Feature

Guest commentary: It’s time to deepen our understanding of abdominal pain in IBS

Eric Shah
Eric Shah

In this guest commentary, Eric D. Shah, MD, MBA, director of the Gastrointestinal Motility Center at Dartmouth-Hitchcock Medical Center, discusses his recent study on abdominal pain in irritable bowel syndrome and argues that stratifying patients could evolve past bowel habits alone.

Irritable bowel syndrome is defined by two cardinal symptoms: altered bowel habits and abdominal pain. We understand the first, altered bowel habits, pretty well. The Rome IV framework that we use to break down this complex disease and categorize treatments is, at its core, geared toward either reducing the number of bowel movements in patients with diarrhea-predominant IBS (IBS-D) or increasing them in patients with constipation-predominant IBS (IBS-C). However, we have a problem regarding the second symptom, abdominal pain.

In our most recent iteration of the Rome criteria, pain is defined similarly in both IBS-D and IBS-C. In practice, we know that our patients experience abdominal pain quite differently, but we currently do not have a way to conceptualize this in an organized manner. In our recent study published in the American Journal of Gastroenterology, we set out to understand how abdominal pain is experienced among the current IBS subtypes and to explore whether patients with IBS-D, IBS-C, or mixed-bowel pattern IBS (IBS-M) experience pain differently. We identified 1,158 actively symptomatic individuals with abdominal pain related to IBS from an age, sex, and geographically adjusted cohort of 70,000 adults across the U.S. in the recent National GI Survey. Interestingly, most actively symptomatic individuals had IBS-M (almost 60%), while roughly 20% each had IBS-D or IBS-C. We used a validated instrument (GI-PROMIS) to understand how bothersome, frequent, and severe their abdominal pain was over the past week, and to localize the regions of the abdomen affected by pain.

Infographic on abdominal pain in IBS
In this guest commentary, Eric D. Shah, MD, MBA, director of the Gastrointestinal Motility Center at Dartmouth-Hitchcock Medical Center, discusses his recent study on abdominal pain in irritable bowel syndrome and argues that stratifying patients could evolve past bowel habits alone.

Most importantly, we found that individuals with IBS experience pain quite differently based on their subtype defined by bowel habits. Patients with IBS-C experience more bothersome and frequent abdominal pain, and that abdominal pain interferes with daily activities more in IBS-C as compared to IBS-D or IBS-M. Bothersomeness and frequency of abdominal pain in IBS-D and IBS-M was quite similar. Pain was more diffuse and generalized throughout the abdomen in IBS-C and IBS-M, while pain was localized more in the lower regions with IBS-D.

Putting these findings into context, it actually seems that our existing framework based on bowel symptoms actually captures meaningful differences in abdominal pain as well. Are the five on-label IBS-C drugs and three on-label IBS-D drugs really interchangeable, or can we select patients for therapy based on their symptom experience? Is abdominal pain an even more important consideration in IBS-C than we realize? As we now recognize several mechanisms of IBS that can be effectively targeted, including altered gut microbiota, bile acid diarrhea, and brain-gut interactions, we can use these findings as a start toward refining the IBS subtypes to better capture not only the spectrum of bowel symptoms, but also the spectrum of abdominal symptoms which our patients experience.

Our findings also suggest that IBS-M was the most common actively symptomatic subtype of IBS. This contrasts to the relatively low prevalence of IBS-M compared to IBS-C or IBS-D in prior studies. One possible explanation for this finding is that we simply lack therapies for IBS-M and that this results in suboptimal treatment, or even a good understanding of whether IBS-M represents overflow diarrhea with IBS-C or a distinct entity unto itself. Another explanation is that abdominal pain may be the most bothersome complaint in some IBS individuals compared with bowel habits, and that subtyping these pain-predominant patients by bowel habit may not be the best approach to treatment rather than targeting the pain itself. Recent efforts to understand the effects of Xifaxan (rifaximin, Salix) in constipated IBS individuals, and to develop colonic formulations of Linzess (linaclotide, Ironwood), may find relief for this population — but only if we can find ways to classify this population of patients to ensure that investigational treatments mainly targeting abdominal — or sensory — symptoms of IBS can be appropriately evaluated in clinical trials.

Several limitations and unanswered questions are important to consider from our study. First, treatment effects may alter the reported pain experience of IBS-D and IBS-C patients that complicate any one-time snapshot in a cross-sectional survey design. It is possible that this effect could be mitigated by the unfortunate reality that IBS patients underutilize their pain treatments, with as few as 30% using their prescribed treatments for pain episodes in one study. There may also be differences in comorbid disorders, catastrophizing behaviors, and coping skills by IBS subtype, which we know impact the pain experience but are underrecognized. Alternatively, there may be pathophysiologic differences that drive IBS-D compared with IBS-C that explain differences in abdominal pain.

Ultimately, it is important to consider the abdominal (or sensory) group of symptoms in IBS patients, rather than focusing solely on swinging across the bowel symptom pendulum. We should first recognize that our FDA composite responder endpoints for IBS-D and IBS-C do a great job at requiring meaningful improvements in abdominal pain, and that our existing treatments do quite well in improving pain for our patients. Given the unprecedented number of treatments we now have for this disease, we can start to explore how the match these treatments to our patients to fully address the global symptom spectrum that comprises IBS.

Reference:

Hellström PM, et al. Am J Gastroenterol. 2011;doi: 10.1038/ajg.2011.78.

Shah ED, et al. Am J Gastroenterol. 2020;doi:10.14309/ajg.0000000000000502.

Disclosure: Shah reports no relevant financial disclosures.

 

Eric Shah
Eric Shah

In this guest commentary, Eric D. Shah, MD, MBA, director of the Gastrointestinal Motility Center at Dartmouth-Hitchcock Medical Center, discusses his recent study on abdominal pain in irritable bowel syndrome and argues that stratifying patients could evolve past bowel habits alone.

Irritable bowel syndrome is defined by two cardinal symptoms: altered bowel habits and abdominal pain. We understand the first, altered bowel habits, pretty well. The Rome IV framework that we use to break down this complex disease and categorize treatments is, at its core, geared toward either reducing the number of bowel movements in patients with diarrhea-predominant IBS (IBS-D) or increasing them in patients with constipation-predominant IBS (IBS-C). However, we have a problem regarding the second symptom, abdominal pain.

In our most recent iteration of the Rome criteria, pain is defined similarly in both IBS-D and IBS-C. In practice, we know that our patients experience abdominal pain quite differently, but we currently do not have a way to conceptualize this in an organized manner. In our recent study published in the American Journal of Gastroenterology, we set out to understand how abdominal pain is experienced among the current IBS subtypes and to explore whether patients with IBS-D, IBS-C, or mixed-bowel pattern IBS (IBS-M) experience pain differently. We identified 1,158 actively symptomatic individuals with abdominal pain related to IBS from an age, sex, and geographically adjusted cohort of 70,000 adults across the U.S. in the recent National GI Survey. Interestingly, most actively symptomatic individuals had IBS-M (almost 60%), while roughly 20% each had IBS-D or IBS-C. We used a validated instrument (GI-PROMIS) to understand how bothersome, frequent, and severe their abdominal pain was over the past week, and to localize the regions of the abdomen affected by pain.

Infographic on abdominal pain in IBS
In this guest commentary, Eric D. Shah, MD, MBA, director of the Gastrointestinal Motility Center at Dartmouth-Hitchcock Medical Center, discusses his recent study on abdominal pain in irritable bowel syndrome and argues that stratifying patients could evolve past bowel habits alone.

Most importantly, we found that individuals with IBS experience pain quite differently based on their subtype defined by bowel habits. Patients with IBS-C experience more bothersome and frequent abdominal pain, and that abdominal pain interferes with daily activities more in IBS-C as compared to IBS-D or IBS-M. Bothersomeness and frequency of abdominal pain in IBS-D and IBS-M was quite similar. Pain was more diffuse and generalized throughout the abdomen in IBS-C and IBS-M, while pain was localized more in the lower regions with IBS-D.

Putting these findings into context, it actually seems that our existing framework based on bowel symptoms actually captures meaningful differences in abdominal pain as well. Are the five on-label IBS-C drugs and three on-label IBS-D drugs really interchangeable, or can we select patients for therapy based on their symptom experience? Is abdominal pain an even more important consideration in IBS-C than we realize? As we now recognize several mechanisms of IBS that can be effectively targeted, including altered gut microbiota, bile acid diarrhea, and brain-gut interactions, we can use these findings as a start toward refining the IBS subtypes to better capture not only the spectrum of bowel symptoms, but also the spectrum of abdominal symptoms which our patients experience.

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Our findings also suggest that IBS-M was the most common actively symptomatic subtype of IBS. This contrasts to the relatively low prevalence of IBS-M compared to IBS-C or IBS-D in prior studies. One possible explanation for this finding is that we simply lack therapies for IBS-M and that this results in suboptimal treatment, or even a good understanding of whether IBS-M represents overflow diarrhea with IBS-C or a distinct entity unto itself. Another explanation is that abdominal pain may be the most bothersome complaint in some IBS individuals compared with bowel habits, and that subtyping these pain-predominant patients by bowel habit may not be the best approach to treatment rather than targeting the pain itself. Recent efforts to understand the effects of Xifaxan (rifaximin, Salix) in constipated IBS individuals, and to develop colonic formulations of Linzess (linaclotide, Ironwood), may find relief for this population — but only if we can find ways to classify this population of patients to ensure that investigational treatments mainly targeting abdominal — or sensory — symptoms of IBS can be appropriately evaluated in clinical trials.

Several limitations and unanswered questions are important to consider from our study. First, treatment effects may alter the reported pain experience of IBS-D and IBS-C patients that complicate any one-time snapshot in a cross-sectional survey design. It is possible that this effect could be mitigated by the unfortunate reality that IBS patients underutilize their pain treatments, with as few as 30% using their prescribed treatments for pain episodes in one study. There may also be differences in comorbid disorders, catastrophizing behaviors, and coping skills by IBS subtype, which we know impact the pain experience but are underrecognized. Alternatively, there may be pathophysiologic differences that drive IBS-D compared with IBS-C that explain differences in abdominal pain.

Ultimately, it is important to consider the abdominal (or sensory) group of symptoms in IBS patients, rather than focusing solely on swinging across the bowel symptom pendulum. We should first recognize that our FDA composite responder endpoints for IBS-D and IBS-C do a great job at requiring meaningful improvements in abdominal pain, and that our existing treatments do quite well in improving pain for our patients. Given the unprecedented number of treatments we now have for this disease, we can start to explore how the match these treatments to our patients to fully address the global symptom spectrum that comprises IBS.

Reference:

Hellström PM, et al. Am J Gastroenterol. 2011;doi: 10.1038/ajg.2011.78.

Shah ED, et al. Am J Gastroenterol. 2020;doi:10.14309/ajg.0000000000000502.

Disclosure: Shah reports no relevant financial disclosures.