Dr Horst reviews treatment options for patients with ulcerative colitis for whom multiple biologic treatments have failed.

Sara Horst, MD, is a gastroenterologist with Vanderbilt University Medical Center who specializes in treating patients with inflammatory bowel disease.

TRANSCRIPT
I'm Sarah Horst, a Gastroenterologist at Vanderbilt University Medical Center, who specializes in the care of patients with IBD. This year I'm speaking at DDW at about a really great topic. This is, Ulcerative Colitis: Still Hot After Three Biologics, What To Do Next. These are patients that I see in clinic, in my tertiary care referral center. This was a great talk, very practical, and I was excited to go through the case, which was one of my patients that I'd seen in clinic. He's had a history of UC for five years and has failed azathioprine and infliximab, vedolizomab, and secukinumab, and I'm meeting him for the first time.

I talk about in my talk... I think one of the really important things to think about with ulcerative colitis is risk stratification. You don't just think about the person sitting right in front of you at that moment, but you think about them in their whole picture. This guy has actually a lot of poor prognostic signs and factors for severe ulcerative colitis that could lead to a colectomy. He's less than 40, he has extensive colitis. When I spoke to him, he had severe endoscopic disease. In the past he'd been hospitalized for colitis. When I met him he had an elevated CRP and even a low albumin.

The number of risk factors that patients have, the more likely they're going to be to go to colectomy. I think one of the really important keys for my talk was to remember that colectomy is a safe and effective treatment strategy for someone with moderate to severe Crohn's disease, and we need to talk about it early. I think it's important for gastroenterologists to frame this, not just as a medication failure, but counsel them that this is an actual strategy. Early involvement by a surgery team, if you think someone's at high risk for needing a colectomy, is really important because the last thing you want is that patient to be in the hospital facing a colectomy and never having heard those words.

Remember, prolonged hospitalization before a colectomy is a main predictor of postop complication, so we really need to prepare our patients. I talk to patients, we talk about colectomy, I talk about the basics and really explain what a proper colectomy with ileoanal pouch anastomosis is. That patients can have good quality of life, that an end ileostomy is also an option, and that in some studies it shows equivalent quality of life. And I go into some of the more detailed things. There is a slight increased risk of infertility in females with an ileal-pouch anal anastomosis. This is likely postoperative adhesions affecting the fallopian tubes. I think it's really important to hear it from you even before they go to see the surgeon. There's a possible lower risk by newer laparoscopic operative strategies for infertility.

If the patient does struggle with that, in vitro fertilization studies have shown there was no difference in successful pregnancy between people who had an IPAA and not. Really digging in and talking about these options with your patient, I think is number one. Then in the talk, we go through some of the newer, small molecule options that are available for patients. I talk about JAK inhibitors, tofacitinib, which actually has reasonable efficacy in patients with anti-TNF failure. When you look at the phased clinical trials, there was no real difference between all patients who were on tofacitinib versus patients who'd had anti-TNF failure.

In the longer maintenance strategy, and the longer maintenance trial patients made, the likelihood of success was higher with a higher dose. Then I talk about also the new kid on the block, upadacitinib, which is a JAK1 selective inhibitor. In the phase trials really has some good data of clinical remission at week 8 in both patients, all comers and patients, who'd had a biologic failure. So my patient--we talked through some of the risks that go along with JAK inhibitors and the importance of talking about safety and thinking about the risk of cardiac events, although very rare in the UC phase clinical trials. Slight increased risk of infection, increased risk of zoster. We talk about that in my talk.

The last thing we talk about is an S1P modulator. So, ozanimod. This is also a treatment option for patients who failed multiple biologics. There is some data to show that the more biologics the patient fails, the less likely they are to gain remission in ozanimod. But there is some data that if you can get them through a longer period of time, that lower rate goes away in maintenance. This is a good, safe drug. There are some risks with it that you have to think about as well. There is a slight risk of bradycardia. You have to really think about that patient who has cardiovascular risk factors. There's small risks of macular edema, small risk of serious infection.

In conclusion for my patient, we referred to colorectal surgery. He started a JAK inhibitor therapy. He started upadacitinib, as this was 6 to 8 months ago, and has actually been doing very well with a very slow prednisone paper. The key points are talking about surgery with your patients of a safe and effective therapy, and thinking about some newer small molecules as options.

So in conclusion, I think it's really important to talk to your patients who failed multiple biologics about colectomy, and that it is a safe and effective therapy for patients with refractory ulcerative colitis and get that surgery team involved early. JAK inhibitors are an option as well as S1P modulators as well, if the patient wants to continue medical therapy. Thanks.