which is also important. Even though we have more options, we still don’t have many options. Before you turn to a different drug or different class, it’s important to recognize whether the patient is truly refractory to this drug before moving on.

David Hudesman, MD: That’s great. This has been great discussion. Thanks again.

Jordan Axelrad, MD, MPH: Thanks, Dave.

Transcript Edited for Clarity