Experts in gastroenterology discuss their approach to sequencing therapies in ulcerative colitis, considering safety, efficacy, and access to various treatment regimens and comment on challenges physicians may face when incorporating new therapies into clinical practice.
Miguel Regueiro, MD: Dave, let’s get into how you sequence therapies, especially for safety and efficacy. How do you sequence therapies in ulcerative colitis [UC]?
David P. Hudesman, MD: Sure, and Marla said this nicely. Patients are concerned about safety from their viewpoint, but for me, when I start, it must be about efficacy. Now we have options. It doesn’t matter how safe a drug is, if it doesn’t work, it’s irrelevant. The way I break it down is, we have the moderate to severe spectrum, ones on the more moderate end, and then we have our sicker, severe patients, who could be hospitalized, on high dose steroids. In those more severe patients, I’m using infliximab or a JAK inhibitor and likely upadacitinib. The majority of the patients we’re seeing are in this more moderate to severe end. From that point, all of our therapies are reasonable options.
Then the next thing we can talk about is safety. Why not start with something that’s more targeted, which would minimize the safety adverse effects? We talk about vedolizumab, ustekinumab, and ozanimod in my practice. We’re going to need more real-world data for ozanimod, but practically they’re all safe, and we don’t see many adverse effects with any of these agents. Then it becomes onset of action, which we talked about. Do you want an infusion every 8 weeks vs an injection every 8 weeks vs a pill once a day? That’s where that shared decision-making comes in. The only other thing to add is that extraintestinal manifestations can shift you to a more systemic therapy.
Miguel Regueiro, MD: Very nice, Dave, thanks for that. Ellen, what is your position on therapies and sequencing? Then Marla, I’m going to come with the same question, and what are the challenges that our physicians and colleagues might face in incorporating these new therapies? Ellen, how do you sequence and position in ulcerative colitis?
Ellen J. Scherl, MD: The first thing is to try to get them off the mesalamines, or onto something better sooner rather than later; the same thing with steroids, limit the use. I have been using first-line vedolizumab or ustekinumab, as opposed to the anti-TNF [tumor necrosis factor therapy], with the exception of the patient who’s looking at a colectomy and hospitalization. We go for IV [intravenous] cyclophosphamide or infliximab for time of onset and dose escalation. But in the more moderate to severe, it’s going to be vedolizumab. Based on the VARSITY trial, we’re talking about superiority at week 52, 31% steroid-free compared to 22% with adalimumab. That’s the first-line discussion. Then as David alluded to, it’s a discussion about ease of use, time in an infusion suite or at home. Similarly, with ustekinumab, these don’t have black box warnings around them, so not only are they effective, at least VARSITY—more effective than adalimumab—but the safety issue. No black box around either vedolizumab, ustekinumab, or Zeposia [ozanimod]. Ustekinumab has been my second choice for first-line therapy rather than a TNF. We look at the UNIFI data long-term steroid-sparing, years out, 4-year data just being presented. It is more targeted, not all lymphocytes, just a subpopulation of lymphocytes, the dendritic cell targeting IL [interleukin]-12/23.
Ozanimod in the first line is increasingly attractive. You’ve put this on the line, that it is safer than patients’ concerns. Yes, we can get a cardiogram, but it’s in a very select group of patients. In the original trials, there was a 5-hour observation after every pill, and within months there’s no safety signal. Real-world data are also going to show no safety issues for a cardiogram. Ophthalmologic exam, it’s a subpopulation, and patients with steroids are at an increased risk for ophthalmologic glaucoma, cataracts, than patients on ozanimod. It’s very important that those are the first 3 medications. We look to JAK inhibitors, they’re not yet approved for the first line. But in select patients who are more severe, we might want to use those as first line. Again, steroid-sparing strategies is the way that I position all of this.
Miguel Regueiro, MD: Wonderful, that’s great. Marla, let’s move to you in terms of anything else with sequencing, and as you hear from colleagues who refer patients to you, what are the challenges? Are they facing challenges with prescribing some of the newer therapies?
Marla Dubinsky, MD: Yes, believe it or not, I thought we would have a much harder time prescribing some of the new oral small molecules, and I haven’t encountered such an issue as much as I thought. Maybe because, for example, ozanimod is already approved for relapsing MS [multiple sclerosis], and upadacitinib was already approved for RA [rheumatoid arthritis] and atopic dermatitis. As you see multiple indications for a certain drug, it helps us. As long as the specialty pharmacy turned on the toggle for UC, it wasn’t as much as an issue as I thought. You must also remember that when you’re switching to orals from an IV, you’re talking medical benefit vs pharmacy benefit, they are 2 different operations. It’s about understanding what these drugs are indicated for in other disease states to help you along.
Miguel Regueiro, MD: When I bring up specialty pharmacy, I realize that some of our tertiary and quaternary centers have IBD [inflammatory bowel disease] pharmacists. When we think of the challenges, especially those in the community or regional areas, sometimes it is hard to prescribe these, based on the insurance and the payer. You all mentioned with the JAK inhibitors, there must be failure of a TNF. You mentioned that we might want to use that first line, and all the reasons we outlined, but sometimes it’s difficult to get new therapies where you are regionally, based on the insurance and the payer. Hopefully, and as we evolve over time, that will get better.
Transcript Edited for Clarity