Healio Hot Topic

Medical Management of IBS is Improving With Time

In my clinic, it still feels like we get countless referrals for irritable bowel syndrome.

We have gained so much knowledge and obtained so many new treatments in our arsenal over the years, but we are still going to need more solutions going forward if we are going to successfully serve all our patients. We need to build on this knowledge and keep making strides to ensure our patients are getting adequate care.

In the medical management of IBS, there appears to be an increasing level of understanding that the disease, particularly diarrhea-predominant IBS and mixed IBS, is a microbiome disease. That has probably been the most fruitful area of research and continues to be very exciting. Numerous abstracts and studies published over the last year that small intestinal bacterial overgrowth, for example, is a common underlying cause of IBS. New deep sequencing studies have revealed the exact organisms that might be responsible for the bloating in IBS. Other studies seem to show just how overabundant E. coli and Klebsiella are among patients with SIBO and IBS. The knowledge of those bugs and how they impact gut function and symptoms in our patients offers us new targets to explore for drug development.

Mark Pimentel, MD
Mark Pimentel

However, I think we need to be careful where we take this new information on the role of the microbiome in IBS. Specifically, I think the optimism about fecal microbiota transplant needs to go away. We now have at least five randomized controlled trials that have explored the topic, and none of the data are particularly promising. FMT has been under increasing scrutiny since a death was reported this summer. That alone should give us pause. I just hope people do not keep gravitating toward FMT for IBS.

Diagnosis

I still believe that one of the more exciting developments has been the ability to diagnose IBS. From a patient perspective, it can be easy to feel dismissed. They are told constantly that their symptoms are psychological, that it is in their heads. If they walk away from a doctor’s office without knowing what is wrong, without a diagnosis, they are not going to feel very confident in their chances of managing their disease.

We’ve been working to develop a blood test (IBS Smart, Gemelli Biotech) that has shown incredible potential. It was developed from our findings that Cytolethal distending toxin B and anti-vinculin levels are elevated in patients with IBS-D and IBS-M. We just finished a study on a second generation of the test that showed it had a specificity over 90% for either marker, and a positive predictive value of 98%. Doctors are going to use this in their practice and know, for sure, if a patient has IBS. It has the chance to be an incredibly useful tool, particularly in primary care. IBS can be a little scary in primary care because diarrhea can be caused by a lot of things. It could be celiac disease or Crohn’s disease, and it leads to a lot of unnecessary colonoscopies. This test will get us to a diagnosis faster.

In the Pipeline

Over the years, we have seen more and more pharmacological agents become available. Recently we have had two pretty exciting new additions to treat IBS-C that come from the world of prokinetics. First, is Zelnorm (tegaserod, Sloan Pharma), which is something of an old friend. It was taken off the market in 2007, but now it is back. It has been reintroduced since the FDA approved it for women younger than 65 years with IBS-C.

Even more exciting is Motegrity (prucalopride, Takeda), which is another prokinetic agent, but one that is much more potent than tegaserod. It has been shown to be highly effective for constipation. Right now, it is only approved for chronic idiopathic constipation, but I think patients with IBS-C could benefit from it.

With all of the medical therapies available for IBS-D, it is starting to feel like we are making a dent. It is still a very serious and wide-spread condition, but anecdotally, patients seem to be improving, and we are seeing less and less IBS-D in our practice. IBS-C is a different story. Constipation has been a much tougher nut to crack. Despite the numerous drugs available, we still need better therapy. We have been focusing our work on targeting methane and attempting to inhibit it. If we can find a way to get rid of that methane, maybe we can improve that subset of patients with constipation in much the same way that we help patients with IBS-D by using Xifaxan (rifaximin, Salix). However, it is likely that these therapies will take a little bit of time before they become available. If I had to guess, I would say that they will not be coming down the pipeline for another 2 to 3 years.

In the Clinic

If I see a patient who might have IBS-D or IBS-M, the first thing I’m reaching for is the blood test. If it comes back negative, then maybe they weren’t exposed to food poisoning, but if it is positive, I will know exactly that they have IBS and why (previous food poisoning). Once I establish a diagnosis, I often still go on to prescribe rifaximin as a first-line therapy because of its safety and efficacy. If they respond, then we know the IBS must have been caused by some underlying SIBO or some other dysbiosis. If there is still no response, I may move toward a low-FODMAP (LFD) diet or even a low-fermentation diet. That is a bit more liberal than the LFD and easier on patients. If a patient is truly refractory to all of that, I may try something like ondansetron, which has a lot of good data showing that it is effective at slowing transit down. Of course, we also have Viberzi (eluxadoline, Allergan) as another option to slow the gut down.

In IBS-C, I still believe the microbiome is important and offers us a decent chance to relieve symptoms. If a patient has methane on a breath test, I will treat that methane. If that does not improve constipation, I move on to the prokinetics, which have been incredibly important. With drugs like Amitiza (lubiprostone, Takeda), Trulance (plecanatide, Synergy) and Linzess (linaclotide, Allergan), I think it is best to strategize. How severe is the constipation? In cases where it is more on the mild side, I tend to go with lubiprostone. On the other end of the spectrum is linaclotide, which is much more potent for creating diarrhea, so we reserve that for more severe constipation.

We have a lot of options for IBS, and I truly think medical management of this disease has been improving with time. It will be exciting to see what comes next and how these new discoveries will help us serve our patients.

Disclosures: Pimentel reports financial ties to Commonwealth Laboratories, Gemelli Biotech, Naia Pharmaceuticals. Salix, Shire and Synthetic Biologics.

In my clinic, it still feels like we get countless referrals for irritable bowel syndrome.

We have gained so much knowledge and obtained so many new treatments in our arsenal over the years, but we are still going to need more solutions going forward if we are going to successfully serve all our patients. We need to build on this knowledge and keep making strides to ensure our patients are getting adequate care.

In the medical management of IBS, there appears to be an increasing level of understanding that the disease, particularly diarrhea-predominant IBS and mixed IBS, is a microbiome disease. That has probably been the most fruitful area of research and continues to be very exciting. Numerous abstracts and studies published over the last year that small intestinal bacterial overgrowth, for example, is a common underlying cause of IBS. New deep sequencing studies have revealed the exact organisms that might be responsible for the bloating in IBS. Other studies seem to show just how overabundant E. coli and Klebsiella are among patients with SIBO and IBS. The knowledge of those bugs and how they impact gut function and symptoms in our patients offers us new targets to explore for drug development.

Mark Pimentel, MD
Mark Pimentel

However, I think we need to be careful where we take this new information on the role of the microbiome in IBS. Specifically, I think the optimism about fecal microbiota transplant needs to go away. We now have at least five randomized controlled trials that have explored the topic, and none of the data are particularly promising. FMT has been under increasing scrutiny since a death was reported this summer. That alone should give us pause. I just hope people do not keep gravitating toward FMT for IBS.

Diagnosis

I still believe that one of the more exciting developments has been the ability to diagnose IBS. From a patient perspective, it can be easy to feel dismissed. They are told constantly that their symptoms are psychological, that it is in their heads. If they walk away from a doctor’s office without knowing what is wrong, without a diagnosis, they are not going to feel very confident in their chances of managing their disease.

We’ve been working to develop a blood test (IBS Smart, Gemelli Biotech) that has shown incredible potential. It was developed from our findings that Cytolethal distending toxin B and anti-vinculin levels are elevated in patients with IBS-D and IBS-M. We just finished a study on a second generation of the test that showed it had a specificity over 90% for either marker, and a positive predictive value of 98%. Doctors are going to use this in their practice and know, for sure, if a patient has IBS. It has the chance to be an incredibly useful tool, particularly in primary care. IBS can be a little scary in primary care because diarrhea can be caused by a lot of things. It could be celiac disease or Crohn’s disease, and it leads to a lot of unnecessary colonoscopies. This test will get us to a diagnosis faster.

In the Pipeline

Over the years, we have seen more and more pharmacological agents become available. Recently we have had two pretty exciting new additions to treat IBS-C that come from the world of prokinetics. First, is Zelnorm (tegaserod, Sloan Pharma), which is something of an old friend. It was taken off the market in 2007, but now it is back. It has been reintroduced since the FDA approved it for women younger than 65 years with IBS-C.

Even more exciting is Motegrity (prucalopride, Takeda), which is another prokinetic agent, but one that is much more potent than tegaserod. It has been shown to be highly effective for constipation. Right now, it is only approved for chronic idiopathic constipation, but I think patients with IBS-C could benefit from it.

With all of the medical therapies available for IBS-D, it is starting to feel like we are making a dent. It is still a very serious and wide-spread condition, but anecdotally, patients seem to be improving, and we are seeing less and less IBS-D in our practice. IBS-C is a different story. Constipation has been a much tougher nut to crack. Despite the numerous drugs available, we still need better therapy. We have been focusing our work on targeting methane and attempting to inhibit it. If we can find a way to get rid of that methane, maybe we can improve that subset of patients with constipation in much the same way that we help patients with IBS-D by using Xifaxan (rifaximin, Salix). However, it is likely that these therapies will take a little bit of time before they become available. If I had to guess, I would say that they will not be coming down the pipeline for another 2 to 3 years.

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In the Clinic

If I see a patient who might have IBS-D or IBS-M, the first thing I’m reaching for is the blood test. If it comes back negative, then maybe they weren’t exposed to food poisoning, but if it is positive, I will know exactly that they have IBS and why (previous food poisoning). Once I establish a diagnosis, I often still go on to prescribe rifaximin as a first-line therapy because of its safety and efficacy. If they respond, then we know the IBS must have been caused by some underlying SIBO or some other dysbiosis. If there is still no response, I may move toward a low-FODMAP (LFD) diet or even a low-fermentation diet. That is a bit more liberal than the LFD and easier on patients. If a patient is truly refractory to all of that, I may try something like ondansetron, which has a lot of good data showing that it is effective at slowing transit down. Of course, we also have Viberzi (eluxadoline, Allergan) as another option to slow the gut down.

In IBS-C, I still believe the microbiome is important and offers us a decent chance to relieve symptoms. If a patient has methane on a breath test, I will treat that methane. If that does not improve constipation, I move on to the prokinetics, which have been incredibly important. With drugs like Amitiza (lubiprostone, Takeda), Trulance (plecanatide, Synergy) and Linzess (linaclotide, Allergan), I think it is best to strategize. How severe is the constipation? In cases where it is more on the mild side, I tend to go with lubiprostone. On the other end of the spectrum is linaclotide, which is much more potent for creating diarrhea, so we reserve that for more severe constipation.

We have a lot of options for IBS, and I truly think medical management of this disease has been improving with time. It will be exciting to see what comes next and how these new discoveries will help us serve our patients.

Disclosures: Pimentel reports financial ties to Commonwealth Laboratories, Gemelli Biotech, Naia Pharmaceuticals. Salix, Shire and Synthetic Biologics.