AUDIO TRANSCRIPT

Susan: Diagnosing IBS-D can be a challenge. Then treatment can require patience and determination.  I'm Susan Brazil. On this episode of IBS-D Decoded, we meet the experts.

Susan: First up, someone who approaches IBS-D with a well-rounded perspective.  Dr. Brooks Cash has been both a researcher in the field of IBS-D and has also treated many patients.  Dr. Cash, thanks for joining us.

Dr. Cash: Thanks so much for having me, Susan.

Susan: Could you please share some of your background, Dr. Cash?

Dr. Cash: I attended medical school actually in the military. I was a finance major and undergraduate, and I learned in my undergraduate degree at the University of Texas that I didn't want debt. And so I was able to get a debt-free medical education and all I had to give the military was another 20 years of my life. And I also completed my training at Bethesda Naval Hospital also known as, at the time, the National Naval Medical Center in Internal Medicine. And my fellowship in gastroenterology during my fellowship, I recognized that there was a real unmet need for patients with what we called at the time, functional GI disorders and included in that is irritable bowel syndrome. I recognize that that was a huge void in our knowledge base, our understanding, our management of patients with chronic gastrointestinal conditions. And also recognize that there were some real opportunities there to help patients. And at the time that I was training, which was 25-30 years ago now, we didn't have a lot of therapies for this condition. And we also didn't quite know how to diagnose this condition. And it was often a diagnosis of exclusion. And to me, making a diagnosis based on a whole bunch of negative tests was intuitively unattractive. So most of my research in this field has centered around trying to come up with a common sense, expeditious and patient friendly way that is still accurate to diagnose irritable bowel syndrome. I've also done quite a bit of research with merging and developing therapies in this field as well. I was born and raised in Houston, Texas. And now I'm the Chief of Gastroenterology, Hepatology and Nutrition at the University of Texas Health Science Center in Houston at the Texas Medical Center.

Susan: Let's start with some of that research. What has it taught you about properly diagnosing IBS-D?

Dr. Cash: Well, a diagnosis of IBS-D begins with identifying chronic recurrent symptoms of abdominal pain associated with diarrhea and by performing a careful history, physical exam and limited laboratory tests. The 2021 American College of Gastroenterology Guideline recommends a positive diagnostic strategy over a diagnosis of exclusion for patients with symptoms of IBS-D as it improves the time it takes to initiate appropriate therapy. So in the absence of secondary causes or alarm features such as anemia or blood in the stool, weight loss, typically more than 10 pounds, fever, recent illness, medications, symptom onset over the age of 50 or a family history of colorectal cancer, abdominal mass or other organic gastrointestinal disease, we feel that you can make the diagnosis based on symptom based criteria. And we use what are called the Rome Criteria for IBS, with diarrhea.  And we can make that diagnosis with minimal, further testing.

Susan: What are some of the specific symptoms that you're looking for when diagnosing IBS-D?

Dr. Cash: That's a great question. And I mentioned the Rome Criteria.  We're now on the Rome four criteria or the fourth version of these criteria and in those criteria, IBS is defined as recurrent abdominal pain lasting on average, at least one day a week in the last three months.  And it's associated with at least two of the following features: defecation related, a change in the stool frequency, or change in the stool form. These criteria should be fulfilled for the last three months with symptom onset six months before diagnosis. And for IBS with diarrhea, or IBS-D, this is related to the diarrhea so over a quarter of the patient's bowel movements are Bristol stool form scale types six or seven, that correlates to mushy or watery stools, and less than a quarter of the stools are types one or two, which are what we call scybalous or like rabbit pellet stools, or hard and lumpy stools. Now there may be other symptoms such as bloating, but those aren't required to fulfill the criteria.

Susan: Diarrhea and abdominal pain and bloating, usually aren't life-threatening but they can certainly be impactful.  Tell us about the patients who present with these symptoms.  Some of them must be frustrated.

Dr. Cash: You know, all of them are frustrated. The chronicity of the symptoms, the recurrent and unpredictable nature of the symptoms and the impact on our patient's quality of lives leads to a lot of frustration for them.

Susan: Dr. Cash, you've treated lots of IBS-D patients. How do you get them to open up to you by their symptoms during that first visit?  Is that difficult sometimes?¹

Dr. Cash: It absolutely can be. You know, this is for some patients a very embarrassing topic to discuss. First and foremost, I ask patients to describe their symptoms to me in their own words. I try to avoid going through a checklist of symptoms that they simply answer yes or no to. I want to hear what their experience is. And I also want to get an idea of how their symptoms are impacting their lives. The second thing that I try to do is I try to maintain a very open body language and make good eye contact. And then I try to educate patients about irritable bowel syndrome with diarrhea.  What the prevalence is, it's been estimated between about 5-10% of the population is affected by irritable bowel syndrome. So I'm trying to convey to them that they're in good company, they're not alone and that we have some good options for their evaluation and treatment.²

Susan: Are there over the counter medications that a patient can try?

Dr. Cash: There are over the counter medications that most of our patients by the time they get to see me in a specialty office or a subspecialty office like GI, have tried, this includes pain medications, as well as antidiarrheal medications.The issues that many patients have with over the counter therapies are that any relief that they get is often temporary and it's not a long-term solution. There's also some potential for some adverse effects like constipation or even worsening abdominal discomfort for some patients. I tend to ask my patients what they've used over the counter because I want to get an idea of what steps they've taken. I also asked them about lifestyle modifications. And then typically if those haven't been satisfactory for them, we'll move on to prescription therapies.

Susan: What causes IBS-D? What does the research say about that?

Dr. Cash: While food and stress can often trigger IBS-D symptoms, there's more to this story. Now, the exact causes of IBS-D are unclear, but experts believe that a few factors may be involved and these factors have to do with changes in gut motility, as well as changes in gut sensation. We believe that these changes are arising at the level of the muscles in the gastrointestinal tract, and they may contract too much. There's also changes with regards to the nerves in the bowel that may not respond as they should. And there can be changes with regards to signals communicating between the bowel and the brain or the central nervous system that may be disrupted.

Susan: Knowing some of the root causes of IBS-D, let's talk about possible long-term treatments.

Dr. Cash: Well, the good news for these patients is that there are more treatment options than there were just a few years ago. One of the prescription treatments that can help patients be proactive against IBS- D is VIBERZI.  VIBERZI, also known as eluxadoline, is indicated in adults for the treatment of irritable bowel syndrome with diarrhea.  Now here are a few safety considerations. VIBERZI is contraindicated in patients without a gallbladder or in patients with known or suspected biliary duct obstruction or sphincter of Oddi disease or dysfunction, a history of pancreatitis or structural diseases of the pancreas. It's also contraindicated in patients with alcoholism, alcohol abuse, alcohol addiction or who drink more than three alcoholic beverages per day. VIBERZI is also contraindicated in patients with a known hypersensitivity reaction to VIBERZI or those with severe hepatic impairment and finally, in those with a history of chronic or severe constipation or sequelae from constipation or known or suspected mechanical gastrointestinal obstruction.

Susan: Have some IBS-D patients changed their daily habits to try to accommodate their IBS-D symptoms? Have they reluctantly accepted that they may have to live with symptoms like chronic diarrhea forever?

Dr. Cash: I think that that's a really important point that you make. Many of them have not become patients yet. We talked about the over the counter therapies. They're quite accessible for people to use. And when I see individuals in my clinic complaining of IBS-D symptoms, almost universally they've tried those therapies. The other things that they'll do is they'll change their lifestyles. They changed their diets dramatically often without a lot of great evidence to support what they're doing. I have patients that I've talked to that will drive a certain route to work or school because they know the bathrooms are clean along the way. They plan their days very carefully. They can't leave the house until they've had a certain number of bowel movements. The changes that people make to accommodate their symptoms of IBS-D can be quite dramatic.

Susan: Helping find a solution that may work for them must be very rewarding for you.

Dr. Cash: I can't stress how good it makes me feel to help patients with this condition. It's absolutely rewarding and it really does make the efforts all worthwhile.

Susan: We have a patient that I'd like for you to hear about in our next episode. Dr. Cash, we really appreciate you being willing to help others by telling your story. Thank you.

Dr. Cash: Thank you very much.

Susan: You met our next expert in episode one. Welcome back, Dr. Sayuk.

Dr. Sayuk: Thanks, Susan. I'm glad to be here.

Susan: I just spoke with Dr. Cash about VIBERZI as a treatment option. Before we talk about who would be good candidates for VIBERZI, who is definitely not a candidate for VIBERZI?

Dr. Sayuk: Well, one particular group of patients that is not a candidate for VIBERZI are individuals who have undergone a cholecystectomy, or who have had their gallbladder removed.

Susan: Is that common?

Dr. Sayuk: Well, in some cases, patients may have had symptoms that were misconstrued by their providers as being due to an abnormality or a dysfunction of their gallbladder. And so ultimately they ended up undergoing a removal of their gallbladder to try to improve the symptoms for that individual.

Susan: What's the recommended dosage of VIBERZI? Do you tell patients to take it daily? Or?

Dr. Sayuk: Well, there are two doses. There's a 75 milligram dose and a 100 milligram dose. In both cases, the medication is taken twice daily with food. And in the majority of cases we start the 100 milligram dose as the typical dose for a patient to begin with.

Susan: So maybe with breakfast and dinner?

Dr. Sayuk: That's right.

Susan: How does VIBERZI work?

Dr. Sayuk: VIBERZI works on the opioid receptor system in the gut as a mixed agonist and antagonist. What we believe is that by activating or blocking these opioid receptors in the GI tract, it leads to a decrease in visceral hypersensitivity. And it has effects on gut motility.

Susan: Looking at the clinical trials, what can you share about the efficacy of VIBERZI?

Dr. Sayuk: There have been two large clinical trials that were conducted to demonstrate the benefit of VIBERZI specifically in IBS-D and what these trials showed was the potential to improve, not just abdominal pain, not just diarrhea, but in a significant number of patients, the combination of both diarrhea and abdominal pain in the same individual.

These studies have also shown that these symptoms may be relieved over 12 weeks of treatment. And in many cases, when the patient who has started on VIBERZI improves, relief of both symptoms is maintained throughout the course of treatment.  In the clinical trials, compared with placebo, the proportion of patients who experienced relief of both abdominal pain and diarrhea taking VIBERZI was numerically higher as early as month 1 through month 6. 

Susan: What side effects do you look out for?

Dr. Sayuk: There are a few things that we monitor when a patient is started on VIBERZI. The most common side effects or adverse events that were documented within the clinical trials: constipation, abdominal pain and nausea.  All three of these were noted to occur at a rate of greater than 5% in the clinical trials. Practically speaking, the most important one for providers to be aware of is constipation. Because if this is to occur, typically patients will experience this within a short period of onset of use of the medication and so usually within the first two weeks, if a patient is going to experience constipation, they will after starting the medication.

Susan: All right. Let's get to the good news. If all goes well, according to the clinical trials and your observations during treatment, what's the result we're looking for by treating with VIBERZI?

Dr. Sayuk: Well, of course, no treatment offers a cure for IBS-D, but what we're hoping for in our patients that are started on VIBERZI is a potential to improve the diarrhea, as well as the abdominal pain. So in an ideal situation, they're having to use the bathroom less often, and they may notice that there's an improvement in the consistency of their stool. So their stools are no longer loose and watery, but more of a formed regular consistency.
Susan: What early signs of progress do you hope to see in a patient?

Dr. Sayuk: We typically observe benefit within 30 days if the patient is going to get a good response to the medication. What we tell our patients that are starting on VIBERZI is give it a month, give it 30 days to see if you notice a meaningful improvement in your diarrhea, in your abdominal pain. And that will be a good indication to us that VIBERZI may be a good option for them to manage their symptoms in the longer term.

Susan: In our third episode, we're going to talk with a patient who's been dealing with IBS-D for a very long time.  I'd really like for you to hear her story, Dr. Sayuk.

Dr. Sayuk: I look forward to it.  Thank you.

Susan: Thank you. Right now though, let’s review the important safety information.

Announcer Jacent: VIBERZI, or eluxadoline, a schedule 4 controlled substance, is indicated in adults for the treatment of irritable bowel syndrome with diarrhea, IBS-D.

VIBERZI is contraindicated in patients without a gallbladder; with known or suspected biliary duct obstruction, or sphincter of Oddi disease or dysfunction, a history of pancreatitis, or structural diseases of the pancreas. VIBERZI is contraindicated in patients with alcoholism, alcohol abuse, alcohol addiction, or who drink more than 3 alcoholic beverages per day; patients with a known hypersensitivity reaction to VIBERZI; those with severe hepatic impairment; and in patients with a history of chronic or severe constipation or sequelae from constipation, or known or suspected mechanical gastrointestinal obstruction.

Pancreatitis, with or without sphincter of Oddi spasm, has been reported in patients taking either the 75 milligram or 100 milligram dosage of VIBERZI, including serious cases resulting in hospitalization, primarily in patients without a gallbladder. Fatal cases have also been reported in patients without a gallbladder. VIBERZI is contraindicated in patients without a gallbladder.  Most of the reported cases of serious pancreatitis occurred within a week of starting treatment with VIBERZI and some patients developed symptoms after one to two doses. In patients with a gallbladder, evaluate a patient’s alcohol intake prior to starting VIBERZI. Instruct patients to avoid chronic or acute excessive alcohol use while taking VIBERZI. Monitor for new or worsening abdominal pain that may radiate to the back or shoulder, with or without nausea and vomiting. Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of pancreatitis such as acute abdominal or epigastric pain radiating to the back or shoulder associated with elevations of pancreatic enzymes with or without nausea and vomiting. There is a risk of sphincter of Oddi spasm, resulting in pancreatitis or hepatic enzyme elevation associated with acute abdominal pain (for example, biliary-type pain) in patients taking VIBERZI. Serious adverse reactions of sphincter of Oddi spasm with or without pancreatitis resulting in hospitalization have been reported, primarily in patients without a gallbladder. Cases of serious sphincter of Oddi spasm occurred within a week of starting treatment with VIBERZI and some patients developed symptoms after one to two doses. Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of sphincter of Oddi spasm such as acute worsening of abdominal pain that may radiate to the back or shoulder with or without nausea and vomiting, associated with elevations of pancreatic enzymes or liver transaminases. Do not restart VIBERZI in patients who developed biliary duct obstruction while taking VIBERZI.  In postmarketing experience, serious hypersensitivity reactions (including anaphylaxis) have been reported following VIBERZI administration. Some of these reactions occurred after the first one or two doses of VIBERZI. Instruct patients to immediately stop VIBERZI and seek medical attention if they experience symptoms suggestive of a hypersensitivity reaction. Constipation, sometimes requiring hospitalization, has been reported following VIBERZI administration. In postmarketing experience, severe cases with development of intestinal obstruction, intestinal perforation, and fecal impaction, requiring intervention, have also been reported. Instruct patients to stop VIBERZI and immediately contact their healthcare provider if they experience severe constipation. Avoid use with other drugs that may cause constipation. The most commonly reported adverse reactions (incidence >5% and greater than placebo) were constipation, nausea, and abdominal pain.

To learn more, please see the full prescribing information at the link provided or visit www.rxabbvie.com/pdf/viberzi_pi.pdf.

Susan: Also in episode three, we'll meet a young man who started experiencing the symptoms of IBS-D when he was in college. And we'll check in again with patient, Molly, who has some important advice for healthcare providers.  There's more information about IBS-D and VIBERZI for healthcare providers on VIBERZIhcp.com including how some patients may qualify for the VIBERZI savings program. I'm Susan Brazil, thanks for listening to IBS-D Decoded.