In the setting of irritable bowel syndrome with diarrhea (IBS-D), key opinion leaders reflect on the role of eluxadoline.
Mark Pimentel, MD: Let’s switch gears. Let’s talk about eluxadoline. Bill, you have some experience with the product but also, perhaps, in the clinical trial work. What’s your thought on eluxadoline? Tell us about the product, first, and then the post-product experience and some of the adverse effects.
William D. Chey, MD: Eluxadoline is a drug that affects different types of opioid receptors. Like loperamide, it’s a mu opioid agonist. But it also has effects on delta and kappa receptors as well. So this mixed agonist/antagonist activity is thought to decrease the likelihood of developing tolerance and also enhance the effects on pain. There was evidence in the phase 3 trials, which Tony published, on the overall symptoms—pain and diarrhea in patients with IBS-D [irritable bowel syndrome with diarrhea]. As you alluded to, it’s FDA approved, and there are 2 doses, 75 mg and 100 mg, taken twice a day. Overall, I think it’s a very effective drug, particularly for diarrhea. I think it can be very, very effective. The 1 issue that people need to know about: Just as we talked about safety issues around alosetron, with eluxadoline there is a risk of developing abdominal pain and elevated liver enzymes or pancreatic enzymes thought to represent either sphincter of Oddi dysfunction or acute pancreatitis.
It’s interesting. I saw a poster here, at this meeting, talking about the postmarketing experience, which is actually describing a sharp reduction in the report of cases of sphincter of Oddi dysfunction, acute pancreatitis, which is encouraging.
Mark Pimentel, MD: But isn’t that because of the warnings that were posted by the FDA?
William D. Chey, MD: Yeah, but to me that’s great.
Mark Pimentel, MD: That’s what the FDA is for—monitoring.
William D. Chey, MD: That’s exactly what we had hoped for, right? And just to amplify that point, the people listening to the program should just understand that you should not be using this drug in people who have had a cholecystectomy, because those are the people who are more likely to go on and develop sphincter of Oddi dysfunction with this drug. And you should not be giving this drug to people who are consuming more than 3 alcoholic beverages per day, because that seems to amplify the risk for developing acute pancreatitis. But you’re absolutely right about the comment about that data. It’s very encouraging that the rates are going down with people being more circumspect to following the instructions laid out by FDA.
Mark Pimentel, MD: It’s important to follow the safety guidelines on products. Your experience with eluxadoline, Tony?
Anthony J. Lembo, MD: Sure. I think what Bill said is correct. In the clinical trials, data show that it seems to have more effect on bowel function, less so with abdominal pain. Just 1 caveat: When you look at the cutoffs for abdominal pain that were used in that trial, like improvement of more than 30%, which is thought to be clinically significant, it was not statistically significant in the trial. But when you used a higher cutoff, like 40% or 50%, you did see more separation. And the placebo response rate was quite high. In the phase 3 trials, it was about 50-plus percent of patients who had an improvement of 30% or more, but the placebo rate was right on its tail, which is pretty high for a clinical trial. But I think it does mirror my clinical practice as more of a bowel function...
William D. Chey, MD: Mark, may I just make 1 more comment on that?
Mark Pimentel, MD: Yeah, sure.
William D. Chey, MD: Tony was involved in this project as well, but it’s also important to mention that for patients who have not responded to loperamide, eluxadoline can still work. Because the reality is that we’re never going to use this drug as a first-line agent. You’re only going to use this in people who have failed other things, like loperamide, in particular. And it turns out that there still appears to be efficacy in people who have not gotten better with loperamide by using eluxadoline. So I just wanted to mention that for the folks who are listening.