The Evolving Treatment Paradigm of Irritable Bowel Syndrome


Mark Pimentel, MD: Now we shift gears to these emerging products that could be a couple of years, maybe even longer, away. But olorinab?

Anthony J. Lembo, MD: Sure. Olorinab is an interesting product that is starting in the phase 2 setting in IBS [irritable bowel syndrome] soon. It’s a timely product because it’s a cannabinoid receptor agonist. It’s a CB2. It affects the CB2 receptor, so it doesn’t have any of those psychoactive properties. What’s interesting about the product is that it seems to reduce pain, particularly in the host that is sensitized. For example, for someone with inflammatory bowel disease [IBD] and pain even though their inflammation is reduced, it seems to be effective. In IBS, there’s evidence for visceral hypersensitivity in at least a subset of patients. So it has promise. I think we’ll have to see what the data show, of course.

Brennan Spiegel, MD: To me it’s a really interesting concept. We’ve been looking for a visceral analgesic for a long time. I still don’t think we have 1. We’ve talked about a lot of medicines today that affect different aspects of abdominal pain, but this is, maybe, a new mechanism that could augment others or may unto itself be an effective visceral analgesic. But we need more data to find out.

Mark Pimentel, MD: Bill, tenapanor? We’ve heard a lot about tenapanor. Phase 3 is done. What’s happening?

William D. Chey, MD: Well, the phase 3 is completed, [as] you said. There’s been discussion about submitting a new-drug application. For people who aren’t familiar with the drug, it’s an NHE3 [sodium-hydrogen exchanger 3] antagonist. It blocks the reuptake of sodium from the small intestine and, in that way, can help with constipation-related symptoms.

Mark Pimentel, MD: So another moisturizer?

William D. Chey, MD: Yeah, but by a different mechanism. But absolutely a moisturizer, yeah.

Mark Pimentel, MD: But a lot of enthusiasm around that product. Perhaps it was because of a different mechanism? Maybe some people, as Dr Rezaie points out, respond to 1 mechanistic action of secretagogue, and maybe this was another mechanistic action. We haven’t heard a lot about what’s going on with the FDA yet, but maybe soon.

William D. Chey, MD: We’ll see. I’m cautiously optimistic. Regarding the application, we’ll see once it gets submitted and how it proceeds.

Mark Pimentel, MD: Perfect. Dr Rezaie, let’s also talk about another option, which is in phase 2 trials now.

Ali Rezaie, MD: Yes. We talked about methanogens being involved in IBS with constipation. Essentially by production of methane themselves, they can slow down the gut motility. We knew from studies in the past that statins could reduce the methanogenesis in these types of archaea. This is a nonabsorbable statin that suppresses methanogens in this archaea and potentially can improve constipation by the effect on the microbiome, which is interesting. This is another microbiome-modulating drug in the field of IBS, which is quite exciting now that we’re putting all this together. We’re finding different mechanisms of action that are being put into work to help IBS patients that, by themselves or even in combination, hopefully will help us.

Mark Pimentel, MD: Maybe even a precision medicine plan in the sense that you have a biomarker that cultivates the population that could benefit. That’s kind of an interesting thing. Now we’re going to move on to our final question, and I think this is for the entire panel. What advice do you give to the community physicians treating IBS? Let’s just go across the board here, because you’re talking to not the gastroenterologist but the doctor in the community in the trenches. Give them some hope on IBS, and give them some light that we’re trying to rule in IBS now, and to have confidence in their abilities to diagnose this. Let’s start with Dr Rezaie and move across the table.

Ali Rezaie, MD: I think the biggest thing is that first our understanding of irritable bowel syndrome in the last 20 years has been revolutionized. As we talked about dysmotility, as we talked about the microbiome and the role of diet and the different therapeutic targets that we have, it has completely changed. We should be aware of that, and we should promote awareness toward patients as well, because there’s still that stigma out there that for IBS patients that there is not much to do for IBS, and that’s not true. There are multiple treatments available, and we can help these patients move along. I think that’s the main message, in this day and age, that has changed in the last several years.

Brennan Spiegel, MD: Yeah, I agree with that as well. This stigma persists, and it’s time to end that. That’s the first thing I would say. I think many of us thought of IBS as a psychological condition that was maybe not as serious, or real, or objective as something like IBD. We talked about that earlier, and it’s time to fix that problem, first and foremost. You mentioned this earlier, Mark. Take your patient seriously, listen to what they have to say, and recognize that we now have this growing menu of options. And although it might sound like alphabet soup—plecanatide, prucalopride, and all these different treatments we’ve discussed—viewers don’t need to be an expert in every single one of these treatments. But know that they exist, and maybe become comfortable with some of them and know that there are gastroenterologists who can help viewers manage these patients proactively and meaningfully. I think it’s really time to make that switch.

Mark Pimentel, MD: Tony, anything left? These guys were hogging the answer.

Anthony J. Lembo, MD: I agree. As we’ve said, making a diagnosis early and competently. We have lots of data to suggest that we don’t need to do extensive testing. We can even now rule in IBS, but you really need to make that diagnosis early. Avoid all these unnecessary tests and procedures, and then start treating your patients. We talked about starting at the beginning, doing the lifestyle, the diet. There’s lots of evidence for diet. There’s even evidence with exercise and stress management. Start treating your patients. For those with mild symptoms, oftentimes that’s all they need. And then you progress up quickly to treatments, and we start with over the counter, depending on their bowel function, and then move into prescription treatments. We didn’t talk a lot about psychological therapies, but patients with a lot of comorbid conditions, particularly those with other chronic pain syndromes, are often the most difficult patients. But we’ll add that very quickly—the treatment. They may need to be referred to a GI [gastrointestinal] specialist or a specialty center, but do that quickly with your patients. I think you can really help them.

William D. Chey, MD: I’ve really been struck by how this whole field has evolved so quickly. We’ve talked a lot about the evolving pathophysiology and the various treatment options. From a very practical standpoint, the thing that’s really struck me is how IBS, for me, personally, has moved from being perceived as 1 of those difficult things that I can confront in the clinic to being 1 of the easiest things that I confront in the clinic now. I actually love seeing IBS patients because I have a full suite of different things that I can offer them. And I think that thinking more integratively and holistically, and understanding what your options are, makes this a very treatable group of individuals.

By the way, I recognize that in primary care, you may not have all these bells and whistles. That’s OK. Incorporate the ones that are practical for you, and your staff, and the resources that you have, but understand and utilize practices that have embraced this integrative, holistic approach. Because those are the ones that are going to lead to the best outcomes for your patients.

Mark Pimentel, MD: Well, thank you, everybody. I feel honored to have worked with you today because you’ve really provided great insights, and I respect all your opinions. This is the leadership in this field, and I’m glad that they were here. Thank you all for your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this Peer Exchange discussion to be helpful and informative.

Transcript edited for clarity.

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