Emerging Therapies for the Management of Ulcerative Colitis - Episode 7

Treatment Advances in Ulcerative Colitis

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Drs Maria T. Abreu and Timothy Ritter comment on limitations faced by providers who treat patients with ulcerative colitis and highlight strategies under investigation that can improve how the disease is managed.

Timothy Ritter, MD: There are a lot of unmet needs in the management of ulcerative colitis. None of the medications that we have works all the time or maintains remission a significant amount of the time. We’re constantly trying to manage patients as they go through flares and changes in disease activity. Sometimes it can take a lot of time to find out what the best regimen is for your patients. One of the things we’re really lacking, 1 unmet need, is precision medicine. We need a tool that allows us to assess a patient that’s looking at their disease activity, their histology, their genetics, or some biomarker. We need a tool that allows us to get the right medicine the first time, which they’re doing for a lot of cancers these days. That’s coming around the course. The idea of precision medicine for inflammatory bowel disease is an unmet need.

The other thing is that we don’t have good ways to address some complications of inflammatory bowel disease. We don’t have anything we can offer patients who develop primary sclerosing cholangitis. This is a significant comorbidity in many patients. That’s also an unmet need. We need more mechanisms of actions for patients who fail current therapies. Those mechanisms, fortunately, are under development and on the way.

Maria T. Abreu, MD: Some of the things exciting me, in terms of mechanism of action, are 2 big buckets that we’ve left on the table untouched. One big bucket, of course, is the microbiome. There’s a publication in the January Gastroenterology issue on the Seres Therapeutics product, which is a clostridial species, in spore form, in a capsule. In theory, these spores survive the acid in the GI [gastrointestinal] tract and then sporulate, or start germinating, in the colon of a person with—in this case—ulcerative colitis. The study was a phase 1/2 study that was published. It’s a small study, but it has a signal. My own feeling—the FDA doesn’t ask me about my own feeling—is that some of these medications, like microbial therapy, shouldn’t necessarily be tested alone. I’d be delighted to layer microbiome therapy—with all the things you and I have discussed—as mechanisms of action because they’re going to be safe. They’re going to be safe and are going to be a fantastic addition to available treatments.

As Seres is ahead of the pack, others are going to be on their heels. For example, the epithelial barrier is another big thing that we leave up for grabs. We know that the epithelial barrier, in particular in ulcerative colitis, have holes [fenestrations] in the picket fence that contribute to the vicious cycle of inflammation. This agent is a recombinant interleukin-22. It’s an agonist. Interleukin-22 has beneficial effects on barrier function. We’ll have to wait and see because I have no intel on how well that’s doing as it winds its way in clinical trials. I suspect, and I would hope, that it’s going to be safe. Those are at least 2 things I’m excited about.

Transcript Edited for Clarity