Emerging Therapies for the Management of Ulcerative Colitis - Episode 5

Gaps in Ulcerative Colitis Treatment

June 18, 2021
Andres Yarur, MD, Medical College of Wisconsin

Timothy Ritter, MD, GI Alliance

Maria T. Abreu, MD, University of Miami Health System

Limitations that physicians and patients face when selecting therapy for ulcerative colitis.

Maria T. Abreu, MD: Some of the issues the treating physician and the patient face, with respect to choosing a mechanism of action, even in 2021, we don’t have good predictors yet to say, “Aha! You’re a person who’s going to respond to a JAK[Janus kinase] inhibitor,” or “You’re a person who’s going to respond to an anti-homing strategy.” I think, like I mentioned, the only comparative effect of this data that we have is vedolizumab [Entyvio] vs adalimumab [Humira]. OK, fine. But within that, I think there are nuances of picking. Sometimes they’re based on the patient profile—How risk averse are they? What age are they? Have they had other comorbidities? Have they had recurring infections?—and you might choose something, not an anti-TNF [tumor necrosis factor], for someone who’s having recurring infections. As an example, you might rethink whether you’d use tofacitinib [Xeljanz] in that scenario. But I think for medications like vedolizumab and ustekinumab [Stelara], it’s very clear that these are very safe. What about someone who has ankylosing spondylitis or other rheumatologic manifestations of their IBD [inflammatory bowel disease]? We think, in general, that when we shut off the intestinal inflammation, it’ll make the other stuff go away. But, of course, we’ve had the privilege of having something like the anti-TNFs that clearly have a salutary effect on joints and on the axial arthritidy. I think, in those scenarios, again, I might lean towards a tofa [tofacitinib] or an anti-TNF. I think that if I thought through it, these are the mechanisms that I have available. Is there something in this patient that would lead me down 1 path or when I’m making that decision?

Andres Yarur, MD: Overall, patients and physicians have several limitations when treating ulcerative colitis and these limitations have to do with the fact that even though we have many drugs available right now, a good number of patients do not respond to therapy. Also, we need to have safer medications. Even though the ones that we have right now are considered safe and we use them all the time, having an ideal adverse event profile is still far from reality. In general, improving the rate of efficacy is important not only for patients that haven’t received treatment for ulcerative colitis, but also for those that have had exposure to other biologics. An important limitation that both physicians and patients face is how we administer these drugs. Most of the drugs that are approved for ulcerative colitis require an infusion or an injection. Obviously, this is a barrier to access these drugs, especially in remote areas, and for patients who are afraid of needles and don’t want to use needles. Biologics pose other limitations, too. For example, the development of immunogenicity against the drug—in other words, the development of antibodies against the drug—especially with the anti-TNF agents. When developing immunogenicity, patients can have reactions, and the drug stops working.

Even though patients with biologics may not develop immunogenicity against the drug, many of these patients lose response to treatment and that isn’t necessarily explained by the development of antibodies.

Timothy Ritter, MD: Certainly, we’re better off now than we were several years ago when we only had 1 mechanism of action. There are several barriers to selecting treatment. Obviously, 1 of the main things that we must work with when selecting treatment is the payers. What medications are covered by insurance, and in what order. Many payers will have step-therapy. We must use the drugs in a particular order to get them approved. That is a challenge when the order is not always in-line with what you think is the best care for the patient. The drugs that we use right now, except for tofacitinib, are all perennial. They’re either infused, such as vedolizumab or infliximab [Remicade], or are subq [subcutaneous] injections, such as adalimumab or ustekinumab. Oftentimes, there are barriers to getting patients to buy into those therapies. They perceive them as invasive or scary. They worry about those, so it would be nice to have a broader armamentarium of medications with different mechanisms—many of which would be oral—that we can use to address this. Currently, there are several different mechanisms in studies that will be coming out in the future, so hopefully we’ll be able to have a lot of new options in the future for these patients.

Transcript Edited for Clarity