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Computer-Aided Colonoscopy Falls Short in Real-World Practice
, 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.
“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.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
The advent of AI in colonoscopy through computer-aided detection (CADe) systems has been promising, with over 20 randomized controlled trials (RCTs) affirming its benefits. However, this enthusiasm has been tempered by several recent nonrandomized studies indicating no real-world advantage, as discussed in Patel et al.’s systematic review and meta-analysis in Clinical Gastroenterology and Hepatology.
In addition, a critical consideration with evaluating any AI/CADe system is they often undergo frequent updates, each promising improved accuracy, sensitivity, and specificity. This is an interesting dilemma and raises questions about the enduring relevance of studies conducted using outdated versions of CADe.
In my opinion, the jury is still out on the effectiveness of CADe for colonoscopy in a real-world setting. The definitive assessment of CADe’s real-world value necessitates larger, well-structured trials that mirror actual clinical environments and span extended periods of time, taking care to minimize biases that may have influenced the results of current published studies.
Nabil M. Mansour, MD, is assistant professor of medicine in the Section of Gastroenterology, Baylor College of Medicine, Houston. He has served as a consultant for Iterative Health.
, 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.
“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.
, 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.
“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.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Linaclotide Succeeds for Functional Constipation in Children
, 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.
“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.
, 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.
“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.
, 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.
“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.
FROM THE LANCET GASTROENTEROLOGY & HEPATOLOGY
Liquid Biopsy for Colorectal Cancer Appears Promising But Still Lacks Robust Efficacy
, 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.
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.
“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.
, 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.
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.
“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.
, 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.
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.
“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.
IBS Placebo Responses Predicted By Patient Beliefs, Relationship with Provider
, 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.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
Irritable bowel syndrome (IBS) is associated with impaired functioning and work or school absenteeism. Current treatments are suboptimal and there is a need for improved management strategies. A challenge in designing trials can be placebo response. Placebo can also be a treatment modality with approximately 40% response in adults and children with IBS. The study by Lackner et al. provides predictors of the magnitude, and timing of placebo response. Accordingly, certain behaviors and strategies adopted by patients and clinicians in addition to pharmacotherapy can harness greater clinical improvements.
While patient factors such as stress levels, somatization, and anxiety played a role in predicting rapid and delayed placebo response, an interesting domain was “cognitive reappraisal,” the ability to alter the impact of stressful events by reframing unpleasantness toward them. This was associated with greater global improvement post treatment and differed between rapid and delayed responders. Cognitive reappraisal has shown changes in the limbic system such as activation of the prefrontal cortex like placebo analgesia. Thus, optimal introduction of treatments to patients may be important to maximize the cognitive appraisal abilities, enhance expectation effects, and improve treatment outcomes. Similarly, minimizing nocebo effects may be equally important to decrease side effects.
The agreement between patients and clinicians on treatment goals and tasks also predicted response. Thus, developing thorough treatment goals beforehand could be crucial to sustain treatment responses. For example, improved functioning may be a goal to agree upon rather than symptom reduction alone before commencement of treatment. Similarly, shared decision-making during treatment may have a tremendous influence on favorable outcomes.
Neha Santucci, MD, MBBS, is director of the Disorders of Gut-Brain Interaction Program at the Neurogastroenterology and Motility Center, Pediatric Gastroenterology, Hepatology and Nutrition, Cincinnati Children’s Hospital Medical Center, and associate professor of pediatrics, University of Cincinnati College of Medicine.
, 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.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
, 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.
“This limitation partly reflects the demands of efficacy trials that prioritize pre- and posttreatment data over that collected during acute phase, when the putative mechanisms underpinning placebo effects play out,” the investigators wrote. “The expectation that one can benefit from a treatment, for example, is optimally assessed after its rationale is delivered but before a clinically thorough regimen is provided, meaning that it cannot be fruitfully assessed at baseline along with other personal characteristics when treatment rationale is not fully disclosed. The same applies to relational factors such as patient-physician interactions that define the context where treatment is delivered, and placebo response presumably incubates.”
To explore the above factors, Dr. Lackner and colleagues conducted a secondary analysis of 145 patients with Rome III-diagnosed IBS from the Irritable Bowel Syndrome Outcome Study.
During the study, patients were randomized to receive either 10 sessions of clinic-based cognitive behavioral therapy (CBT), 4 sessions of minimal-contact CBT, or 4 sessions of supportive counseling and education without any prescribed behavior changes. Responses were measured by the IBS version of the Clinical Global Improvement Scale, with evaluations conducted at the treatment midpoint and 2 weeks after treatment.
Candidate predictors at baseline included pain catastrophizing, somatization, emotion regulation, neuroticism, stress, and others, while clinical factors included treatment expectancy/credibility and patient-provider relationship.
Responses during treatment were significantly associated with lower somatization and stress level at baseline, as well as greater patient-provider agreement on treatment tasks (P less than .001).
Posttreatment responses were significantly associated with baseline gastroenterologist-rated IBS severity, anxiety, agreement that the patient and the provider shared goals from a provider perspective, and ability to reframe stressful events in a positive light (P less than .001). That ability to reconsider emotions was also associated with a faster placebo response (P = .011).
“The strength of placebo responsiveness is subject to the influence of patient factors that precede treatment delivery (rethinking or reinterpreting stressful situations in everyday life in a way that reduces their subsequent impact) and specific elements of provider-patient interactions that occur while treatment is delivered, particularly practitioners’ estimation that patients agree on their goals and tasks to achieve them,” Dr. Lackner and colleagues concluded. “We believe this line of research can help identify factors that drive placebo response and narrow the patient-provider ‘mismatch’ that undermines the quality, satisfaction, and efficiency of IBS care regardless of what treatment is delivered.”
The study was supported by the NIH. The investigators disclosed no conflicts of interest.
FROM GASTRO HEP ADVANCES
Study Characterizes Pathologic B-Cell Maturation in Crohn’s Disease
, 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.
“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.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
The pathophysiology of inflammatory bowel disease (IBD) is complex and involves multiple mechanisms. Among these mechanisms, dysfunction and overactivation of the intestinal immune system are widely implicated. Dysfunctions in both the innate and adaptive immune systems have been demonstrated. However, mucosal immunology research related to IBD has long been particularly focused on T lymphocytes due to the failure of the rituximab clinical trial (anti-CD20) in ulcerative colitis (UC). Recent data have indicated modifications in the landscape of B lymphocyte subpopulations within the inflamed mucosa of patients with UC or ileal Crohn’s disease (CD).
Similarly, to what was previously shown in the inflamed colonic and ileal mucosa of IBD patients, isotype usage showed a skewing from IgA to IgG1. Further analysis of the B cell receptor (BCR) showed a very diverse repertoire of B cells, reflecting a large panel of antigenic stimulation. As we know, IBD are complex diseases that may not be explained by a single or a limited set of antigenic drivers.
Whether these changes in the B-cell compartment are a triggering event of inflammation or a bystander, reflecting the increased intestinal permeability and exposure to microbiota antigens during inflammation, remains to be explored and further studied.
Mathieu Uzzan, MD, PhD, is based in the gastroenterology department, Hopital Henri Mondor, APHP, Créteil, France. He has no relevant disclosures.
, 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.
“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.
, 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.
“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.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
AGA Supports Fecal Microbiota Therapies for CDI but Not IBD or IBS
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.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
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.
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.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
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.
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.”
Designed to counteract intestinal dysbiosis and restore protective gut flora, the FMT approach includes conventional, colonoscopically delivered donor stool transplants as well as two newly approved options: rectally given fecal microbiota (live-jslm/ Rebyota) and most recently, orally delivered fecal microbiota spores (live-brpk/ Vowst).
The AGA urges careful pretreatment consideration for patients who require frequent antibiotics or long-term antibiotic prophylaxis since ongoing antibiotics may diminish the efficacy of FMT.
The guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis, followed by the Evidence-to-Decision framework to develop recommendations for these therapies and algorithms for their implementation into clinical practice.
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.
FROM GASTROENTEROLOGY
Global Meta-Analysis: 1 in 12 Adults May Have Fecal Incontinence
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
Fecal incontinence (FI) is the GI disease that remains invisible to many except its sufferers. Even in the seemingly safe confines of a physician’s office, many patients won’t admit to providers that they suffer from this socially isolating condition. This systematic review and meta-analysis by Mack et al. — like other prevalence studies before it — serves as a useful reminder just how common this hidden disease remains. While FI is common in institutionalized persons, this study importantly found that 1 in 12 community-dwelling individuals worldwide suffer from FI as well.
What should the practicing clinician take away from this study? Simply put, when it comes to FI, you need to ask: how often, how much, how urgent (or passive), and what type (solid or liquid). This disease is far too common to remain in the shadows, yet most GI fellows do not receive sufficient training on a condition that is so widespread.
Kyle Staller, MD, MPH, is director, GI Motility Laboratory at Massachusetts General Hospital and Harvard Medical School, both in Boston. He has served as a consultant for Anji, Ardelyx, GI Supply, Mahana, and Restalsis, and received research support from Ardelyx.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FI is more common among individuals 60 years and older, yet a considerable portion of younger people — almost 5% — may also suffer from FI, reported Isabelle Mack, PhD, of University Medical Hospital, Tübingen, Germany, and colleagues.
“Clinicians’ understanding of the prevalence and risk factors for FI have evolved with time,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Initially, FI was regarded as a symptom that predominantly affected older people, especially nursing home residents. Its prevalence among community-dwelling adults was underrecognized, possibly because persons with FI were hesitant to even disclose that they were symptomatic. Now, we recognize that FI is common in the community.”
The only previous meta-analysis of FI, published in 2006, included both community and noncommunity studies, and reported an FI prevalence of 4.3%. Two subsequent reviews put the median prevalence at 7.7%, yet neither offered geographic insights.
To address this knowledge gap, Dr. Mack and colleagues conducted a meta-analysis of 80 studies involving 548,316 community-dwelling teenagers and adults. The median response rate across the studies was 66%.
Evaluating these data revealed a pooled global prevalence of FI was 8.0%, with a lower rate of 5.4% when FI was confined to Rome criteria.
“Placed in perspective, the 8.0% prevalence of FI is lower than or similar to the global prevalence of IBS, as assessed by a meta-regression (11.2%) and by a systematic review (8.8%) using pre–Rome IV criteria, and it is twofold greater than the IBS prevalence assessed with Rome IV criteria,” the investigators wrote.
Among individuals aged 60 years and older, the FI prevalence was 9.3%, compared with 4.9% for younger people (odds ratio [OR], 1.75; 95% CI, 1.39-2.20).
“These differences are at least partly explained by age-associated declines in anorectal function (e.g., lower anal resting pressure and rectal distensibility, denervation of the external anal sphincter),” the investigators wrote.
FI was also significantly more common among women than men (9.1% vs 7.4%; OR, 1.17; 95% CI, 1.06-1.28).
“Although these differences in FI prevalence between men and women seem relatively small, most patients with FI who seek medical attention are women (unpublished data),” the investigators wrote. “We suspect that men less commonly seek medical attention for FI because they may be secretly resigned to having FI, because FI may have less of an emotional impact on men, and because health literacy with regard to FI is lower for men.”
Geographically, prevalence of FI was highest in Australia and Oceania, followed by North America, Asia, and Europe. Data were insufficient to estimates rates in the Middle East and Africa.
Dr. Mack and colleagues concluded by noting how bothersome FI is for so many individuals worldwide, which should warrant closer attention from the medical community.
“Because nearly one in four community-dwelling women with FI report that the symptom has a moderate or severe impact on one or more domains of quality of life, more resources should be devoted to research in this area,” they wrote. “Future epidemiologic studies of FI should also assess the severity of FI, risk factors for FI, and the impact of FI on quality of life. In addition, because some patients are reluctant to acknowledge or discuss FI during an in-person interview, written or internet-based surveys may be preferable.”
This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. The investigators disclosed no conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Offers Practical Advice on IBD Diets
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
FROM GASTROENTEROLOGY
AGA Outlines a Plan to Improve the Care of All Patients with lBD
A new AGA white paper, published in Clinical Gastroenterology and Hepatology, highlights barriers to care and calls for collaboration among our healthcare community, insurers, pharmaceutical companies, and legislators to improve and optimize care for more than 3 million Americans living with inflammatory bowel disease (IBD).
Over the last two decades, there has been a revolution in therapeutics fueled by exciting research and development that continues to expand the treatment options for IBD, offering tools for better disease control. However, the most effective therapies are cost prohibitive and have largely become inaccessible due to insurer-mandated barriers to care, such as prior authorization and step therapy.
AGA has created a plan that addresses these barriers and proposes tangible solutions to provide patients with high quality, high value care.
1. The lived experiences and valuable insights from both patients and expert clinicians should be reflected in the data and research represented in the field.
2. AGA recognizes the powerful benefit of individually tailoring IBD therapy based on risk, comorbidities and response, and encourages all stakeholders to do the same.
3. As a field, we need to move beyond insurer-mandated step therapy and fail first policies.
4. AGA urges insurers to cover all necessary disease activity and drug level monitoring, which will ensure patients are able to achieve treat-to-target-driven outcomes.
5. Streamlined and expedited expert reviews should be guaranteed to all providers when they are mandated by an insurer.
6. To ensure transparency and accountability, AGA wants to require that payors publish their denial and appeals data.
7. AGA believes that holistic patient-centered multidisciplinary care, including psychosocial and dietary support, should be covered by insurance. Having access to such care contributes to improved patient resilience and well-being, which will lead to decreased health care utilization and better health outcomes.
8. AGA supports the creation and continuation of a variety of patient education programs to improve health literacy and awareness of complex health care systems.
9. AGA is committed to improving patients’ access to expert specialized clinical IBD care. This includes flexible delivery models to ensure that underserved populations are being reached. In addition, AGA supports training and educating specialty providers across the spectrum of medical care (advanced practice providers, nurse educators, etc.) to increase the number of qualified IBD providers.
10. Piloting innovative shared incentive partnerships between high value subspecialty care practices and payors will be a new shared goal.
11. AGA wants to engage pharmaceutical partners in developing equitable programs to address prohibitive drug costs while also expanding patient access and support.
12. AGA plans to continue to advocate for legislation to make access to therapy equitable for Medicare and Medicaid patients.
“Unaffordable drug costs, step therapy, and other insurer-mandated barriers are fixable problems,” said M. Anthony Sofia, MD, a coauthor of the AGA white paper and an IBD specialist at Oregon Health and Science University, Portland.
“Every day, we see people that have been harmed by delayed and inadequate care. Solving these barriers would lift an unimaginable weight off our patient’s shoulders and allow them to lead healthier lives. We must work together to collaborate on solutions to strengthen and advance the care for all people with IBD.”
View the full white paper here.
A new AGA white paper, published in Clinical Gastroenterology and Hepatology, highlights barriers to care and calls for collaboration among our healthcare community, insurers, pharmaceutical companies, and legislators to improve and optimize care for more than 3 million Americans living with inflammatory bowel disease (IBD).
Over the last two decades, there has been a revolution in therapeutics fueled by exciting research and development that continues to expand the treatment options for IBD, offering tools for better disease control. However, the most effective therapies are cost prohibitive and have largely become inaccessible due to insurer-mandated barriers to care, such as prior authorization and step therapy.
AGA has created a plan that addresses these barriers and proposes tangible solutions to provide patients with high quality, high value care.
1. The lived experiences and valuable insights from both patients and expert clinicians should be reflected in the data and research represented in the field.
2. AGA recognizes the powerful benefit of individually tailoring IBD therapy based on risk, comorbidities and response, and encourages all stakeholders to do the same.
3. As a field, we need to move beyond insurer-mandated step therapy and fail first policies.
4. AGA urges insurers to cover all necessary disease activity and drug level monitoring, which will ensure patients are able to achieve treat-to-target-driven outcomes.
5. Streamlined and expedited expert reviews should be guaranteed to all providers when they are mandated by an insurer.
6. To ensure transparency and accountability, AGA wants to require that payors publish their denial and appeals data.
7. AGA believes that holistic patient-centered multidisciplinary care, including psychosocial and dietary support, should be covered by insurance. Having access to such care contributes to improved patient resilience and well-being, which will lead to decreased health care utilization and better health outcomes.
8. AGA supports the creation and continuation of a variety of patient education programs to improve health literacy and awareness of complex health care systems.
9. AGA is committed to improving patients’ access to expert specialized clinical IBD care. This includes flexible delivery models to ensure that underserved populations are being reached. In addition, AGA supports training and educating specialty providers across the spectrum of medical care (advanced practice providers, nurse educators, etc.) to increase the number of qualified IBD providers.
10. Piloting innovative shared incentive partnerships between high value subspecialty care practices and payors will be a new shared goal.
11. AGA wants to engage pharmaceutical partners in developing equitable programs to address prohibitive drug costs while also expanding patient access and support.
12. AGA plans to continue to advocate for legislation to make access to therapy equitable for Medicare and Medicaid patients.
“Unaffordable drug costs, step therapy, and other insurer-mandated barriers are fixable problems,” said M. Anthony Sofia, MD, a coauthor of the AGA white paper and an IBD specialist at Oregon Health and Science University, Portland.
“Every day, we see people that have been harmed by delayed and inadequate care. Solving these barriers would lift an unimaginable weight off our patient’s shoulders and allow them to lead healthier lives. We must work together to collaborate on solutions to strengthen and advance the care for all people with IBD.”
View the full white paper here.
A new AGA white paper, published in Clinical Gastroenterology and Hepatology, highlights barriers to care and calls for collaboration among our healthcare community, insurers, pharmaceutical companies, and legislators to improve and optimize care for more than 3 million Americans living with inflammatory bowel disease (IBD).
Over the last two decades, there has been a revolution in therapeutics fueled by exciting research and development that continues to expand the treatment options for IBD, offering tools for better disease control. However, the most effective therapies are cost prohibitive and have largely become inaccessible due to insurer-mandated barriers to care, such as prior authorization and step therapy.
AGA has created a plan that addresses these barriers and proposes tangible solutions to provide patients with high quality, high value care.
1. The lived experiences and valuable insights from both patients and expert clinicians should be reflected in the data and research represented in the field.
2. AGA recognizes the powerful benefit of individually tailoring IBD therapy based on risk, comorbidities and response, and encourages all stakeholders to do the same.
3. As a field, we need to move beyond insurer-mandated step therapy and fail first policies.
4. AGA urges insurers to cover all necessary disease activity and drug level monitoring, which will ensure patients are able to achieve treat-to-target-driven outcomes.
5. Streamlined and expedited expert reviews should be guaranteed to all providers when they are mandated by an insurer.
6. To ensure transparency and accountability, AGA wants to require that payors publish their denial and appeals data.
7. AGA believes that holistic patient-centered multidisciplinary care, including psychosocial and dietary support, should be covered by insurance. Having access to such care contributes to improved patient resilience and well-being, which will lead to decreased health care utilization and better health outcomes.
8. AGA supports the creation and continuation of a variety of patient education programs to improve health literacy and awareness of complex health care systems.
9. AGA is committed to improving patients’ access to expert specialized clinical IBD care. This includes flexible delivery models to ensure that underserved populations are being reached. In addition, AGA supports training and educating specialty providers across the spectrum of medical care (advanced practice providers, nurse educators, etc.) to increase the number of qualified IBD providers.
10. Piloting innovative shared incentive partnerships between high value subspecialty care practices and payors will be a new shared goal.
11. AGA wants to engage pharmaceutical partners in developing equitable programs to address prohibitive drug costs while also expanding patient access and support.
12. AGA plans to continue to advocate for legislation to make access to therapy equitable for Medicare and Medicaid patients.
“Unaffordable drug costs, step therapy, and other insurer-mandated barriers are fixable problems,” said M. Anthony Sofia, MD, a coauthor of the AGA white paper and an IBD specialist at Oregon Health and Science University, Portland.
“Every day, we see people that have been harmed by delayed and inadequate care. Solving these barriers would lift an unimaginable weight off our patient’s shoulders and allow them to lead healthier lives. We must work together to collaborate on solutions to strengthen and advance the care for all people with IBD.”
View the full white paper here.
AI-Identified Vascular Healing Can Predict Clinical Relapse in Ulcerative Colitis
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
STOCKHOLM — , according to data from the study of a novel investigational tool.
Clinical relapse was predicted in 3% of patients identified as having vascular healing in all segments compared with 23.9% in those with vascular activity (ie, one or more segments were active), reported Yasuharu Maeda, MD, gastroenterologist from Showa University Northern Yokohama Hospital, Digestive Disease Center, Yokohama, Japan.
In patients with a Mayo Endoscopic Score (MES) ≤ 1, the clinical relapse rate was 3% and 18.6% in the vascular healing and vascular active groups, respectively, he said.
Endoscopic remission is a crucial treat-to-target goal in patients with UC, and image-enhanced endoscopy is spreading in routine practice as a way to detect inflammation and to predict outcomes, Dr. Maeda said.
“Image-enhanced vascular findings lead to a stronger correlation with histological activities and long-term prognosis compared with white light endoscopy assessment,” he explained. “It also means that assessment can be done on-site without biopsy, pathologist effort, and associated costs; however, specialist training is required to achieve a high accuracy in outputs.”
Dr. Maeda presented the data (Abstract OP16) at the annual congress of the European Crohn’s and Colitis Organisation.
Stratifying the Relapse Risk
Dr. Maeda and colleagues developed a novel AI-based narrow-band imaging system, training it by using 8853 images from 167 patients with UC.
The AI system, EndoBRAIN-UC (Cybernet System Corp, Tokyo), is in use and currently adapted for only one endoscope, the Endocyto CFH290EC (Olympus EMEA, Tokyo), but for the purpose of this study, it was trained on images from five different scopes.
“By combining narrow-band imaging and AI, we developed a system where we can differentiate between vascular activity and vascular healing. This allows us to predict relapse,” Dr. Maeda said.
In an open-label, prospective cohort study, they tested the system with the aim of assessing the efficacy of AI-identified vascular healing to stratify the relapse risk in 100 patients showing clinical remission of UC (ie, partial MES ≤ 1).
Patient characteristics were similar between both groups with an average disease duration of 10 years.
In the vascular healing group (n = 33), the average age was 52 years, 20% were men, 58% had extensive colitis, and 52% had a MES score of 0.
In the vascular active group (n = 67), the average age was 56 years, 32% were men, 61% had extensive colitis, and 25% had a MES score of 0.
Colonoscopy was performed using the AI system to identify mucosa as healing or active for six colorectal segments of each patient. The MES and histologic assessment for these segments were also recorded. Patients were then followed for up to 12 months and assessed for clinical relapse.
The clinical relapse rate was higher in the vascular active group than in the vascular healing group as identified by AI.
“We only evaluated the diagnostic output of the AI but obtained white light endoscopies and biopsies for contrast studies,” Dr. Maeda noted.
They also looked at whether the endoscopist’s level of experience (ie, trainee or expert) was important but found that clinical relapse predictive values were independent of the endoscopist’s experience.
Still in the Early Stages
AI-assisted colonoscopy work is still at an early stage , said session co-moderator, Monika Ferlitsch, MD, head of Internal Medicine Department II, gastroenterology and hepatology, Evangelical Hospital, in Vienna, Austria.
We now have initial results, but “I suspect it will take 10-20 years for implementation into routine clinical practice,” she said.
The best outcome for our patients is to be able to predict response to therapy and recurrence rates, “and we see this is possible now with AI. But of course, we need more clinical data to support it,” Dr. Ferlitsch said.
Dr. Maeda and Dr. Ferlitsch have declared no financial disclosures.
A version of this article appeared on Medscape.com.
FROM ECCO 2024