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IBS: Understanding a Common Yet Misunderstood Condition
Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.
Unfortunately, , according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.
Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.
A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.
“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.
IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.
Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
Diagnostic Pathway
One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”
IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).
Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.
Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.
Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.
If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
New Understanding of IBS Etiology
Now, advances in the understanding of IBS are changing the approach to the disease.
“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”
Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.
Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.
The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.
CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.
This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”
Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.
“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.
Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.
“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”
The blood test also can identify IBS-M but not IBS-C.
Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
Diet as a Treatment Option
Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”
A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).
Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”
A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
Pharmacotherapy for IBS
Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.
Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.
Antidiarrheal agents include loperamide and diphenoxylate.
For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.
Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
Targeting the Gut-Brain Relationship
Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.
“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”
Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.
“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.
Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.
Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.
Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.
Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”
Finally, all the experts agree that more research is needed.
“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”
Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.
Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.
Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.
Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.
A version of this article appeared on Medscape.com.
Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.
Unfortunately, , according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.
Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.
A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.
“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.
IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.
Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
Diagnostic Pathway
One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”
IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).
Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.
Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.
Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.
If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
New Understanding of IBS Etiology
Now, advances in the understanding of IBS are changing the approach to the disease.
“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”
Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.
Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.
The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.
CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.
This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”
Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.
“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.
Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.
“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”
The blood test also can identify IBS-M but not IBS-C.
Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
Diet as a Treatment Option
Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”
A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).
Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”
A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
Pharmacotherapy for IBS
Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.
Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.
Antidiarrheal agents include loperamide and diphenoxylate.
For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.
Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
Targeting the Gut-Brain Relationship
Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.
“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”
Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.
“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.
Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.
Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.
Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.
Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”
Finally, all the experts agree that more research is needed.
“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”
Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.
Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.
Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.
Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.
A version of this article appeared on Medscape.com.
Irritable bowel syndrome (IBS) is one of the most common conditions encountered by both primary care providers and gastroenterologists, with a pooled global prevalence of 11.2%. This functional bowel disorder is characterized by abdominal pain or discomfort, diarrhea and/or constipation, and bloating.
Unfortunately, , according to Alan Desmond, MB, consultant in gastroenterology and general internal medicine, Torbay Hospital, UK National Health Service.
Desmond regularly sees patients who either haven’t been accurately diagnosed or have been told, “Don’t worry, it’s ‘just’ irritable bowel syndrome,” he said at the recent International Conference on Nutrition in Medicine.
A 2017 study involving nearly 2000 patients with a history of gastrointestinal (GI) symptoms found that 43.1% of those who met the criteria for IBS were undiagnosed, and among those who were diagnosed, 26% were not receiving treatment.
“Many clinicians vastly underestimate the impact functional GI symptoms have on our patients in lack of productivity, becoming homebound or losing employment, the inability to enjoy a meal with friends or family, and always needing to know where the nearest bathroom is, for example,” Desmond said in an interview.
IBS can profoundly affect patients’ mental health. One study found that 38% of patients with IBS attending a tertiary care clinic contemplated suicide because they felt hopeless about ever achieving symptom relief.
Today, several dietary, pharmacologic, and psychological/behavioral approaches are available to treat patients with IBS, noted William D. Chey, MD, AGAF, chief of the Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
“Each individual patient may need a different combination of these foundational treatments,” he said. “One size doesn’t fit all.”
Diagnostic Pathway
One reason IBS is so hard to diagnose is that it’s a “symptom-based disorder, with identification of the condition predicated upon certain key characteristics that are heterogeneous,” Chey said in an interview. “IBS in patient ‘A’ may not present the same way as IBS in patient ‘B,’ although there are certain foundational common characteristics.”
IBS involves “abnormalities in the motility and contractility of the GI tract,” he said. It can present with diarrhea (IBS-D), constipation (IBS-C), or a mixture or alternation of diarrhea and constipation (IBS-M).
Patients with IBS-D often have an exaggerated gastro-colonic response, while those with IBS-C often have a blunted response.
Beyond stool abnormalities and abdominal pain/discomfort, patients often report bloating/distension, low backache, lethargy, nausea, thigh pain, and urinary and gynecologic symptoms.
Historically, IBS has been regarded as a “diagnosis of exclusion” because classic diagnostic tests typically yield no concrete findings. Desmond noted that several blood tests, procedures, imaging studies, and other tests are available to rule out other organic GI conditions, as outlined in the Table.
If the patient comes from a geographical region where giardia is endemic, clinicians also should consider testing for the parasite, Chey said.
New Understanding of IBS Etiology
Now, advances in the understanding of IBS are changing the approach to the disease.
“The field is moving away from seeing IBS as a ‘wastebasket diagnosis,’ recognizing that there are other causes of a patient’s symptoms,” Mark Pimentel, MD, associate professor of medicine and gastroenterology, Cedars-Sinai, Los Angeles, said in an interview. “What’s made IBS so difficult to diagnose has been the absence of biological markers and hallmark findings on endoscopy.”
Recent research points to novel bacterial causes as culprits in the development of IBS. In particular, altered small bowel microbiota can be triggered by acute gastroenteritis.
Food poisoning can trigger the onset of IBS — a phenomenon called “postinfectious IBS (PI-IBS),” said Pimentel, who is also executive director of the Medically Associated Science and Technology Program at Cedars-Sinai. PI-IBS almost always takes the form of IBS-D, with up to 60% of patients with IBS-D suffering the long-term sequelae of food poisoning.
The types of bacteria most commonly associated with gastroenteritis are Shigella, Campylobacter, Salmonella, and Escherichia coli, Pimentel said. All of them release cytolethal distending toxin B (CdtB), causing the body to produce antibodies to the toxin.
CdtB resembles vinculin, a naturally occurring protein critical for healthy gut function. “Because of this molecular resemblance, the immune system often mistakes one for the other, producing anti-vinculin,” Pimentel explained.
This autoimmune response leads to disruptions in the gut microbiome, ultimately resulting in PI-IBS. The chain of events “doesn’t necessarily happen immediately,” Pimentel said. “You might have developed food poisoning at a party weeks or months ago.”
Acute gastroenteritis is common, affecting as many as 179 million people in the United States annually. A meta-analysis of 47 studies, incorporating 28,270 patients, found that those who had experienced acute gastroenteritis had a fourfold higher risk of developing IBS compared with nonexposed controls.
“The problem isn’t only the IBS itself, but the fact that people with PI-IBS are four times as likely to contract food poisoning again, which can further exacerbate IBS symptoms,” Pimentel said.
Diarrhea-predominant IBS can be detected through the presence of two blood biomarkers — anti-CdtB and anti-vinculin — in a blood test developed by Pimentel and his group.
“Elevation in either of these biomarkers establishes the diagnosis,” Pimentel said. “This is a breakthrough because it represents the first test that can make IBS a ‘diagnosis of inclusion.’”
The blood test also can identify IBS-M but not IBS-C.
Pimentel said that IBS-C is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. “Methane gas slows intestinal contractility, which might result in constipation,” he said.
Diet as a Treatment Option
Diet is usually the starting point for IBS treatment, Chey said. “The standard dietary recommendations, as defined by the National Institute for Health and Care Excellence Guidance for managing IBS, are reasonable and common sense — eating three meals a day, avoiding carbonated beverages, excess alcohol, and excess caffeine, and avoiding hard-to-digest foods that can be gas producing.”
A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs), which are carbohydrates that aren’t completely absorbed in the intestines, has been shown to be effective in alleviating GI distress in as many as 86% of patients with IBS, leading to improvements in overall GI symptoms as well as individual symptoms (eg, abdominal pain, bloating, constipation, diarrhea, and flatulence).
Desmond recommends the low FODMAP program delineated by Monash University in Australia. The diet should be undertaken only under the supervision of a dietitian, he warned. Moreover, following it on a long-term basis can have an adverse impact on dietary quality and the gut microbiome. Therefore, “it’s important to embark on stepwise reintroduction of FODMAPS under supervision to find acceptable thresholds that don’t cause a return of symptoms.”
A growing body of research suggests that following the Mediterranean diet can be helpful in reducing IBS symptoms. Chey said that some patients who tend to over-restrict their eating might benefit from a less restrictive diet than the typical low FODMAPs diet. For them, the Mediterranean diet may be a good option.
Pharmacotherapy for IBS
Nutritional approaches aren’t for everyone, Chey noted. “Some people don’t want to be on a highly restricted diet.” For them, medications addressing symptoms might be a better option.
Antispasmodics — either anticholinergics (hyoscine and dicyclomine) or smooth muscle relaxants (alverine, mebeverine, and peppermint oil) — can be helpful, although they can worsen constipation in a dose-dependent manner. It is advisable to use them on an as-needed rather than long-term basis.
Antidiarrheal agents include loperamide and diphenoxylate.
For constipation, laxatives (eg, senna, bisacodyl, polyethylene glycol, and sodium picosulfate) can be helpful.
Desmond noted that the American Gastroenterological Association does not recommend routine use of probiotics for most GI disorders, including IBS. Exceptions include prevention of Clostridioides difficile, ulcerative colitis, and pouchitis.
Targeting the Gut-Brain Relationship
Stress plays a role in exacerbating symptoms in patients with IBS and is an important target for intervention.
“If patients are living with a level of stress that’s impairing, we won’t be able to solve their gut issues until we resolve their stress issues,” Desmond said. “We need to calm the gut-microbiome-brain axis, which is multidimensional and bidirectional.”
Many people — even those without IBS — experience queasiness or diarrhea prior to a major event they’re nervous about, Chey noted. These events activate the brain, which activates the nervous system, which interacts with the GI tract. Indeed, IBS is now recognized as a disorder of gut-brain interaction, he said.
“We now know that the microbiome in the GI tract influences cognition and emotional function, depression, and anxiety. One might say that the gut is the ‘center of the universe’ to human beings,” Chey said.
Evidence-based psychological approaches for stress reduction in patients with IBS include cognitive behavioral therapy, specifically tailored to helping the patient identify associations between IBS symptoms and thoughts, emotions, and actions, as well as learning new behaviors and engaging in stress management. Psychodynamic (interpersonal) therapy enables patients to understand the connection between GI symptoms and interpersonal conflicts, emotional factors, or relationship difficulties.
Gut-directed hypnotherapy (GDH) is a “proven modality for IBS,” Desmond said. Unlike other forms of hypnotherapy, GDH focuses specifically on controlling and normalizing GI function. Studies have shown a reduction of ≥ 30% in abdominal pain in two thirds of participants, with overall response rates up to 85%. It can be delivered in an individual or group setting or via a smartphone.
Desmond recommends mindfulness-based therapy (MBT) for IBS. MBT focuses on the “cultivation of mindfulness, defined as intentional, nonjudgmental, present-focused awareness.” It has been found effective in reducing flares and the markers of gut inflammation in ulcerative colitis, as well as reducing symptoms of IBS.
Chey noted that an emerging body of literature supports the potential role of acupuncture in treating IBS, and his clinic employs it. “I would like to see further research into other areas of CAM [complementary and alternative medicine], including herbal approaches to IBS symptoms as well as stress.”
Finally, all the experts agree that more research is needed.
“The real tragedy is that the NIH invests next to nothing in IBS, in contrast to inflammatory bowel disease and many other conditions,” Pimentel said. “Yet IBS is 45 times more common than inflammatory bowel disease.”
Pimentel hopes that with enough advocacy and recognition that IBS isn’t “just stress-related,” more resources will be devoted to understanding this debilitating condition.
Desmond is the author of a book on the benefits of a plant-based diet. He has also received honoraria, speaking, and consultancy fees from the European Space Agency, Dyson Institute of Engineering and Technology, Riverford Organic Farmers, Ltd., Salesforce Inc., Sentara Healthcare, Saudi Sports for All Federation, the Physicians Committee for Responsible Medicine, The Plantrician Project, Doctors for Nutrition, and The Happy Pear.
Pimentel is a consultant for Bausch Health, Ferring Pharmaceuticals, and Ardelyx. He holds equity in and is also a consultant for Dieta Health, Salvo Health, Cylinder Health, and Gemelli Biotech. Cedars-Sinai has a licensing agreement with Gemelli Biotech and Hobbs Medical.
Chey is a consultant to AbbVie, Ardelyx, Atmo, Biomerica, Gemelli Biotech, Ironwood Pharmaceuticals, Nestlé, QOL Medical, Phathom Pharmaceuticals, Redhill, Salix/Valeant, Takeda, and Vibrant. He receives grant/research funding from Commonwealth Diagnostics International, Inc., US Food and Drug Administration, National Institutes of Health, QOL Medical, and Salix/Valeant. He holds stock options in Coprata, Dieta Health, Evinature, FoodMarble, Kiwi Biosciences, and ModifyHealth. He is a board or advisory panel member of the American College of Gastroenterology, GI Health Foundation, International Foundation for Gastrointestinal Disorders, Rome. He holds patents on My Nutrition Health, Digital Manometry, and Rectal Expulsion Device.
A version of this article appeared on Medscape.com.
Breath Gas Patterns Predict Response to Low FODMAP Diet
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
FROM ACG 2024
Ultraprocessed Foods Associated With Relapse Risk in Crohn’s Disease
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM UEG 2024
Live Rotavirus Vaccine Safe for Newborns of Biologic-Treated Moms With IBD
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
No adverse events or impairment of the immune system emerged in babies at 7 days, 1 month, and 9 months post vaccination, in findings from a small Canadian study published in Clinical Gastroenterology and Hepatology.
The study found normal extended immune function testing in infants despite third-trimester maternal biologic therapy and regardless of circulating drug levels. The data provide reassurance about live rotavirus vaccination in this population and may also offer insights into the safety of other live vaccines in biologic-exposed individuals, wrote investigators led by gastroenterologist Cynthia H. Seow, MD, a professor in the Cumming School of Medicine at the University of Calgary in Alberta, Canada.
“Despite the well-established safety and effectiveness of non–live vaccination in individuals with IBD, including those on immunomodulators and biologic therapy, vaccine uptake in pregnant women with IBD and their infants remains suboptimal,” Seow said in an interview. This largely arises from maternal and physician concerns regarding transplacental transfer of IBD therapies and their impact on the safety of vaccination.
“These concerns were heightened after reports emerged of five fatal outcomes following the administration of the live Bacille Calmette-Guérin [BCG] vaccine in biologic-exposed infants. However, it had already been reported that inadvertent administration of the live oral rotavirus vaccine, a very different vaccine in terms of target and mechanism of action, in biologic-exposed individuals had not been associated with significant adverse effects,” she said.
They undertook their analysis with the hypothesis that vaccination would carry low risk, although the live oral vaccine is not currently recommended in biologic-exposed infants. “Yet rotavirus is a leading cause of severe, dehydrating diarrhea in children under the age of 5 years globally, and vaccination has led to significant reductions in hospitalizations and mortality,” Seow added.
Provision of the vaccine to anti–tumor necrosis factor (TNF)–exposed infants has been incorporated into the Canadian Public Health and Immunization guidelines, as the majority of the biologic-exposed infants were exposed to anti-TNF agents. “And with collection of further data, we expect that this will be extended to other biologic agent exposure. These data are important to pregnant women with IBD as they help to normalize their care. Pregnancy is difficult enough without having to remember exceptions to care,” Seow said.
“Before some of the studies came out, broad guidelines recommended that live vaccines should not be used in biologic-exposed infants, but this had been thought to be overly zealous and too conservative, and the risk was thought to be low,” said Elizabeth Spencer, MD, an assistant professor of pediatrics in the Division of Pediatric Gastroenterology at the Icahn School of Medicine at Mount Sinai in New York City, in an interview. Spencer was not involved in the Canadian study.
“At our center, we had some moms on biologics during pregnancy who forgot and had their babies vaccinated for rotavirus, and the babies were all fine,” she said.
The safety of this vaccine has been confirmed by several small studies and recently the PIANO Helmsley Global Consensus on Pregnancy and Inflammatory Bowel Disease, which was presented at Digestive Disease Week 2024. The consensus encompasses preconception counseling and the safety of IBD medications during pregnancy and lactation.
“Another concern, however, was that giving a live GI bug like rotavirus to babies might overstimulate their immune systems and provoke IBD,” Spencer added. “While a number of population-based studies in the US and Europe showed that was not the case, at least in the general population, there was a suggestion that, down the road, vaccination might be mildly protective against IBD in some cases.”
She added the caveat that these studies were not done in mothers and their babies with IBD, who might be inherently at greater risk for IBD. “So, a question for future research would be, ‘Is immune stimulation of the gut in IBD moms and their babies a good or a bad thing for their gut?’ ”
Spencer conceded that “the data present a bit of a blurry picture, but I think it’s always better just to vaccinate according to the regular schedule. The current data say there is no added risk, but it would be nice to look specifically at risk in moms with IBD and their children.”
The Study
The prospective cohort study is a substudy of a larger 2023 one that included biologic use in a range of maternal illnesses, not just IBD.
For the current study, Seow and colleagues identified 57 infants born to 52 mothers with IBD attending a pregnancy clinic at the University of Calgary in the period 2019-2023. Almost 81% of the mothers had Crohn’s disease, and the median duration of IBD was 10 years. The median gestational age at delivery was 39 weeks, and almost 60% of deliveries were vaginal. The infants had been exposed in utero to infliximab (n = 21), adalimumab (n = 19), vedolizumab (n = 10), and ustekinumab (n = 7) in the third trimester.
The 57 biologic-exposed infants underwent standardized clinical assessments, drug concentration, and immune function testing. The live oral rotavirus vaccine series was provided to 50 infants, with the first dose at a median of 13 weeks of age. Immunologic assessments validated for age were normal in all infants despite median infliximab concentrations of 6.1 μg/mL (range, 0.4-28.8 μg/mL), adalimumab concentrations of 1.7 μg/mL (range, 0.7-7.9 μg/mL), ustekinumab concentrations of 0.6 μg/mL (range, 0-1.1), and undetectable for vedolizumab at 10.7 weeks of age.
As anticipated, infant immune function was normal regardless of circulating drug levels.
The overall message, said Seow, is “healthy mum equals healthy baby. Be more concerned regarding active inflammation than active medications. In almost all circumstances, treat to target in pregnancy as you would in the nonpregnant state.” She added, however, that further studies are needed to determine the safety and optimal timing of other live vaccines, such as the BCG, in the presence of biologic therapy.
This study was funded by the Alberta Children’s Hospital Research Institute. Seow reported advisory/speaker’s fees for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi, Bristol-Myers Squibb, Pharmascience, and Lilly, as well as funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, the Canadian Institutes of Health Research, and Calgary Health Trust, and data safety monitoring from New South Wales Government Health, Australia. Multiple coauthors disclosed similar consulting or speaker relationships with private industry. Spencer had no competing interests with regard to her comments.
A version of this article first appeared on Medscape.com.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
GI Docs Will Need to Forge a ‘Human-Computer Cooperative’
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Several artificial intelligence (AI) technologies are emerging that will change the management of gastrointestinal (GI) diseases sooner rather than later. One of the leading researchers working toward that AI-driven future is Ryan W. Stidham, MD, MS, AGAF, associate professor of gastroenterology and computational medicine and bioinformatics at the University of Michigan, Ann Arbor.
Stidham’s work focuses on leveraging AI to develop automated systems that better quantify disease activity and aid gastroenterologists in their decision-making. He also serves as a meber of AGA's AI Task Force. what the technology may do to improve physician efficiency, and why gastroenterologists shouldn’t be worried about being replaced by machines any time soon.
How did you first become involved in studying AI applications for GI conditions?
My medical training coincided with the emergence of electronic health records (EHRs) making enormous amounts of data, ranging from laboratory results to diagnostic codes and billing records, readily accessible.
I quickly contracted data analytics fever, but a major problem became apparent: EHRs and medical claims data alone only weakly describe a patient. Researchers in the field were excited to use machine learning for personalizing treatment decisions for GI conditions, including inflammatory bowel disease (IBD). But no matter how large the dataset, the EHRs lacked the most rudimentary descriptions: What was the patient’s IBD phenotype? Where exactly was the disease located?
I could see machine learning had the potential to learn and reproduce expert decision-making. Unfortunately, we were fueling this machine-learning rocket ship with crude data unlikely to take us very far. Gastroenterologists rely on data in progress notes, emails, interpretations of colonoscopies, and radiologists’ and pathologists’ reviews of imaging to make treatment decisions, but that information is not well organized in any dataset.
I wanted to use AI to retrieve that key information in text, images, and video that we use every day for IBD care, automatically interpreting the data like a seasoned gastroenterologist. Generating higher-quality data describing patients could take our AI models from interesting research to useful and reliable tools in clinical care.
How did your early research go about trying to solve that problem?
My GI career began amid the IBD field shifting from relying on symptoms alone to objective biomarkers for IBD assessment, particularly focusing on standardized scoring of endoscopic mucosal inflammation. However, these scores were challenged with interobserver variability, prompting the need for centralized reading. More importantly, these scores are qualitative and do not capture all the visual findings an experienced physician appreciates when assessing severity, phenotype, and therapeutic effect. As a result, even experts could disagree on the degree of endoscopic severity, and patients with obvious differences in the appearance of mucosa could have the same endoscopic score.
I asked myself: Are we really using these measures to make treatment decisions and determine the effectiveness of investigational therapies? I thought we could do better and aimed to improve endoscopic IBD assessments using then-emerging digital image analysis techniques.
Convolutional neural network (CNN) modeling was just becoming feasible as computing performance increased. CNNs are well suited for complex medical image interpretation, using an associated “label,” such as the presence or grade of disease, to decipher the complex set of image feature patterns characterizing an expert’s determination of disease severity.
How did you convert the promise of CNN into tangible results?
The plan was simple: Collect endoscopic images from patients with IBD, find some experts to grade IBD severity on the images, and train a CNN model using the images and expert labels.
In 2016, developing a CNN wasn’t easy. There was no database of endoscopic images or simple methods for image labeling. The CNN needed tens of thousands of images. How were we to collect enough images with a broad range of IBD severity? I also reached some technical limits and needed help solving computational challenges.
Designing our first IBD endoscopic CNN took years of reading, coursework, additional training, and a new host of collaborators.
Failure was frequent, and my colleagues and I spent a lot of nights and weekends looking at thousands of individual endoscopic images. But we eventually had a working model for grading endoscopic severity, and its performance exceeded our expectations.
To our surprise, the CNN model grading of ulcerative colitis severity almost perfectly matched the opinion of IBD experts. We introduced the proof of concept that AI could automate complex disease measurement for IBD.
What took us 3 years in 2016 would take about 3 weeks today.
You have said that AI could help reduce the substantial administrative burdens in medicine today. What might an AI-assisted future look like for time-strapped gastroenterologists?
We will be spending more time on complex decision-making and developing treatment plans, with less time needed to hunt for information in the chart and administrative tasks.
The practical applications of AI will chip away at tedious mechanical tasks, soon to be done by machines, reclaiming time for gastroenterologists.
For example, automated documentation is almost usable, and audio recordings in the clinic could be leveraged to generate office notes.
Computer vision analysis of endoscopic video is generating draft procedural notes and letters to patients in a shared language, as well as recommending surveillance intervals based on the findings.
Text processing is already being used to automate billing and manage health maintenance like vaccinations, laboratory screening, and therapeutic drug monitoring.
Unfortunately, I don’t think that AI will immediately help with burnout. These near-term AI administrative assistant advantages, however, will help us manage the increasing patient load, address physician shortages, and potentially improve access to care in underserved areas.
Were there any surprises in your work?
I must admit, I was certain AI would put us gastroenterologists to shame. Over time, I have reversed that view.
AI really struggles to understand the holistic patient context when interpreting disease and predicting what to do for an individual patient. Humans anticipate gaps in data and customize the weighting of information when making decisions for individuals. An experienced gastroenterologist can incorporate risks, harms, and costs in ways AI is several generations from achieving.
With certainty, AI will outperform gastroenterologists for tedious and repetitive tasks, and we should gladly expect AI to assume those responsibilities. However, many unknowns remain in the daily management of GI conditions. We will continue to rely on the clinical experience, creativity, and improvisation of gastroenterologists for years to come.
Has there been a turning-point moment when it felt like this technology moved from being more theoretical to something with real-world clinical applications?
Last spring, I saw a lecture by Peter Lee, who is president of Microsoft Research and a leader in developing AI-powered applications in medicine and scientific research, demonstrating how a large language model (LLM) could “understand” medical text and generate responses to questions. My jaw dropped.
We watched an LLM answer American Board of Internal Medicine questions with perfect explanations and rationale. He demonstrated how an audio recording of a clinic visit could be used to automatically generate a SOAP (subjective, objective assessment and plan) note. It was better than anything I would have drafted. He also showed how the LLM could directly ingest EHR data, without any modification, and provide a great diagnosis and treatment plan. Finally, LLM chatbots could carry on an interactive conversation with a patient that would be difficult to distinguish from a human physician.
The inevitability of AI-powered transformations in gastroenterology care became apparent.
Documentation, billing, and administrative work will be handled by AI. AI will collect and organize information for me. Chart reviews and even telephone/email checkups on patients will be a thing of the past. AI chatbots will be able to discuss an individual patient’s condition and test results. Our GI-AI assistants will proactively collect information from patients after hospitalization or react to a change in labs.
AI will soon be an amazing diagnostician and will know more than me. So do we need to polish our resumes for new careers? No, but we will need to adapt to changes, which I believe on the whole will be better for gastroenterologists and patients.
What does adaptation look like for gastroenterologists over the next handful of years?
Like any other tool, gastroenterologists will be figuring out how to use AI prediction models, chatbots, and imaging analytics. Value, ease of use, and information-gain will drive which AI tools are ultimately adopted.
Memory, information recall, calculations, and repetitive tasks where gastroenterologists occasionally error or find tiresome will become the job of machines. We will still be the magicians, now aided by machines, applying our human strengths of contextual awareness, judgment, and creativity to find customized solutions for more patients.
That, I think, is the future that we are reliably moving toward over the next decade — a human-computer cooperative throughout gastroenterology (including IBD) and, frankly, all of medicine.
A version of this article appeared on Medscape.com.
Celiac Screening in Kids Appears Cost-Effective
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
Celiac disease (CD) is common, affecting about 1% of the population, but it remains underdiagnosed because of its heterogeneous presentation and limited provider awareness. Most cases are detected only after patients develop gastrointestinal symptoms or laboratory abnormalities.
In this cost-effectiveness analysis, Suasnabar and colleagues demonstrate that screening children for celiac disease would be highly cost-effective relative to the current practice of clinical detection. They modeled point-of-care-testing using tissue transglutaminase IgA in all 3-year-old children in the Netherlands. While both mass screening and case-finding (via a standardized questionnaire) would increase healthcare costs relative to current care, both strategies would improve quality of life (QoL), reduce long-term complications (such as osteoporosis and non-Hodgkin lymphoma), and minimize productivity losses in individuals with CD. In sensitivity analyses accounting for uncertainty in QoL inputs and in the utility of diagnosing and treating asymptomatic CD, each screening strategy remained well below accepted willingness-to-pay thresholds.
John B. Doyle, MD, is a gastroenterology fellow in the Division of Digestive and Liver Diseases at Columbia University Medical Center, New York City. Benjamin Lebwohl, MD, MS, AGAF, is professor of medicine and epidemiology at Columbia University Medical Center and director of clinical research at The Celiac Disease Center at Columbia. They have no conflicts of interest to declare.
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
If these screening strategies are deemed feasible by clinicians and patients, then implementation in routine care is needed, lead author Jan Heijdra Suasnabar, MSc, of Leiden University Medical Centre in the Netherlands, and colleagues reported.
“Cohort studies have shown that CD likely develops early in life and can be easily diagnosed by detection of CD-specific antibodies against the enzyme tissue transglutaminase type 2 (IgA-TG2),” the investigators wrote in Gastroenterology.
Despite the ease of diagnosis, as few as one in five cases of CD are detected using current clinical strategies, meaning many cases are diagnosed years after symptom onset.
“Such high rates of missed/delayed diagnoses have been attributed to CD’s varied and nonspecific symptoms, lack of awareness, and the resource-intensive process necessary to establish the diagnosis,” Heijdra Suasnabar and colleagues wrote. “From an economic perspective, the burden of CD translates into substantial excess healthcare and societal costs.”
These practice gaps prompted the present study, which explored the long-term cost effectiveness of mass CD screening and active case finding among pediatric patients.
The investigators employed a model-based cost-effectiveness analysis with a hypothetical cohort representing all children with CD in the Netherlands. Iterations of this model evaluated long-term costs as these children moved through the healthcare system along various CD detection strategies.
The first strategy was based on the current Dutch approach, which is the same as that in the United States: Patients are only evaluated for CD if they present with symptoms that prompt suspicion of disease. Based on data from population-based studies, the model assumed that approximately one in three cases would be detected using this strategy.
The second strategy involved mass screening using IgA-TG2 point-of-care testing (sensitivity, 0.94; specificity, 0.944) via youth health care clinics, regardless of symptoms.
The third strategy, called “active case finding,” represented something of an intermediate approach, in which children with at least 1 CD-related symptom underwent point-of-care antibody testing.
For both mass screening and active case finding strategies, a positive antibody test was followed with confirmatory diagnostic testing.
Compared with current clinical approach, mass screening added 7.46 more quality-adjusted life-years (QALYs) per CD patient with an increased cost of €28,635 per CD patient. Active case finding gained 4.33 QALYs per CD patient while incurring an additional cost of €15,585 per CD patient.
Based on a willingness-to-pay threshold of €20,000 per QALY, the investigators deemed both strategies “highly cost effective,” compared with current standard of care. Some of these costs were offset by “substantial” reductions in productivity losses, they noted, including CD-related absences from work and school.
“Our results illustrate how an earlier detection of CD through screening or case finding, although more costly, leads to improved health outcomes and a reduction in disease burden, compared with current care,” Heijdra Suasnabar and colleagues wrote.
Their concluding remarks highlighted the conservative scenarios built into their model, and suggested that their findings offer solid evidence for implementing new CD-testing strategies.
“If found to be feasible and acceptable by clinicians and patients, these strategies should be implemented in the Netherlands,” they wrote.This study was supported by the Netherlands Organization for Health Research and Development. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
FDA Approves Ustekinumab Biosimilar Otulfi
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
A version of this article first appeared on Medscape.com.
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
A version of this article first appeared on Medscape.com.
This is the fourth ustekinumab biosimilar approved in the United States. Like the reference product, ustekinumab-aauz is indicated for:
- Patients 6 years or older with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
- Patients 6 years or older with active psoriatic arthritis
- Adult patients with moderately to severely active Crohn’s disease
- Adult patients with moderately to severely active ulcerative colitis
Ustekinumab-aauz, produced by a partnership between Fresenius Kabi and Formycon, has two formulations: subcutaneous injection (45 mg/0.5 mL or 90 mg/mL solution in a single-dose prefilled syringe) or intravenous infusion (130 mg/26 mL solution in a single-dose vial).
The biosimilar will launch in the United States “no later than February 22, 2025,” according to the press release, “in accordance with the patent settlement between Fresenius Kabi, Formycon, and Johnson & Johnson.”
Ustekinumab-aauz is Fresenius Kabi’s fourth biosimilar granted US approval, behind adalimumab-aacf (Idacio), tocilizumab-aazg (Tyenne), and pegfilgrastim-fpgk (Stimufend).
A version of this article first appeared on Medscape.com.
New Biologic Tulisokibart Beats Placebo in Ulcerative Colitis Trial
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
In one cohort of 135 patients, the primary endpoint of clinical remission occurred in 26% of those given the novel antibody to tumor necrosis factor–like cytokine 1A (TL1A) vs 1% given placebo (95% CI, 14-37, P < .001). In a smaller cohort of 43 patients genetically pretested for likely response to the new biologic, remission after treatment was only slightly higher at 32% vs 11% (95% CI, 2-38, P = .02).
The incidence of adverse events was similar in both arms, and most events were mild.
The 12-week induction trial, conducted in 14 countries by the ARTEMIS-UC Study Group and led by Bruce E. Sands, MD, MS, AGAF, a professor of medicine at Icahn School of Medicine at Mount Sinai and system chief in the Division of Gastroenterology at Mount Sinai Health System in New York City, was published in The New England Journal of Medicine.
“Our results suggest that important clinical benefit may be achieved through TL1A blockade in patients with UC,” Dr. Sands said in an interview, adding that this is the first rigorous study of a drug class with an entirely new mechanism of action that may be beneficial in other immune-mediated and fibrotic diseases.
“And it is also the first prospective randomized controlled trial in IBD to incorporate a precision-medicine approach using a predictive biomarker for response in a drug development program,” he added.
Dr. Sands stressed the urgent need for new therapies since, despite the approval of multiple new classes of agents, both small molecules and biologics, “there is still a plateau of efficacy in that less than 50% of patients achieve remission at a year.”
He added that UC may progress over time owing to fibrosis of the bowel, a condition not directly or safely addressed by any existing therapies. “Identifying novel targets such as TL1A may allow us to address a different subpopulation of patients who may not respond to the targets addressed by existing therapies,” he said.
In agreement is Jason K. Hou, MD, MS, AGAF, an associate professor of medicine at Baylor College of Medicine and section chief of gastroenterology at Michael E. DeBakey VA Medical Center, both in Houston, Texas. “Although it’s a very exciting time with more options in the last few years for treating UC, even inhibitors with new agents such as JAK inhibitors and interleukin 23 antagonists, many patients have no or only a partial response,” he said in an interview. “Targeting molecules, which has been studied for decades, may offer more than a shot in the dark.”
Why Target TL1A?
Genome-wide studies have shown elevated TL1A, a member of the tumor necrosis factor superfamily, in patients with inflammatory bowel disease (IBD).
“The interaction of TL1A and its ligand, death domain receptor 3, contributes to the immune-mediated inflammation and fibrosis seen in IBD through the downstream production of proinflammatory cytokines by multiple different immune cells, and the elaboration of collagen by fibroblasts,” Dr. Sands explained.
With the intention of targeting TL1A, his group randomly assigned patients with moderate to severe active UC who were glucocorticoid dependent or had not responded to conventional or advanced therapies, with disease extending a minimum of 15 cm from the anal verge. Across arms, the age of the mainly White, non-Hispanic participants ranged from about 37 to about 42, 35%-53% were female, and disease duration was approximately 6-8 years.
The arms received either placebo or intravenous tulisokibart at 1000 mg on day 1 and 500 mg at weeks 2, 6, and 10. Cohort 1 included patients regardless of biomarker status for likelihood of response. Cohort 2 included only patients with a positive test for likelihood of response.
Dr. Hou was surprised that response to tulisokibart vs placebo was not greater in test-identified probable responders. “The biomarker didn’t make a huge difference, just a numerical one,” he said. “It may be that more genes are involved than the test could identify, and response is more complicated. Or perhaps the placebo response was particularly high in this small group. We need a deeper dive into why.”
Earlier Application?
“This was a phase 2 study, so it’s too soon to say if tulisokibart could be used as early therapy or in severe disease,” Sands said. “However, the excellent safety profile and efficacy suggest that these populations should be explored in later studies.
Further work is needed to validate the test to predict higher likelihood of response, he added, and recruiting for a phase 3 study is now underway.
The study was supported by Prometheus Biosciences, a subsidiary of Merck. Dr. Sands disclosed multiple ties to private companies, including research support, consulting, data safety monitoring, travel, a gift, and a stock option. Several coauthors reported, variously, research support from and/or consulting for multiple private companies. Others reported employment, variously, with Prometheus and/or Merck, Spyre Therapeutics, and Mirador Therapeutics, or patent holding for IBD drugs. Dr. Hou had no relevant competing interests to disclose but will participate in the phase 3 trial.
A version of this article appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
In Crohn’s Disease, Early Anti-TNF Levels May be Crucial
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
“The relationship between drug concentrations, immunogenicity and clinical response is likely to be multidirectional; as an observational study, we cannot definitively show the low drug levels are causative. However, our data are consistent with those from elsewhere and confirm the importance of achieving good drug levels to maximize the chances of success with anti-TNF therapy,” said Nicholas Kennedy, MBBS, PhD, a consultant gastroenterologist at Royal Devon University Healthcare NHS Foundation Trust, Exeter, United Kingdom, and coauthor of the study published in The Lancet Gastroenterology & Hepatology .
“We also showed that adequate dosing of thiopurines was needed to prevent immunogenicity, along the lines typically used to treat Crohn’s disease rather than the lower doses sometimes proposed,” he added.
The findings come from the Personalized Anti-TNF Therapy in Crohn’s Disease (PANTS) study conducted in the UK, which included 955 patients treated with infliximab and 655 treated with adalimumab between March 2014 and September 2017. The participants were 6 years or older, the median age was 32.5 years, and 51% were female.
The latest findings come from a 2-year extension of the original 1-year PANTS study, published in 2019, which found that low drug concentrations predicted anti-TNF treatment failure — a result likely attributable in part to immunogenicity, since low-drug concentrations predicted the presence of anti-drug antibodies, and anti-drug antibodies in turn predicted low drug concentrations, according to Miguel Regueiro, MD, AGAF, chief of the Digestive Diseases Institute and a professor of medicine at the Cleveland Clinic, Ohio.
“This is one of the more important studies looking at the longitudinal care of patients with Crohn’s disease on infliximab and adalimumab,” said Dr. Regueiro, who was not involved with the study.
The extension study found that anti-drug antibodies and undetectable drug levels were associated with both treatment without an accompanying immunomodulator and carriage of the HLA-DQA1*05 genetic risk factor, though the latter was true only for treatment with infliximab.
Dr. Regueiro noted that the study demonstrates that “getting it right in induction is probably the most important part” of treating Crohn’s disease.
“Getting patients in remission early has probably a long-term prediction [of treatment success]. I do think that is practice changing. My practice has changed over the years, largely based on the initial PANTS study. I am measuring infliximab and adalimumab levels after induction, and I am using that number to decide if I dose intensify the drug, or if I’ve hit that sweet spot,” said Dr. Regueiro.
The study highlights a debate among clinicians, about whether higher drug levels are associated with remission because of the effects of higher doses, or because patients who respond have reduced leakiness in the gut, leading to greater retention of protein therapeutics.
“What the study clearly says is that the drug [level] after induction is important. It implies that there are higher remission rates early. The only thing that it didn’t really tell you is the total inflammatory burden in the body, and [if] lower inflammation equals higher drug level,” said Dr. Regueiro. He did note that the study found that obesity was a negative predictor of long-term remission, which could be attributable to the pro-inflammatory nature of adipose tissue, but he emphasized that the new study doesn’t prove causation.
The study also emphasizes the importance of the HLA-DQA1*05 genetic risk factor.
“I think it confirms that if you’re a carrier of that HLA-DQA1*05, especially with infliximab, if you’re not on an immunomodulator like a thiopurine, you have a very high likelihood of having very high antibodies against infliximab,” Dr. Regueiro said. “The long-term rates bear that out, meaning if you have one of those carriers and you’re not on a thiopurine, the likelihood of having 3-year success on infliximab — to a lesser degree, adalimumab — is very, very low.”
After exclusion of patients who had no initial response, among infliximab patients, the loss of response was 34.4% at 1 year (95% CI, 30.4-38.2%), 54.5% at 2 years (95% CI, 49.4-59%), and 60% at 3 years (95% CI, 54.1-65.2%). For adalimumab, the loss of response rates were 32.1% (95% CI, 26.7-37.1%), 47.2% (95% CI, 40.2-53.4%), and 68.4% (95% CI, 50.9-79.7%), respectively.
Drug concentrations were measured at week 14, and concentration ranges of 6.1-10 mg/L for infliximab and 10.1-12 mg/L for adalimumab were associated with remission at year 2 (infliximab odds ratio [OR], 2.2; 95% CI, 1.38-3.56. Adalimumab OR, 3.65; 95% CI, 1.83-8.67) and year 3 (infliximab OR, 1.89; 95% CI, 1.16-3.11; adalimumab OR, 6.15; 95% CI, 2.5-23.19). A multivariate analysis found that each ten-fold increase in drug concentration at week 14 predicted lower odds of loss of response at year 2 or 3, both for infliximab (hazard ratio [HR], 0.45; 95% CI, 0.3-0.67) and adalimumab (HR, 0.39; 95% CI, 0.22-0.7).
Among patients taking infliximab, loss of response at year 2 or 3 was associated with female sex (HR, 1.47; 95% CI, 1.11-1.95) and obesity (HR, 1.62; 95% CI, 1.08-2.42). After the researchers controlled for week 14 drug and antibody concentrations, as well as interaction between baseline immunomodulator and HLA-DQA1*05 risk variant, low thiopurine dose was associated with a higher risk of loss of response.
In the adalimumab group, there was an association between presence of the HLA-DQA1*05 risk variant and loss of response (HR, 1.95; 95% CI, 1.17-3.25).
Use of the anti-TNF drug without an immunomodulator was associated with development of anti-drug antibodies for infliximab (HR, 0.4; 95% CI, 0.31-0.52) and adalimumab (HR, 0.42; 95% CI, 0.24-0.75). Development of anti-drug antibodies was also associated with the presence of HLA-DQA1*05 for infliximab (HR, 1.46; 95% CI, 1.13-1.88), but not adalimumab (HR, 1.6; 95% CI, 0.92-2.77). Use of an immunomodulator the day before or day of treatment with infliximab was associated with a delay in development of anti-drug antibodies and undetectable drug concentrations compared to only infliximab (HR, 2.87; 95% CI, 2.2-3.74) and to use of the immunomodulator following infliximab treatment (HR, 1.7; 95% CI, 1.11-2.59).
“We suggest aiming to start thiopurines alongside infliximab; our data suggest that later introduction is less effective,” said Dr. Kennedy, who is currently chair of the British Society of Gastroenterology IBD Clinical Research Group.
Dr. Kennedy reported institutional grants or contracts, personal consulting fees, and personal payments or honoraria from a variety of pharmaceutical companies. See the original article for a complete list.
Dr. Regueiro reported that he has been on advisory boards and consulted for Abbvie, Janssen, UCB, Takeda, Pfizer, BMS, Organon, Amgen, Genentech, Gilead, Salix, Prometheus, Lilly, Celgene, Boehringer Ingelheim Pharmaceuticals Inc. (BIPI), Celltrion, and Roche.
A version of this article appeared on Medscape.com.
Environmental Pollutants Play a Growing Role in IBD
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
The culprit environmental substances include heavy and transition metals, air pollutants, pesticides, and industrial contaminants. The latter encompass synthetic chemicals such as perfluoroalkyls and polyfluoroalkyls (PFAs), which are present in many common household products.
In contrast, zinc exposure may have a protective, anti-inflammatory effect, according to a research group led by Maria Manuela Estevinho, MD, of the Department of Gastroenterology of the Unidade Local de Saúde Gaia e Espinho in Vila Nova de Gaia, Portugal.
Published in Gut , the review also found limited data suggesting adverse IBD outcomes such as hospitalizations are more prevalent with increased exposure to air contaminants in particular.
“These data carry relevance toward counseling patients and family members,” coauthor Manasi Agrawal, MD, assistant professor of medicine at the Icahn School of Medicine, Mount Sinai, and a gastroenterologist at Mount Sinai Hospital in New York City, said in an interview. “At the individual level, we can try to decrease our exposure to chemicals; for example, to minimize use of pesticides and products containing in our homes. However, at the broader community level, health policy changes are needed to help with mitigation strategies and curb production.”
The physiological mechanisms by which pollutants raise IBD risk include an exaggerated immune response leading to systemic inflammation, loss of tight junction proteins leading to increased gut permeability, and dysbiosis of the intestinal microbiota.
The review found the following effects for various pollutants:
- Heavy and transition metals such as copper, lead, and cadmium were associated with gut dysbiosis, overgrowth of undesirable species of microorganisms, and loss of tight junction proteins leading to leaky gut. In all studies, individuals with IBD showed higher concentrations of such metals than healthy control individuals. While the specific profile of heavy metals varied across studies, lead, copper, and iron, were linked to IBD risk in more than one study.
- The particulate matter present in air pollution — including agricultural and wood dust as well as volcanic ash and hydrocarbon dioxin — was linked to dysbiosis and tight junction protein loss. Air pollution has also been linked to increased incidence of irritable bowel syndrome.
- Industrial and organic pollutants such as perfluoroalkyl and polyfluoroalkyl compounds, triclocarban, and polychlorinated biphenyls were also associated with gut permeability and/or reduced microbial diversity.
- Pesticides such as PFAs, organochloride and organophosphate compounds, and pyrethroids were associated with loss of tight junction proteins.
- Zinc was linked to an increase in tight junction proteins.
Commenting on the review but not involved in it, Ashwin N. Ananthakrishnan, MBBS, MD, MPH, AGAF, director of the Crohn’s and Colitis Center at Massachusetts General Hospital, and associate professor at Harvard Medical School in Boston, called it a very important study that expands our understanding of the role of environment in IBD.
“While traditionally studies have focused on dietary and other exposures related to personal behavior and lifestyle such as smoking, this expands consideration to exposures at the environmental level, where an individual may have less control,” he said in an interview.
“This shift could be critically important from a policy standpoint as modifying these risk factors may require more societal than individual efforts,” he added. He did offer a caveat, however. “While the review highlights several plausible associations, all of which merit further study, importantly, one should also avoid overinterpreting the results as there are very few high-quality studies that provide robust evidence of an association. So more work is needed.”
Recent research has suggested that environmental exposures affect IBD risk more than genetic predisposition.
As background to this review, the growing industrialization and consumerism of the developing world has seen the global number of IBD cases rise from 3.3 million in 1990 to an estimated 4.9 million in 2019, a jump of 47.5%. In the United States, IBD accounts for more than $25 billion in direct healthcare costs.
In terms of the near future, Dr. Agrawal said, “Next steps would be to measure various chemicals in pre-disease biological samples for objective assessment of the impact of chemicals on IBD risk, and such studies are already underway.”
That would mean using exposure biomarkers with high temporal resolution in preclinical samples, as well as advanced measurement techniques and machine-based composite data analysis to explain the IBD-pollutant relationship. “This approach may also provide insight into the role of different environmental insults in different stages of life and clarify whether the timing of exposure may be more critical than the duration,” the authors wrote.
Dr. Agrawal was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the International Organization For the Study of Inflammatory Bowel Disease, and the Crohn’s and Colitis Foundation. She reported consulting for Douglas Pharmaceuticals. Other authors reported lecture/consulting fees from multiple pharmaceutical/biomedical companies. Dr. Ananthakrishnan had no relevant conflicts of interest.
A version of this article appeared on Medscape.com.