IBD & Intestinal Disorders

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.

“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.

The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
 

Clinical Implications, Not Applications

The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.

Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.

But lack of scientific evidence and validity hasn’t stopped a growing number of companies across the globe from offering direct-to-consumer (DTC) microbiome tests, Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.

“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”

Dr. von Rosenvinge and colleagues authored a recent article in Science  arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
 

Unreliable, Unregulated

The lack of reliability has been shown by experts who have tested the tests.

“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”

Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.

“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).

Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.

The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.

“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.

Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:

• Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
• Gaining insight into the interactions among the identified pathogens.
• Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
• Creating a prototype formulation for testing.
• Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
• Conducting clinical testing.

Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
 

Potential Pitfalls

Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”

“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”

Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.

“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.

Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
 

What to Tell Patients

“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.

“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”

Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”

When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.

“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”

Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”

She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
 

Educate Clinicians, Companies

More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.

“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.

“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.

As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”

Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.

“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.

Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the subcutaneous administration of vedolizumab (Entyvio) for maintenance therapy in adults with moderately to severely active Crohn’s disease (CD) after induction therapy with intravenous (IV) vedolizumab. 

The move follows the FDA’s approval last year of subcutaneous vedolizumab for maintenance treatment of adults with moderately to severely active ulcerative colitis (UC). 

The humanized immunoglobulin G1 monoclonal antibody is available as a single-dose prefilled pen (Entyvio Pen).

The FDA first approved the IV formulation of the biologic in 2014 for patients with moderate to severe UC and CD who cannot tolerate other therapies or in whom such therapies have failed. 

The approval of subcutaneous vedolizumab for maintenance treatment of CD is based on the phase 3, randomized, double-blind, placebo-controlled VISIBLE 2 trial.

The trial enrolled 409 adult patients with moderately to severely active CD who had clinical response at week 6 following two doses of open-label IV vedolizumab at weeks 0 and 2. 

At week 6, they were randomly allocated in a 2:1 ratio to receive vedolizumab 108 mg administered by subcutaneous injection or placebo every 2 weeks. The primary endpoint was clinical remission at week 52, which was defined as a total Crohn’s Disease Activity Index score ≤ 150.

The results showed that significantly more patients receiving subcutaneous vedolizumab than placebo achieved long-term clinical remission (48% vs 34%; P < .01), the company said in a news release. 

The safety profile of subcutaneous vedolizumab is generally consistent with the known safety profile of IV vedolizumab, with the addition of injection-site reactions (including injection-site erythema, rash, pruritus, swelling, bruising, hematoma, pain, urticaria, and edema).

“Crohn’s disease is a complex and usually progressive disease for which an appropriate management plan is critical. My primary goal as a clinician is always to get patients to achieve remission,” Timothy Ritter, MD, senior medical director, GI Alliance Research, and assistant professor of medicine, Burnett School of Medicine at TCU, Fort Worth, Texas, said in the news release.

GI Alliance

A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.

The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?

Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.

IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.

While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
 

Microbiota in IBS 

Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota. 

Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use. 

This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.

Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.

In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.

Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.

Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
 

Recent Guideline 

In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.

Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
 

Efficacy and Availability 

Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.

Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.

“Probiotic efficacy largely depends on the bacterial species, strain, and clinical situation treated. Only probiotics with demonstrated clinical efficacy in randomized placebo-controlled trials should be recommended,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
 

Effective Probiotics 

B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.

L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.

The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.

B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.

“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”

Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
 

Mechanisms of Action 

In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.

Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).

B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.

B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.

Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).

Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.

Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Histologic inflammation in women with inflammatory bowel disease (IBD) may lead to reduced fertility, according to a Swedish nationwide cohort study.

Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.

“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”

Courtesy University of Gothenburg

Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.

This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).

“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”

Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.

Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.

“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”

The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.

“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”

The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.

Histologic inflammation in women with inflammatory bowel disease (IBD) may lead to reduced fertility, according to a Swedish nationwide cohort study.

Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.

“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”

Courtesy University of Gothenburg

Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.

This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).

“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”

Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.

Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.

“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”

The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.

“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”

The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.

Histologic inflammation in women with inflammatory bowel disease (IBD) may lead to reduced fertility, according to a Swedish nationwide cohort study.

Reduced fertility was linked with histologic inflammation even in the absence of clinical disease activity, highlighting the importance of achieving deep remission in women planning pregnancy, reported lead author Karl Mårild, MD, PhD, of Sahlgrenska Academy, Gothenburg, Sweden, and colleagues.

“Reduced female fertility (ie, number of live births) is believed to be primarily confined to women with clinically active IBD, especially in Crohn’s disease (CD), where symptoms may inhibit sexual activity, and inflammation may affect the fallopian tubes and ovaries,” the investigators wrote in Gastroenterology. “Despite the increasing appreciation of histologic activity in IBD, its association with female fertility has not been clarified, including whether histologic activity in the absence of clinical disease activity impairs fertility.”

Courtesy University of Gothenburg

Dr. Mårild and colleagues aimed to address this knowledge gap by analyzing fertility rates and histologic inflammation or IBD activity in two cohorts of women with IBD aged 15-44 years. The first group included approximately 21,000 women with and without histologic inflammation from 1990 to 2016. The second group included approximately 25,000 women with or without IBD clinical activity from 2006 to 2020. In each group, the relationship between fertility and IBD was compared with fertility in matched general population comparator individuals.

This approach showed that clinical IBD activity was associated with an adjusted fertility rate ratio (aFRR) of 0.76 (95% CI, 0.72-0.79), which equates to one fewer child per six women with 10 years of clinical activity. Impacts on fertility were similar for UC (aFRR, 0.75) and CD (aFRR, 0.76).

“Fertility rates were notably reduced during periods of clinical IBD activity and, contrary to a generally accepted belief, equally reduced in clinically active UC and CD,” the investigators wrote. “Besides inflammation, clinically active IBD may reduce fertility through psychological mechanisms (eg, depression), dyspareunia (especially in perianal CD), bowel pain, urgency, and other symptoms that hinder sexual activity.”

Compared with histologic remission, histologic inflammation was also associated with reduced fertility (aFRR, 0.90). This means that in periods of histologic inflammation, 6.35 live births occurred per 100 person-years of follow-up, compared with 7.09 lives births for periods of histologic remission. This amounts to one fewer child per 14 women with 10 years of histologic inflammation.

Finally, the study revealed that, in women with clinically quiescent IBD, those with histologic inflammation had significantly reduced fertility, compared with those in histologic remission (aFRR, 0.85). This association persisted after controlling for contraceptive use.

“Even if histologic inflammation was associated with an overall modest fertility reduction … its impact on the individual might be substantial, with potential ramifications beyond reproductive health, given that reduced female fertility is linked to poor quality of life and mental health,” Dr. Mårild and colleagues wrote. “At a societal level, involuntary childlessness causes high and increasing costs, highlighting the need to focus on preventable causes of reduced fertility.”

The investigators suggested that inflammation may be driving infertility by reducing ovulation and fertilization, or by reducing endometrial receptivity, which increases risk of pregnancy loss.

“This is the first study, to our knowledge, to show reduced fertility during histologic inflammation in IBD compared to histologic remission,” the investigators wrote. “Our findings suggest that achieving histologic remission may improve the fertility of women with IBD, even in the absence of clinically defined disease activity.”

The investigators disclosed relationships with AbbVie, Pfizer, Janssen, and others.

Colonoscopy with computer-aided detection (CADe) fails to improve adenoma detection rate (ADR) in real-world, nonrandomized trials, according to investigators.

Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.

CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”

RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.

The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.

University of Kansas Medical Center

“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”

This approach revealed less favorable outcomes than those reported by RCTs.

CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).

“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.

While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.

Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).

Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.

“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”

Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.

“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.

This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.

Colonoscopy with computer-aided detection (CADe) fails to improve adenoma detection rate (ADR) in real-world, nonrandomized trials, according to investigators.

Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.

CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”

RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.

The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.

University of Kansas Medical Center

“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”

This approach revealed less favorable outcomes than those reported by RCTs.

CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).

“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.

While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.

Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).

Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.

“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”

Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.

“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.

This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.

Colonoscopy with computer-aided detection (CADe) fails to improve adenoma detection rate (ADR) in real-world, nonrandomized trials, according to investigators.

Although CADe did not increase burden of colonoscopy in the real-world, these real-world detection rates casts doubt on the generalizability of positive findings from randomized trials, reported lead author Harsh K. Patel, MD, of the University of Kansas Medical Center, Kansas City, Missouri, and colleagues.

CADe-assisted colonoscopy has gained increasing attention for its potential to improve ADR, particularly with the recent publication of a meta-analysis involving 20 randomized controlled trials (RCTs), Dr. Patel and colleagues wrote in Clinical Gastroenterology and Hepatology. “However, results of RCTs are not necessarily reproducible in clinical practice.”

RCTs evaluating this technology are susceptible to various issues with validity, they noted, such as psychological bias stemming from lack of blinding to the possibility that CADe could reduce operator attention, paradoxically “deskilling” endoscopists.

The present meta-analysis aimed to overcome these potential shortfalls by analyzing nonrandomized data from eight studies involving 9,782 patients.

University of Kansas Medical Center

“The lack of a highly controlled setting reduces the psychological pressure of the endoscopists to demonstrate a possible benefit of CADe (i.e., the operator bias) and allows endoscopists to use CADe according to their preferences and attitudes which we usually experience in a real-world clinical practice,” the investigators wrote. “On the other hand, noncontrolled factors may affect the outcome of the study, especially when considering that an equivalent distribution of prevalence of disease is required for a fair assessment of the effectiveness of the intervention.”

This approach revealed less favorable outcomes than those reported by RCTs.

CADe-assisted ADR was not significantly different from ADR for standard colonoscopy (44% vs 38%; risk ratio, 1.11; 95% CI, 0.97-1.28), nor was mean number of adenomas detected per colonoscopy (0.93 vs 0.79; mean difference, 0.14; 95% CI, -0.04-0.32).

“Our study provides a contrasting perspective to those results previously known from the randomized studies,” the investigators wrote.

While detection benefits were not identified, burden of CADe-assisted colonoscopy was not elevated either.

Mean nonneoplastic lesions per colonoscopy was similar between modalities (0.52 vs 0.47; mean difference, 0.14; 95% CI, -0.07-0.34), as was withdrawal time (14.3 vs 13.4 minutes; mean difference, 0.8 minutes; 95% CI, -0.18-1.90).

Dr. Patel and colleagues described “a high level of heterogeneity that was qualitatively and quantitatively distinct from the heterogeneity discovered in the prior meta-analysis of RCTs.” Unlike the RCT meta-analysis, which had no studies with an ADR outcome favoring the control arm, the present meta-analysis found that one third of the included studies favored the control arm.

“This qualitative difference generates a much higher degree of ambiguity, as it does not apply only to the magnitude of the effect of CADe, but it puts in question the actual existence of any CADe-related benefit,” they wrote. “An important point to make is that the analysis of adenoma and serrated lesions per colonoscopy supported the qualitative heterogeneity, favoring the control arm over the CADe arm, in the direction of the effect.”

Dr. Patel and colleagues suggested that the concurrent lack of benefit and lack of harm associated with CADe in the present meta-analysis is “interesting,” and may point to underutilization or a lack of effect of CADe.

“To address the uncertainties in the current literature, we recommend conducting additional randomized studies in a more pragmatic setting,” they concluded.

This meta-analysis was supported by the European Commission and AIRC. The investigators disclosed relationships with NEC, Satisfy, Odin, and others.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Children and adolescents with functional constipation showed significantly greater increases in spontaneous bowel movements with linaclotide compared with placebo, according to data from 330 individuals.

“Functional constipation is prevalent in pediatrics and is associated with chronic burdensome symptoms and impaired quality of life with an unmet need for treatment options for this age group,” corresponding study author Julie Khlevner, MD, AGAF, a pediatric gastroenterologist at Columbia University Vagelos College of Physicians and Surgeons, New York, said in an interview.

Jörg Meyer

“Linaclotide has been approved for adults with chronic idiopathic constipation and irritable bowel syndrome with constipation, but its efficacy and safety in pediatric patients were unknown. Therefore, evaluating its use in this population was crucial to provide evidence-based treatment option,” she said.

In a study published in The Lancet Gastroenterology & Hepatology, the researchers randomized 166 pediatric patients with functional constipation to 72 micrograms of linaclotide once daily for 12 weeks and 164 to a placebo. The study was conducted at 64 clinic or hospital sites across 7 countries between October 1, 2019, and March 21, 2022. Approximately half (55%) of the patients were female.

The primary outcome was a change from baseline to 12 weeks in the frequency of spontaneous bowel movements (SBMs) per week, with no rescue medication on the day of or before the bowel movement. The secondary endpoint was change in stool consistency from baseline to 12 weeks. The mean frequency for SBMs at baseline was 1.16 per week in patients randomized to linaclotide and 1.28 for those randomized to placebo; these rates increased to 3.41 and 2.29, respectively, over the study period. The linaclotide patients showed a significantly greater improvement over placebo patients based on least-squares mean change from baseline (2.22 vs. 1.05, P = .0001).

In a subgroup analysis by age, the response was stronger in younger patients aged 6-11 years than in those aged 12-17 years, the researchers noted. This difference might stem from different pathophysiological mechanisms between older and younger ages, such as withholding behavior, they added.

Linaclotide was well tolerated overall; the most frequently reported treatment-emergent events were diarrhea (seven linaclotide patients and three placebo patients). In addition, five linaclotide patients and four placebo patients developed COVID-19 during treatment. No deaths occurred during the study, but one serious adverse event involving severe diarrhea, dehydration, and hospitalization, occurred in a 17-year-old female patient, but resolved after administration of intravenous fluids, the researchers noted.
 

Clinical Implications and Next Steps

The study findings reflect previous research on linaclotide in adults, Dr. Khlevner said. “The significant improvement in spontaneous bowel movements frequency and stool consistency with linaclotide compared to placebo is consistent with its mechanism of action as a guanylate cyclase C agonist,” she noted.

In clinical practice, barriers to the use of linaclotide may include lack of awareness of linaclotide’s safety and efficacy profile, and of its Food and Drug Administration approval for use in children aged 6-17 years with functional constipation, said Dr. Khlevner. “Additionally, access to the medication and insurance coverage may be potential barriers for some patients.” However, “some of these barriers can be overcome through education and training of healthcare providers regarding the appropriate use of linaclotide in pediatric patients with functional constipation,” she added.

The findings were limited by several factors including potential measurement bias and selection bias, lack of assessment of lifestyle modifications as confounding factors, and lack of quality-of-life assessment, the researchers noted. Other limitations included the relatively short 12-week treatment duration, which may not fully capture long-term safety and efficacy, and the focus on patients aged 6-17 years, Dr. Khlevner told this news organization.

“Future research could address these limitations through longer-term studies with broader age ranges and incorporating patient-reported outcomes in real world situations to assess the overall impact of linaclotide treatment on pediatric patients with functional constipation,” she said.

Study Supports Noninvasive Treatment Option

An alternative medication for children with functional constipation who do not respond to current therapies could prevent the use of more invasive interventions such as frequent enemas or antegrade enemas, Stephen M. Borowitz, MD, professor of pediatrics at the University of Virginia, Charlottesville, said in an interview.

Dr. Borowitz said he was not surprised by study findings. “Given the mechanism of action of the drug, I would expect the majority of children with functional constipation to respond in the sense of having more frequent and softer stools,” he said. “The bigger question, which wasn’t answered, is whether children who fail more conservative therapies respond to linaclotide,” said Dr. Borowitz, who was not involved in the study. “This was a phase 3 trial of otherwise healthy children with functional constipation and we know the majority of these children will respond to aggressive management with osmotic stool softeners, plus or minus a stimulant like senna coupled with lifestyle modifications (such as drinking more fluid, regular toileting, and appropriate toileting behaviors),” he said.

The greatest short-term barrier to the expanded use of linaclotide in clinical practice will likely be cost, and whether insurance will cover the drug, Dr. Borowitz told this news organization. Insurance coverage may not be an option until the child has failed more conservative, less expensive therapies, he said.

Also, the current study was a placebo-controlled trial, and not a comparison between linaclotide and polyethylene glycol, plus or minus senna, with other routine interventions, he said.

Looking ahead, “now that we know linaclotide is better than placebo, we need to know if it is as good, better, or worse than other proven interventions, and perhaps even more importantly, is it effective among children who have failed more conservative management,” Dr. Borowitz said. “We also need to know long-term risks, and given that the majority of childhood constipation develops before age 6 years, whether the drug can be used in younger children,” he emphasized. If so, studies need to examine whether linaclotide alters the natural history of the problem, he added. Previous studies suggest that the longer the symptom goes on, the harder it is to undo the secondary behaviors that result, such as withholding, pelvic floor dysfunction, and toileting refusal, he noted.

The study was supported by AbbVie and Ironwood Pharmaceuticals. The lead author, Carlo Di Lorenzo, MD, disclosed consulting fees from AbbVie, Ironwood Pharmaceuticals, Mallinckrodt, NeurAxis, QOL Medical, and Takeda. Dr. Khlevner disclosed honoraria from Abbott Pediatric Nutrition and participation on a data safety monitoring board and advisory board for AbbVie. Dr. Borowitz had no financial conflicts to disclose.

Blood-based screening for colorectal cancer (CRC), also known as a “liquid biopsy,” may be better than nothing among patients who skip established screening tests, but it can’t replace colonoscopy as the gold standard, according to two new modeling studies and an expert consensus commentary.

Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.

AGA Institute

The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.

The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.

Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
 

Comparing CRC Screening Methods

In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.

Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).

However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.

In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.

Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.

Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.

Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.

“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
 

Additional Considerations

The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.

However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.

In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.

Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.

Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.

Blood-based screening for colorectal cancer (CRC), also known as a “liquid biopsy,” may be better than nothing among patients who skip established screening tests, but it can’t replace colonoscopy as the gold standard, according to two new modeling studies and an expert consensus commentary.

Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.

AGA Institute

The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.

The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.

Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
 

Comparing CRC Screening Methods

In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.

Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).

However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.

In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.

Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.

Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.

Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.

“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
 

Additional Considerations

The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.

However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.

In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.

Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.

Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.

Blood-based screening for colorectal cancer (CRC), also known as a “liquid biopsy,” may be better than nothing among patients who skip established screening tests, but it can’t replace colonoscopy as the gold standard, according to two new modeling studies and an expert consensus commentary.

Although some patients find blood-based tests more convenient, the higher numbers of false positives and false negatives could lead to more CRC cases and deaths.

“Based on their current characteristics, blood tests should not be recommended to replace established colorectal cancer screening tests, since blood tests are neither as effective nor cost-effective and would worsen outcomes,” David Lieberman, MD, AGAF, chair of the American Gastroenterological Association’s CRC Workshop Panel, and lead author of the expert commentary, said in a statement.

AGA Institute

The blood tests detect circulating nucleotides, such as cell-free DNA or metabolic products associated with CRC and its precursors. Current tests are in development by Guardant Health and Freenome.

The two modeling studies, published in Gastroenterology on March 26, analyzed the effectiveness and cost-effectiveness of blood-based CRC screening that meets Centers for Medicare & Medicaid Services (CMS) coverage criteria, as well as the comparative effectiveness and cost-effectiveness of CRC screening with blood-based biomarkers versus fecal tests or colonoscopy.

Also published on March 26 in Clinical Gastroenterology and Hepatology, the expert commentary included key conclusions from the AGA CRC Workshop, which analyzed the two modeling studies.
 

Comparing CRC Screening Methods

In the first modeling study, an international team of researchers ran three microsimulation models for CRC to estimate the effectiveness and cost-effectiveness of triennial blood-based screening for ages 45-75, compared with no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with a FIT assay, and colonoscopy screening every 10 years. The researchers used CMS coverage criteria for blood tests, with a sensitivity of at least 74% for detection of CRC and specificity of at least 90%.

Without screening, the models predicted between 77 and 88 CRC cases and between 32 and 36 deaths per 1,000 individuals, costing between $5.3 million to $5.8 million. Compared with no screening, blood-based screening was considered cost-effective, with an additional cost of $25,600 to $43,700 per quality-adjusted life-year gained (QALYG).

However, compared with the FIT, stool, and colonoscopy options, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT was more effective and less costly, with 5-24 QALYG and nearly $3.5 million cheaper than blood-based screening, even when blood-based uptake was 20 percentage points higher than FIT uptake.

In the second modeling study, US researchers compared triennial blood-based screening with established alternatives at the CMS thresholds of 74% sensitivity and 90% specificity.

Overall, a blood-based test at the CMS minimum reduced CRC incidence by 40% and CRC mortality by 52% versus no screening. However, a blood-based test was significantly less effective than triennial stool DNA testing, annual FIT, and colonoscopy every 10 years, which reduced CRC incidence by 68%-79% and CRC mortality by 73%-81%.

Assuming a blood-based test would cost the same as a multi-target stool test, the blood-based test would cost $28,500 per QALYG versus no screening. At the same time, FIT, colonoscopy, and stool DNA testing were less costly and more effective. In general, the blood-based test would match FIT’s clinical outcomes if it achieved 1.4- to 1.8-fold the participation rate for FIT.

Even still, the sensitivity for advanced precancerous lesion (APL) was a key determinant. A paradigm-changing blood-based test would need to have higher than 90% sensitivity for CRC and 80% for APL, 90% specificity, and cost less than $120 to $140, the study authors wrote.

“High APL sensitivity, which can result in CRC prevention, should be a top priority for screening test developers,” the authors wrote. “APL detection should not be penalized by a definition of test specificity that focuses on CRC only.”
 

Additional Considerations

The AGA CRC Workshop Panel met in September 2023 to review the two modeling studies and other data on blood-based tests for CRC. Overall, the group concluded that a triennial blood test that meets minimal CMS criteria would likely result in better outcomes than no screening and provide a simple process to encourage more people to participate in screening.

However, patients who may have declined colonoscopy should understand the need for a colonoscopy if blood-based tests show abnormal results, the commentary authors wrote.

In addition, because blood-based tests for CRC appear to be less effective and more costly than current screening options, they shouldn’t be recommended to replace established screening methods. Although these blood-based tests may improve screening rates and outcomes in unscreened people, substituting blood tests for other effective tests would increase costs and worsen patient outcomes.

Beyond that, they wrote, the industry should consider other potential benchmarks for an effective blood test, such as a sensitivity for stage I-III CRC of greater than 90% and sensitivity for advanced adenomas of 40%-50% or higher.

University of California San Diego

“Unless we have the expectation of high sensitivity and specificity, blood-based colorectal cancer tests could lead to false positive and false negative results, which are both bad for patient outcomes,” John M. Carethers, MD, AGAF, vice chancellor for health sciences at UC San Diego, AGA past president, and a member of the AGA CRC Workshop panel, said in a statement.

Several authors reported consultant roles and funding support from numerous companies, including Guardant Health and Freenome.

Placebo responses in patients with irritable bowel syndrome (IBS) may be altered by baseline beliefs and the patient-provider relationship, according to investigators.

These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.

“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”

While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.

University of Buffalo

Placebo responses in patients with irritable bowel syndrome (IBS) may be altered by baseline beliefs and the patient-provider relationship, according to investigators.

These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.

“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”

While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.

University of Buffalo

Placebo responses in patients with irritable bowel syndrome (IBS) may be altered by baseline beliefs and the patient-provider relationship, according to investigators.

These findings may improve prediction of placebo responses in IBS, and may help avoid patient-provider “mismatch,” both of which can alter treatment outcomes and confound clinical trial findings, reported lead author Jeffrey M. Lackner, PsyD, chief of the division of behavioral medicine at the University of Buffalo, New York, and colleagues.

“A relatively large (40%) placebo response in IBS trials obscures potentially useful, mechanistic, and pharmacodynamically induced symptom changes among agents that do reach market,” the investigators wrote in Gastro Hep Advances. “This begs the question of what individual difference factors distinguish placebo responders.”

While previous studies have explored placebo patient predictors in IBS, most focused on study design and baseline personal characteristics such as age and sex, with none yielding prognostically reliable findings, according to Dr. Lackner and colleagues. Mid-treatment factors such as patient-provider dynamics have not been featured in published meta-analyses, they noted, despite their potential importance.

University of Buffalo

Crohn’s disease (CD) involves altered B-cell expansion and maturation in draining mesenteric lymph nodes, according to investigators.

These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.

Medical University of Vienna

“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”

Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.

To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.

First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.

The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.

Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.

Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.

Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.

Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.

BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.

“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”

The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.

Crohn’s disease (CD) involves altered B-cell expansion and maturation in draining mesenteric lymph nodes, according to investigators.

These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.

Medical University of Vienna

“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”

Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.

To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.

First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.

The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.

Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.

Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.

Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.

Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.

BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.

“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”

The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.

Crohn’s disease (CD) involves altered B-cell expansion and maturation in draining mesenteric lymph nodes, according to investigators.

These findings begin to address a knowledge gap in Crohn’s disease that has been more thoroughly explored in ulcerative colitis, reported lead author Sonja Kappel-Latif, MD, PhD, of Medical University of Vienna, Vienna, Austria, and colleagues.

Medical University of Vienna

“Recent studies have investigated the role of B-cell responses in ulcerative colitis, which exclusively affects the colon, whereas data in CD, which mainly affects the terminal ileum, are insufficient,” the investigators wrote in wrote in Cellular and Molecular Gastroenterology and Hepatology. “Granuloma formation within the thickened, inflamed mesentery of patients with CD, however, is associated with significantly worse outcome, and microstructural analysis has suggested increased numbers of B cells in CD mesentery.”

Previous studies have shown that abnormal B-cell development in patients with CD leads to development of IgG targeting commensal — instead of pathogenic — gut bacteria. Yet B-cell receptor sequencing in CD has only been conducted on peripheral blood, despite awareness that anticommensal IgG antibodies can be transported across mucosal barriers in patients with ulcerative colitis, sustaining intestinal inflammation.

To better characterize local B-cell responses in CD, the investigators evaluated paired samples of draining mesenteric lymph nodes (MLNs) from both healthy and adjacently affected intestinal tissue, yielding a range of findings.

First, the investigators noted that CD19+ B cells and CD45+ leukocytes were expanded in affected MLNs, while T cells were reduced. A closer look showed that IgD-CD27- B cells were more abundant among CD19+CD45+ B cells in affected MLNs. Within this CD45+CD19+CD27+IgD- B-cell fraction, CD38- memory B cells were reduced.

The above findings suggest “ongoing antigenic stimulation within affected MLNs,” the investigators wrote.

Further comparison of paired samples showed that germinal centers (within which B cells mature) were significantly larger in affected MLNs, and contained dark and light zones. In contrast, healthy MLNs had smaller, more immature germinal centers.

Due to T-cell dependence during B-cell isotype switching within these germinal centers, the investigators next conducted immunohistochemistry staining for Bcl6, a “master regulator” of T-follicular helper cells expressed in class-switching B cells, and Ki67, which indicates cell proliferation. These analyses shows that both markers were “highly positive” within the germinal centers of affected MLNs.

Next, Dr. Kappel-Latif and colleagues conducted B-cell receptor (BCR) sequencing to characterize differences in class switching. Compared with healthy MLNs, affected MLNs showed decreased use of IGHA and IGHE alongside a significant uptick in IGHG1/2.

Further analyses showed that somatic hypermutation (SHM) frequency was significantly higher in IGHM and IGHA B cells, which was driven by mutations in complementary determining regions (CDRs) and framework regions of IGHA B cells, and mutations in the CDRs of IGHM B cells.

BCR diversity increased in the IGHG1/2 B cells, but remained unchanged in the IGHM or IGHA B cells.

“Overall, our results indicate ongoing class switching within draining MLNs of affected intestinal segments, with a shift toward IGHG1/2 BCRs,” the investigators concluded. “The lack of high SHM rates within IGHG1/2 BCRs, the difference between IGHA and IGHG1/2 BCRs in single MLNs, and increased diversity in IGHG1/2 BCRs suggests that many antigens do not result in long-lasting immunologic stimulation, and IGHA and IGHG1/2 responses may target different pathogens/commensals.”

The study was supported by the Austrian Science Fund and the Major of Vienna. The investigators disclosed no conflicts of interest.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Brian Strickland/University of North Carolina

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Brian Strickland/University of North Carolina

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.

Based on a synthesis of best available evidence, the American Gastroenterological Association (AGA) has released clinical recommendations on fecal microbiota-based therapies (FMT) in adults with gastrointestinal diseases.

Addressing Clostridium difficile infection (CDI), Crohn’s disease (CD) ulcerative colitis (UC), pouchitis, and irritable bowel syndrome (IBS), the guidance supports FMT for the prevention of recurrent CDI but not for inflammatory bowel disease (IBD) or IBS — outside of clinical trials.

The AGA’s recommendations were published in Gastroenterology.

“Fecal microbiota–based therapies are effective therapy to prevent recurrent C. difficile in select patients,” the AGA guideline states. “Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C. difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.”

“We thought it was important to write this guideline because of the growing number of trials of FMT in IBD and IBS populations. It was also important with the new FDA-approved treatments on the market,” the guideline’s first author, Anne F. Peery, MD, MSCR, AGAF, told this news organization, noting that the recently approved products did not yield better results than those of conventional rectal FMT. “The guidelines will help clinicians understand the available therapies and how to use these treatments,” added Dr. Peery, associate professor in the Division of Gastroenterology and Hepatology at the University of North Carolina School of Medicine in Chapel Hill.

Although the existing evidence is of low or very low certainty, Dr. Peery acknowledged, gastroenterologists “should be comfortable with conventional FMT and also the new FDA-approved products. We spent a considerable amount of time developing implementation considerations, which is practical advice to help clinicians use the guideline recommendations.”

Brian Strickland/University of North Carolina

Recommendations

The eight-member panel suggested the following practices on behalf of the AGA Clinical Guidelines Committee:

• In immunocompetent adults with recurrent CDI, select use of FMT can be used after completion of standard-of-care antibiotics to prevent recurrence. It can be considered after the second recurrence (episode 3) of CDI or in select patients at high risk for either recurrent CDI or a morbid CDI recurrence. Recurrent CDI is defined as clinically significant diarrhea ≥ 3 unformed stools in 24 hours with a confirmatory positive test within 8 weeks of completing antibiotics. Select use includes patients who have recovered from severe, fulminant, or particularly treatment-refractory CDI and patients with significant comorbidities. Severe CDI involves a leukocyte count of ≥15 × 109 cells/L and/or creatinine ≥1.5 mg/dL, while fulminant CDI involves shock, ileus, or megacolon and can be fatal.
• In mildly or moderately immunocompromised adults with recurrent CDI, the guidance recommends select use of conventional fecal microbiota transplant.
• In severely immunocompromised adults or those undergoing cytotoxic treatment, the AGA advises against the use of any fecal microbiota-based therapies to prevent recurrent CDI.
• Conventional FMT is not advised in patients who have bowel perforation or obstruction or are severely immunocompromised.
• For CDI patients not interested in FMT, reasonable alternatives to prevent recurrence are a vancomycin taper, tapered-pulsed fidaxomicin, or bezlotoxumab.
• In adults hospitalized with severe or fulminant CDI not responding to standard-of-care antibiotics, the AGA recommends select use of conventional FM transplant.
• In the current absence of evidence, the guidance advises against the use of conventional fecal microbiota transplant as treatment for IBD or IBS except in the context of clinical trials.

“We felt the data for using FMT in the treatment of UC was promising, but there is still a lot more work to be done in IBD and IBS,” Dr. Peery said. For each disease section the guideline outlined directions for future research. It will be updated in 3-5 years as more evidence becomes available.

This guideline was fully funded by the AGA Institute. Dr. Peery and fellow panel member Dr. Benjamin Lebwohl are supported by grants the National Institute of Diabetes and Digestive and Kidney Diseases. Panel member Colleen R. Kelly, MD, is supported by the National Institute of Allergy and Infectious Diseases.

None of the panel members had any conflicts of interest to report.