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Colorectal Cancer Screening Choices: Is Compliance Key?
SAN DIEGO — , and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.
Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week® (DDW) 2025.
“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).
A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.
He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.
With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.
Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.
Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.
“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.
Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).
“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.
Blood-Based Tests: Caveats, Harms?
Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.
While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.
Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.
These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”
Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.
Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.
He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.
“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.
In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.
Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.
Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.
The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”
“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”
What About FIT?
Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.
Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.
In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.
Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).
“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.
Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.
“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.
Colonoscopy: ‘Best for First-Line Screening’
Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.
A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.
In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.
Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.
“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.
Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.
The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.
Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.
Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.
A version of this article appeared on Medscape.com.
SAN DIEGO — , and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.
Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week® (DDW) 2025.
“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).
A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.
He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.
With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.
Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.
Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.
“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.
Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).
“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.
Blood-Based Tests: Caveats, Harms?
Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.
While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.
Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.
These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”
Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.
Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.
He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.
“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.
In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.
Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.
Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.
The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”
“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”
What About FIT?
Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.
Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.
In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.
Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).
“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.
Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.
“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.
Colonoscopy: ‘Best for First-Line Screening’
Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.
A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.
In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.
Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.
“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.
Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.
The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.
Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.
Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.
A version of this article appeared on Medscape.com.
SAN DIEGO — , and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical.
Regarding tests, “perfect is not possible,” said William M. Grady, MD, AGAF, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week® (DDW) 2025.
“We have to remember that that’s the reality of colorectal cancer screening, and we need to meet our patients where they live,” said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome).
A big point in their favor is their convenience and higher patient compliance — better tests that don’t get done do not work, he stressed.
He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years.
With troubling increases in CRC incidence among younger patients, “that’s a group we’re particularly concerned about,” Grady said.
Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted.
Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy.
“What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,” he said.
Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%).
“The bottom line is that these tests decrease CRC mortality and incidence, and we know there’s a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,” Grady said.
Blood-Based Tests: Caveats, Harms?
Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, in Pittsburgh, Pennsylvania, checked off some of the key caveats.
While the overall sensitivity of blood-based tests may look favorable, these tests don’t detect early CRC well,” said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome.
Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported.
These rates are “similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,” Schoen said. “Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].”
Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted.
Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen.
He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%.
“We have a long way to go to make sure that people who get positive noninvasive tests get followed up,” he said.
In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities.
Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%.
Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, “the rate of CRC deaths would increase,” Schoen noted.
The findings underscore that “blood testing is unfavorable as a ‘substitution test,’” he added. “In fact, widespread adoption of blood testing could increase CRC morbidity.”
“Is it better than nothing?” he asked. “Yes, but only if performance of a colonoscopy after a positive test is accomplished.”
What About FIT?
Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk.
Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%.
In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively.
Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively).
“This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,” Tinmouth said.
Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy.
“FIT has clear and compelling advantages over colonoscopy,” she said. As well as better compliance among all groups, “it is less costly and also better for the environment [by using fewer resources],” she added.
Colonoscopy: ‘Best for First-Line Screening’
Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal.
A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added.
In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy.
Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said.
“Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,” she said.
Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study’s appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality.
The collective findings underscore that “colonoscopy as a standalone test is uniquely cost-effective,” in the face of costs related to colon cancer treatment.
Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.
Grady had been on the scientific advisory boards for Guardant Health and Freenome and had consulted for Karius. Shoen reported relationships with Guardant Health and grant/research support from Exact Sciences, Freenome, and Immunovia. Tinmouth had no disclosures to report. Patel disclosed relationships with Olympus America and Exact Sciences.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Barrett’s Esophagus: No Survival Difference Between Regular and At-Need Surveillance
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
SAN DIEGO—Gastroenterologists have debated the best course of action for patients with Barrett’s esophagus for decades. Which is better for detecting early malignancy and preventing progression to esophageal adenocarcinoma (EAC) — surveillance endoscopy at regular intervals or only when symptoms occur? Does one offer a better chance of survival than the other?
Now, researchers who conducted what they believe is the first randomized clinical trial comparing the two approaches say they have the answer.
, said Oliver Old, MD, a consultant upper-GI surgeon at Gloucestershire Royal Hospital, England, who presented the findings at Digestive Disease Week® (DDW) 2025.
At-need endoscopy may be a safe alternative for low-risk patients, the research team concluded.
The BOSS Trial
The Barrett’s Oesophagus Surveillance Versus Endoscopy At Need Study (BOSS) ran from 2009 to 2024 at 109 centers in the UK, and 3452 patients with Barrett’s esophagus of 1 cm circumferential or a 2 cm noncircumferential tongue or island were followed for a minimum of 10 years.
Researchers randomly assigned patients to undergo upper gastrointestinal endoscopy with biopsy every 2 years (the standard of care when the trial was set up) or endoscopy “at-need” when symptoms developed. Patients in the latter group were counseled about risk and were offered endoscopy for a range of alarm symptoms.
The study found no statistically significant difference in all-cause mortality risk between the two groups. Over the study period, 333 of 1733 patients (19.2%) in the surveillance group died, as did 356 of 1719 patients (20.7%) in the at-need group.
Similarly, no statistically significant between-group difference was found in the risk for cancer-specific mortality. About 6.2% of patients died from cancer in both groups — 108 in the regular surveillance group and 106 in the at-need group.
Nor was there a statistically significant difference in diagnosis of EAC, with 40 regular surveillance patients (2.3%) and 31 at-need patients (1.8%) receiving the diagnosis over median follow-up of 12.8 years. Cancer stage at diagnosis did not differ significantly between groups.
“The really low rate of progression to esophageal adenocarcinoma” was a key finding, Old said. The rate of progression to EAC was 0.23% per patient per year, he said.
Low- or high-grade dysplasia was detected in 10% of patients in the regular surveillance group, compared with 4% in the at-need group.
The mean interval between endoscopies was 22.9 months for the regular surveillance group and 31.5 months for the at-need group, and the median interval was 24.8 months and 25.7 months, respectively. The mean number of endoscopies was 3.5 in the regular surveillance group and 1.4 in the at-need group.
Eight patients in the regular surveillance group (0.46%) and seven in the at-need group (0.41%) reported serious adverse events.
Will BOSS Change Minds?
Current surveillance practices “are based on pure observational data, and the question of whether surveillance EGD [esophagogastroduodenoscopy] impacts EAC diagnosis and mortality has been ongoing,” said Margaret Zhou, MD, MS, clinical assistant professor at Stanford University School of Medicine, Stanford, California. A randomized clinical trial on the subject has been needed for years, she added.
However, Zhou said, “In my opinion, this study does not end the debate and will not change my practice of doing surveillance endoscopy on NDBE [nondysplastic Barrett’s esophagus], which I typically perform every 3-5 years, based on current guidelines.”
The American Gastroenterological Association clinical practice guideline, issued in June 2024, addresses surveillance and focuses on a patient-centered approach when deciding on treatment or surveillance.
Patients in the at-need endoscopy arm underwent endoscopy almost as frequently as the patients randomly assigned to regular surveillance, at a median interval of about 2 years, Zhou noted. Therefore, she said, “It’s difficult to conclude from this study that surveillance endoscopy has no impact.”
Additionally, the study was underpowered to detect a difference in all-cause mortality and assumed a progression rate for nondysplastic Barrett’s esophagus that is higher than the current understanding, Zhou said. “It also did not address the important question of EAC-related mortality, which would be an important outcome to be able to assess whether surveillance EGD has an impact,” she said.
Joel H. Rubenstein, MD, MSc, AGAF, director of the Barrett’s Esophagus Program and professor in the Division of Gastroenterology at the University of Michigan Medical School, Ann Arbor, agreed that the study doesn’t answer the pressing question of whether surveillance works.
While Rubenstein said he would not tell colleagues or patients to stop routine surveillance in patients with Barrett’s esophagus on the basis of these results, “it is a reminder that we should be circumspect in who we label as having Barrett’s esophagus, and we should be more proactive in discussing discontinuation of surveillance in patients based on advancing age and comorbidities.”
The study was funded by the UK’s National Institute for Health and Care Research. Zhou is a consultant for CapsoVision and Neptune Medical. Rubenstein has received research funding from Lucid Diagnostics. Old reported no disclosures.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Post-Polypectomy Colorectal Cancers Common Before Follow-Up
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to new research.
Of key factors linked to a higher risk for such cases, one stands out — the quality of the baseline colonoscopy procedure.
“A lot of the neoplasia that we see after polypectomy was probably either missed or incompletely resected at baseline,” said Samir Gupta, MD, AGAF, a professor of medicine in the Division of Gastroenterology, UC San Diego Health, La Jolla, California, in discussing the topic at Digestive Diseases Week® (DDW) 2025.
“Therefore, what is key to emphasize is that [colonoscopy] quality is probably the most important factor in post-polypectomy risk,” he said. “But, advantageously, it’s also the most modifiable factor.”
Research shows that the risk for CRC incidence following a colonoscopy ranges from just about 3.4 to 5 cases per 10,000 person-years when baseline findings show no adenoma or a low risk; however, higher rates ranging from 13.8 to 20.9 cases per 10,000 person-years are observed for high-risk adenomas or serrated polyps, Gupta reported.
“Compared with those who have normal colonoscopy, the risk [for CRC] with high-risk adenomas is increased by nearly threefold,” Gupta said.
In a recent study of US veterans who underwent a colonoscopy with polypectomy between 1999 and 2016 that was labeled negative for cancer, Gupta and his colleagues found that over a median follow-up of 3.9 years, as many as 55% of 396 CRCs that occurred post-polypectomy were detected prior to the recommended surveillance colonoscopy.
The study also showed that 40% of post-polypectomy CRC deaths occurred prior to the recommended surveillance exam over a median follow-up of 4.2 years.
Cancers detected prior to the recommended surveillance exam were more likely to be diagnosed as stage IV compared with those diagnosed later (16% prior to recommended surveillance vs 2.1% and 8.3% during and after, respectively; P = .003).
Importantly, the most prominent reason for the cancers emerging in the interval before follow-up surveillance was missed lesions during the baseline colonoscopy (60%), Gupta said.
Colonoscopist Skill and Benchmarks
A larger study of 173,288 colonoscopies further underscores colonoscopist skill as a key factor in post-polypectomy CRC, showing that colonoscopists with low vs high performance quality — defined as an adenoma detection rate (ADR) of either < 20% vs ≥ 20% — had higher 10-year cumulative rates of CRC incidence among patients following a negative colonoscopy (P < .001).
Likewise, in another analysis of low-risk vs high-risk polyps, a higher colonoscopist performance status was significantly associated with lower rates of CRCs (P < .001).
“Higher colonoscopist performance was associated with a lower cumulative colorectal cancer risk within each [polyp risk] group, such that the cumulative risk after high-risk adenoma removal by a higher performing colonoscopist is similar to that in patients who had a low-risk adenoma removed by a lower performer,” Gupta explained.
“So, this has nothing to do with the type of polyp that was removed — it really has to do with the quality of the colonoscopist,” he said.
The American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy Quality Task Force recently updated recommended benchmarks for colonoscopists for detecting polyps, said Aasma Shaukat, MD, AGAF, director of GI Outcomes Research at NYU Grossman School of Medicine, New York City, in further discussing the issue in the session.
They recommend an ADR of 35% overall, with the recommended benchmark being ≥ 40% for men aged 45 years or older and ≥ 30% for women aged 45 years or older, with a rate of 50% for patients aged 45 years or older with an abnormal stool test, Shaukat explained.
And “these are minimum benchmarks,” she said. “Multiple studies suggest that, in fact, the reported rates are much higher.”
Among key strategies for detecting elusive adenomas is the need to slow down withdrawal time during the colonoscopy in order to take as close a look as possible, Shaukat emphasized.
She noted research that her team has published showing that physicians’ shorter withdrawal times were in fact inversely associated with an increased risk for cancers occurring prior to the recommended surveillance (P < .0001).
“Multiple studies have shown it isn’t just the time but the technique with withdrawal,” she added, underscoring the need to flatten as much of the mucosa and folds as possible during the withdrawal. “It’s important to perfect our technique.”
Sessile serrated lesions, with often subtle and indistinct borders, can be among the most difficult polyps to remove, Shaukat noted. Studies have shown that as many as 31% of sessile serrated lesions are incompletely resected, compared with about 7% of tubular adenomas.
Patient Compliance Can’t Be Counted On
In addition to physician-related factors, patients themselves can also play a role in post-polypectomy cancer risk — specifically in not complying with surveillance recommendations, with reasons ranging from cost to the invasiveness and burden of undergoing a surveillance colonoscopy.
“Colonoscopies are expensive, and participation is suboptimal,” Gupta said.
One study of high-risk patients with adenoma shows that only 64% received surveillance, and many who did receive surveillance received it late, he noted.
This underscores the need for better prevention as well as follow-up strategies, he added.
Recommendations for surveillance exams from the World Endoscopy Organization range from every 3 to 10 years for patients with polyps, depending on the number, size, and type of polyps, to every 10 years for those with normal colonoscopies and no polyps.
A key potential solution to improve patient monitoring within those periods is the use of fecal immunochemical tests (FITs), which are noninvasive, substantially less burdensome alternatives to colonoscopies, which check for blood in the stool, Gupta said.
While the tests can’t replace the gold standard of colonoscopies, the tests nevertheless can play an important role in monitoring patients, he said.
Evidence supporting their benefits includes a recent important study of 2226 patients who underwent either post-polypectomy colonoscopy, FIT (either with FOB Gold or OC-Sensor), or FIT-fecal DNA (Cologuard) test, he noted.
The results showed that the OC-Sensor FIT had a 71% sensitivity, and FIT-fecal DNA had a sensitivity of 86% in the detection of CRC.
Importantly, the study found that a positive FIT result prior to the recommended surveillance colonoscopy reduced the time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20 months, respectively.
FIT Tests Potentially a ‘Major Advantage’
“The predictive models and these noninvasive tests are likely better than current guidelines for predicting who has metachronous advanced neoplasia or colon cancer,” Gupta said.
“For this reason, I really think that these alternatives have a potentially major advantage in reducing colonoscopy burdens. These alternatives are worthwhile of studying, and we really do need to consider them,” he said.
More broadly, the collective evidence points to factors that can and should be addressed with a proactive diligence, Gupta noted.
“We need to be able to shift from using guidelines that are just based on the number, size, and histology of polyps to a scenario where we’re doing very high-quality colonoscopies with excellent ADR rates and complete polyp excision,” Gupta said.
Furthermore, “the use of tools for more precise risk stratification could result in a big, low-risk group that could just require 10-year colonoscopy surveillance or maybe even periodic noninvasive surveillance, and a much smaller high-risk group that we could really focus our attention on, doing surveillance colonoscopy every 3-5 years or maybe even intense noninvasive surveillance.”
Gupta’s disclosures included relationships with Guardant Health, Universal DX, CellMax, and Geneoscopy. Shaukat’s disclosures included relationships with Iterative Health and Freenome.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Train Advanced Practice Providers in Transnasal Endoscopy?
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
SAN DIEGO – , a pilot study showed.
“Our study showed that TNE can be performed safely by APPs, is well tolerated by patients, and significantly impacted patient management,” Whitney Kucher, PA-C, with Northwestern Medicine, Chicago, told GI & Hepatology News.
“The chief benefit of having APPs perform TNEs is increasing patient access and expediting management of upper GI [gastrointestinal] symptoms in patients,” said Kucher who presented the study at Digestive Disease Week® (DDW) 2025.
The EvoEndo single-use endoscopy system received 510(k) clearance from the US Food and Drug Administration in early 2022.
The system includes a sterile, single-use, flexible gastroscope designed for unsedated transnasal upper endoscopy and a small portable video controller.
Unsedated TNE can be used to evaluate and diagnose a wide range of upper GI conditions that may require frequent monitoring, including eosinophilic esophagitis (EoE), dysphagia, celiac disease, gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), malabsorption, and abdominal pain.
Kucher and colleagues assessed the ability for APPs to use the EvoEndo system to perform safe and accurate esophageal assessment using in-office TNE, following training.
TNE training lasted about 4 weeks and consisted of a stepwise approach involving lectures, simulation-based training, and hands-on supervised TNEs (10 per APP).
Once training was completed, and after providing consent, 25 patients were enrolled to undergo supervised TNE by an APP. Their mean age was 55 years, and 58% were women.
Indications for TNE were uncontrolled GERD symptoms in 12 patients, history of EoE in six patients, high-risk screening for BE in five patients, and dysphagia in two patients.
Technical success was achieved in all but one patient (96%), and there were no adverse events.
All 25 patients completed the procedure, with 17 (72%) giving it a TNEase score of 1 (with ease/no discomfort) or 2 (mild/occasional discomfort). Only two patients reported a score of 4 (very uncomfortable) but still completed the exam.
The average TNE procedure time was 7.3 minutes.
TNE findings changed management in 23 of 25 (92%) patients. The test led to a change in proton pump inhibitor dosing or interval in 14 patients (56%). Esophagogastroduodenoscopy (EGD) interval was extended in five patients (20%) and scheduled sooner in three patients (12%). Two patients (8%) had no change in management.
The study team said more data are needed in terms of learning curves, competency metrics, and health economics before widespread adoption can be supported.
“We are working on developing a standardized training plan so we can train more GI APPs in our department. We have plans to start an APP-driven TNE program in the coming months,” Kucher told GI & Hepatology News.
Caveats and Cautionary Notes
Commenting on this study for GI & Hepatology News, Amitabh Chak, MD, professor of medicine and oncology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, both in Cleveland, noted that the results are “similar to older studies where TNE appeared quite promising and APPs could be trained. There have been previous studies that APPs can perform colonoscopies and EGDs.”
Chak cautioned that previous studies showed that it took at least 50 supervised examinations for APPs to achieve the needed skills.
“Intubation transnasally can be painful for patients if not done with skill. Cognitive skills take longer. The gastroesophageal junction is dynamic, and recognition of subtle pathology takes training,” Chak noted.
“TNE has been around at least two decades. The challenge with uptake of TNE for Barrett’s screening has been acceptance by primary care physicians, patients and payers,” Chak told GI & Hepatology News.
The study had no specific funding. Kucher reported having no relevant disclosures. Chak reported having relationships with US Endoscopy, Lucid Diagnostics, Steris Endoscopy/US Endoscopy, Microtek, and Interpace Diagnostics.
A version of this article appeared on Medscape.com.
Precision-Medicine Approach Improves IBD Infliximab Outcomes
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
SAN DIEGO — In tough-to-treat chronic inflammatory bowel disease (IBD), a precision-medicine strategy based on patients’ molecular profiles showed efficacy in guiding anti–tumor necrosis factor (TNF) therapy treatment decisions to improve outcomes.
“,” said first author Florian Tran, MD, in presenting the late-breaking study at Digestive Disease Week (DDW) 2025.
“We have now been able to demonstrate for the first time that precision medicine can be successfully applied in the context of chronic inflammatory bowel diseases, leading to improved long-term outcomes,” said Tran, a professor of pathophysiology of chronic inflammation at the Institute of Clinical Molecular Biology and department of internal medicine, Kiel University and University Hospital Schleswig Holstein, Kiel, Germany.
Anti-TNF therapies can be highly effective in a range of immune-mediated inflammatory diseases, including IBD, but not all patients respond. Key singular candidates of biomarkers that could better predict a response show relatively low predictive power or a failure to replicate in independent studies.
In previous research, Tran and colleagues reported identification of early dynamic molecular changes in the blood that are more robustly predictive of responses to anti-TNF therapy.
“We have generated compelling evidence that therapy-induced changes in inflammatory pathways can reliably predict patient outcomes,” he said.
Among them are dynamic transcriptome changes that emerge early during treatment and can predict response to anti-TNF therapy, as well as clinical response trajectories that differ based on subgroups.
To further investigate the benefits of the multi-biomarker signatures collectively, as opposed to single biomarker–based algorithms, Tran and colleagues conducted the phase 3, open-label GUIDE-IBD trial, enrolling 102 adults with a confirmed diagnosis of Crohn’s disease (CD) or ulcerative colitis (UC) at three German university hospitals between February 2021 and January 2024.
All patients had been assigned the anti-TNF drug infliximab for the first time.
Study participants were randomized to receive either the molecular-guided care or standard medical care, with stratifications based on diagnosis, recruiting center, and baseline corticosteroid use.
Those in the molecular group received real-time molecular assessments at baseline and weeks 2, 6, 14, and 26, which included peripheral blood samples and biopsies of known messenger ribonucleic acid–based biomarkers.
The assessments also looked at infliximab and anti-drug antibody levels.
Molecular reports were then provided through molecular medicine boards for patients in the molecular-guidance group at weeks 2, 14, 26, and 52, whereas data from the standard-care group was not communicated.
Based on the biomarker data, therapy decisions were made such as adjustments to dosing, intervals, comedication, and switches in therapy.
The primary endpoint was the combined end point of disease control, defined as clinical remission (CD Activity Index < 150, partial Mayo score < 2), endoscopic remission (simplified endoscopic score for CD ≤ 4 [≤ 2 for isolated ileal disease], endoscopic Mayo score ≤ 1), or biochemical remission (C-reactive protein < 5 mg/L, fecal calprotectin < 250 mg/g).
A total of 87 patients completed the study with available primary endpoint data to week 52; there were 38 in the molecular care group and 49 in the standard care group. In each group, approximately half of the patients had CD and half had UC.
For the primary endpoint, comprehensive disease control was significantly more frequent in the molecular care group at week 52 (55.3%) than in the standard-care group (26.5%), with an absolute difference of 29% (P = .0072).
Furthermore, the secondary endpoint of the combined rate of endoscopic and clinical remission at week 52 was also higher in the molecular group (60.5%) than in the standard-care group (32.7%; P = .0163).
An exploratory analysis further showed therapy switches were more common in the molecular group (47%) than in the standard-care group (29%), with an increased rate of drug switching between 14 weeks and 26 weeks.
More patients in the molecular guidance group achieved comprehensive disease control (deep remission) at week 52 (P = .0135).
“The [molecular guidance] group was more likely to switch therapies after the induction period, reducing the number of patients who are suboptimally treated under infliximab,” Tran noted.
The results underscore that “even in the absence of a single ‘magic’ biomarker, precision medicine can materially improve patient outcomes by integrating complex molecular data into everyday clinical decisions, enabling more effective therapy choices and reducing unnecessary drug side effects,” he said.
Approach Pioneered in Oncology
Tran noted that the collaboration necessary for the approach was based on strategies pioneered in cancer centers, which have resulted in significant improvements in cancer therapy outcomes.
“For the first time in IBD, we have now integrated multidimensional molecular data and innovative drug-dosing models into these inflammation boards,” he said.
Key components of the intervention include a highly structured patient care process with fixed assessment timepoints, as well as “a multidisciplinary, quality-controlled decision-making process that is meticulously documented,” he explained.
The results underscore that “we must move away from sole physician–driven treatment decisions in IBD toward a structured expert-board model for therapy decision-making.”
Benefits in Other IBD Therapies Unclear
Commenting on the study, Ashwin N. Ananthakrishnan, MBBS, MPH, AGAF, an associate professor of medicine with Massachusetts General Hospital, Boston, noted that “this approach may help optimize existing treatment early and ensure that ineffective treatments don’t get dragged on.”
Importantly, however, a key limitation is that “this does not tell you upfront whether a treatment is likely to work or what the best treatment is,” Ananthakrishnan said in an interview. “That is a critically important unmet need in IBD.”
While doses are escalated, if needed, with infliximab and other biologic drugs, that may not be the case with other therapies, he explained.
“For other agents, such as JAK [Janus kinase] inhibitors, we actually start at a higher dose and then reduce for maintenance,” said Ananthakrishnan.
How this approach would work for these drugs or “for drugs where blood levels are not reflective of efficacy is also not clear,” he said.
Tran’s disclosures included relationships with AbbVie, Bristol-Myers-Squibb, CED Service, Celltrion Healthcare, Eli Lilly, Ferring Pharmaceutical, Janssen, Johnson & Johnson, Takeda, LEK Consulting, and Sanofi/Regeneron. Ananthakrishnan had no disclosures to report.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Once-Monthly Efimosfermin Leads to Significant MASH Improvement in Phase 2 Trial
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
SAN DIEGO — , according to results of a phase 2 trial presented at Digestive Disease Week (DDW) 2025.
An analogue of the fibroblast growth factor 21 (FGF21) protein, the agent regulates metabolic processes to reduce liver fat. It has a half-life of about 21 days, said study presenter Margaret J. Koziel, MD, chief medical officer at Boston Pharmaceuticals.
MASH is marked by inflammation and fibrosis and can progress to cirrhosis and liver failure. About 2%-5% of US adults have MASH, according to the American College of Gastroenterology. Up to 20% of adults who are obese may have the condition.
The researchers randomly assigned 84 participants with biopsy-confirmed F2/F3 MASH to receive once-monthly injections of 300 mg efimosfermin alpha (43 patients) or placebo (41 patients) for 24 weeks.
The mean body mass index (BMI) of participants in both groups was about 37. Most study sites were in the southern United States, so that BMI “reflects the demographics,” Koziel said. Mean age was 55 years in the placebo group and 53 years in the treatment group, and about half of patients in both groups were women. Eighteen patients in each group had a fibrosis stage of F3.
Primary endpoints were safety and tolerability.
Exploratory objectives included the proportion of patients achieving fibrosis improvement of one or more stages without MASH worsening, MASH resolution without worsening of fibrosis, or both fibrosis improvement and MASH resolution.
Sixty-seven patients completed the treatment, and 65 post-baseline biopsies were collected — 34 in the placebo group and 31 in the treatment group.
Positive Results
“We saw statistically significant changes in fibrosis improvement,” Koziel said. “This has been the hardest barrier to hit.”
After 24 weeks, 45% of patients in the treatment group and 21% in the placebo group showed fibrosis improvement of one or more stages without worsening of MASH (P = .038), and 68% of those in the treatment group and 29% in the placebo group had MASH resolution without fibrosis worsening (P = .002).
The between-group difference in fibrosis improvement and MASH resolution did not reach statistical significance, with 39% of patients in the treatment group and 18% in the placebo group achieving the combined endpoint (P = .066). “It just missed statistical significance,” Koziel said, but she viewed the outcome as meaningful.
Additionally, “a third of the group taking efimosfermin normalized their liver fat, and all but one normalized their liver enzymes,” she said.
Adverse events — most often nausea, vomiting and diarrhea — were mild to moderate in both groups, Koziel said. In the treatment group, one patient withdrew from the study due to a grade 3 serious adverse event, and two others did so due to low-grade adverse events.
“These data support further development of once-monthly efimosfermin for the treatment of MASH-related fibrosis,” the research team concluded.
Hopeful Development
“Finally, there’s hope,” said DDW attendee Na Li, MD, associate clinical professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, Ohio, whose clinical focus is on metabolic-associated steatotic liver disease.
The new hope, she said, refers not only to the phase 2 study results but to the Food and Drug Administration approval of resmetirom (Rezdiffra) last year, which reduces liver fat by stimulating thyroid hormone receptor beta. “That was the first medication that got approved with a specific indication to treat MASH,” she said. Before that, lifestyle measures aimed at weight loss were the only approach.
Lifestyle measures are still important, Li said, but it’s helpful to have additional options. “There are quite a few agents in the pipeline now,” she said. One example is another FGF21 analogue efruxifermin, which is in phase 3 trials.
Li had no disclosures. Koziel declared being an employee of Boston Pharmaceuticals.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Endoscopic Procedure Shows Promise in Type 2 Diabetes Care
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
SAN DIEGO – .
In a new dose-finding study, the re-cellularization via electroporation therapy (ReCET, Endogenex) improved insulin sensitivity, beta-cell function, and other glycemic parameters at 12 and 48 weeks in 51 individuals with T2D. “The findings suggest that duodenal mucosal and submucosal recellularization are key therapeutic targets in type 2 diabetes management,” said Barham Abu Dayyeh, MD, director of Interventional Gastroenterology at Cedar-Sinai Hospital, Los Angeles, in a presentation at Digestive Disease Week (DDW) 2025.
The outpatient technique is based on pulsed electrical fields, or electroporation, which do not use heat. “It’s nonthermal regeneration, not just ablation. It’s regeneration of the duodenum as a treatment target that could potentially modify type 2 diabetes,” Abu Dayyeh told GI & Hepatology News.
Separately at DDW, Abu Dayyeh presented results from an artificial intelligence–based analysis of duodenal biopsies from 111 individuals with T2D and 120 control individuals without diabetes, demonstrating distinct mucosal features associated with metabolic disease, significant inflammation in the deep mucosa and submucosa with increased fibrosis, and gut-barrier dysfunction. The authors termed this set of abnormalities “diabetic duodenopathy.”
Abu Dayyeh likened the duodenum to a “conductor” of the “dysfunctional orchestra” of metabolic disease that includes T2D. “It’s tasked with integrating signals from the food that we eat and from our microbiome and communicates that metabolic response to downstream organs like the pancreas, liver, and adipose tissue.”
Currently, he said, “We use treatments that work downstream on components of this dysfunctional orchestra. So we work on the violinist and the flute player, but we do not go upstream to say maybe there’s an opportunity to put the orchestra conductor back in synch…We manage blood glycemia by lowering it, rather than looking at upstream disease-modifying targets that could reverse the course so you require less insulin and less medication.”
Abu Dayyeh envisions the ReCET procedure as an option for people struggling to control T2D with standard medications, or for early use to avoid or delay medications, particularly insulin. But it won’t replace medications. “On the contrary, I see it as enhancing and complementing medications,” he said.
Asked to comment, Ali Aminian, MD, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic, Cleveland, Ohio, told GI & Hepatology News, “Diabetes is a heterogeneous disease complex with numerous pathophysiological derangements. Although diabetic duodenopathy can be seen in some patients with diabetes, that wouldn’t explain the entire story behind diabetes pathogenesis in all people with diabetes. In a subgroup of people with duodenal involvement in their disease process, endoscopic procedures targeting the duodenum may play a role in the future.”
Glycemic Parameters Improve Following ReCET Procedure
The new study, called REGENT-1, was a multicenter, open-label, single-arm dose escalation of three levels of energy delivery in patients who had T2D for 10 years or less with A1c levels 7.5%-11% despite the use of one or more noninsulin glucose-lowering medications. Procedural success, defined as treatment of at least 6 cm of duodenum, was achieved in 100% of participants.
From a baseline A1c of 8.6%, there were dose-response drops at weeks 12 and 48 by energy delivery, with significant reductions at week 48 of 1.00 and 1.70 percentage points, respectively, among the 18 who received the middle dose and the 21 given the highest dose. Body weight also dropped in all three groups in a dose-response way, from 1.2% with the lowest to 6.2% with the highest energy delivery.
In mixed-meal tolerance testing, glucose area under the curve, homeostatic model assessment for insulin resistance, sensitivity index, beta-cell function, and disposition index (a measure of beta-cell response to insulin resistance) were all reduced from baseline at 48 weeks after ReCET, reaching statistical significance with the highest energy dose.
There were no device- or procedure-related serious adverse events.
Based on a literature search, Abu Dayyeh found that modern glucagon like peptide-1 receptor agonist medications have a stronger effect than ReCET or Roux-en-Y gastric bypass (RYGB) on beta-cell function (increases by 239% with semaglutide and 314% with tirzepatide vs 50% with ReCET and 74% for RYGB). However, ReCET procedure produced superior results for both insulin sensitivity (+487% for ReCET and +326% for bypass vs 30% and 62%, respectively for semaglutide and tirzepatide) and disposition index (+1032% for ReCET, +667% with tirzepatide, +642% for RYGB, and +367% for semaglutide).
Aminian commented, “The findings of this single arm clinical trial are promising. The next step is to incorporate a blinded control group who undergoes an endoscopy without any therapeutic intervention.”
In fact, such a study is underway. Results of “a multicenter, randomized, double-blind, sham-controlled study for assessing the safety and effectiveness of endoscopic intestinal re-cellularization therapy in individuals with type 2 diabetes (ReCET)” are expected in late 2026.
In the meantime, Amanian said about the current findings, “I’d argue that the observed improvement in diabetes parameters can be related to more intensive medical therapy during follow-up in this single arm study.”
In the trials, the procedure takes 30 minutes to an hour to perform. However, as the technology improves, “the vision of this is to be a 20-minute outpatient procedure eventually,” Abu Dayyeh said.
He envisions that eventually the procedure will become as accessible as colonoscopy is now, and that primary care physicians and endocrinologists would similarly refer patients to a gastroenterologist or surgeon to have it done. “They do the procedure and send your patient back, hopefully with a less complex management strategy, so you could manage them more efficiently without escalating care.”
Abu Dayyeh is a co-inventor of the ReCET procedure, with the technology licensed by the Mayo Clinic. He is a consultant for and/or reported receiving research support from Boston Scientific, Olympus, Medtronic, Metamodix, BFKW, Apollo Endosurgery, USGI, Endogastric Solutions, Spatz, and Cairn. Aminian had received grants and personal fees from Medtronic and Ethicon. He serves as a consultant for Medtronic, Ethicon, and Eli Lilly.
A version of this article appeared on Medscape.com.
FROM DDW 2025
Semaglutide Therapy Improves Liver Histology in MASH
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
, an ongoing randomized placebo-controlled trial reported.
The glucagon-like peptide 1 receptor agonist (GLP-1 RA) is currently a candidate for treating MASH.
Preliminary results of the two-part phase 3, double-blind ESSENCE trial, conducted in at 253 clinical sites in 37 countries, were published in The New England Journal of Medicine.
A previous phase 2 study by Loomba et al suggested semaglutide was effective in reducing liver injury. “That study, however, did not show improvement in liver fibrosis, which this study has done,” study co-lead Philip Newsome, PhD, professor in the department of immunology and immunotherapy and Honorary Professor of Experimental Hepatology at the University of Birmingham in England, said in an interview.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard.”
Study Details
From May 2020 to April 2023, researchers led by Newsome and Arun J. Sanyal, MBBS, MD, of Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University School of Medicine, Richmond, randomized 1197 patients with a mean age of 56 years. Of these, 57% were women and 67.5% were White individuals. Mean body mass index was 34.6, and 55.9% had type 2 diabetes.
All had biopsy-defined MASH and fibrosis stage 2 or 3 according to the Nonalcoholic Steatohepatitis Clinical Research Network classification and a Nonalcoholic Fatty Liver Disease Activity Score ≥ 4.
Rates of fibrosis were 31.3% for stage 2 fibrosis and 68.8% for stage 3. Diverse geographic site locations included Asia (25.1%), Europe (25.3%), North America (35.0%), and South America (7.9%), and others (6.8%).
In a 2:1 ratio, they were assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. A planned interim analysis of the first 800 patients was done at week 72, with primary endpoints being resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.
Resolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% CI, 21.1-36.2, P < .001).
A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of semaglutide recipients and 22.4% of placebo recipients (estimated difference, 14.4 percentage points; 95% CI, 7.5-21.3, P < .001).
In secondary findings, the combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% in the semaglutide group vs 16.1% in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2-22.8; P < .001).
The mean change in body weight was –10.5% with semaglutide and –2.0% with placebo (estimated difference, –8.5 percentage points; 95% CI, –9.6 to –7.4, P < .001). Mean changes in bodily pain scores did not differ significantly between arms.
The histologic benefits of semaglutide also emerged in improvements on all prespecified noninvasive tests — including aspartate transaminase and alanine transaminase levels and liver stiffness. Emerging evidence has suggested an association between reductions in liver stiffness and clinical benefit.
Gastrointestinal adverse events were more common in the semaglutide group.
Commenting on the study from a nonparticipant’s perspective, Naga P. Chalasani, MD, AGAF, professor of gastroenterology and hepatology at Indiana University School of Medicine, Indianapolis, said results from the ESSENCE trial were “long awaited and they certainly advance the field of MASH clinical trials substantially.”
Furthermore, he added, the results are well aligned with those of a phase 2b trial of semaglutide by Newsome and colleagues for what was then termed nonalcoholic steatohepatitis, and “they also align with what is known about the positive role of incretins, digestive hormones imitated by GLP-1s to improve liver health in patients with MASLD and MASH.”
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis,” Chalasani said. “More than 80% of patients with MASH and fibrosis have either diabetes and/or obesity.”
He added that a better understanding is needed of how semaglutide works in patients with MASH cirrhosis since the previous small study was unsuccessful. “But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology.”
According to Newsome, GLP-1s will become the backbone of therapy in MASH given their range of metabolic and liver benefit. But questions remain, he said. “Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
This study was supported by Novo Nordisk, the manufacturer of Wegovy. Sanyal reported having various financial relationships with multiple private-sector companies, including Novo Nordisk. Newsome reported consulting for Novo Nordisk and Boehringer Ingelheim. Several study coauthors reported having similar relationships with pharmaceutical companies or employment with Novo Nordisk. Chalasani declared being involved in several MASH clinical trials conducted by other pharmaceutical companies.
A version of this article appeared on Medscape.com.
Histamine Pathway a Target for Erythropoietic Protoporphyria?
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
Mutations in the ferrochelatase (FECH) gene cause erythropoietic porphyria. EPP is characterized biochemically by liver and bone marrow accumulation of protoporphyrin-IX (PP-IX), and is characterized clinically by hepatic dysfunction with progression in 1-4% to advanced liver disease.
A recent study by Kuo and colleagues exemplifies a bench-to-bedside evolution comprising pharmacological screening, mechanistic dissection, and ultimately translation of this mechanism to human subjects to treat EPP. They utilized high-throughput compound screening in a zebrafish model to identify the anti-histamine, chlorcyclizine (CCZ), as a candidate EPP therapy. Chlorciclizine lowered hepatocyte PP-IX in multiple EPP models by blocking peripheral histamine production, and by inducing hepatocyte PP-IX efflux. The data represent advances in the realms of both clinical therapeutics and molecular pathophysiological discovery.
From a discovery standpoint, strategic compound screening that utilizes the LOPAC (library of pharmaceutically active compounds) and Prestwick libraries offers at least two key characteristics. First, these compounds have largely known targets. The known pharmacology of chlorcyclizine provided immediate clues to validate mechanism rapidly in hepatic HPP, a relatively poorly understood disease. Moreover, screening libraries comprising FDA-approved drugs can minimize lag time between discovery and translation to interventional trials in human subjects.
Beyond such strategic discovery considerations, perhaps more exciting is the therapeutic potential for anti-histaminergic therapy to mitigate hepatic manifestations in EPP. Specifically, other porphyrias with hepatic complications have FDA-approved treatments, such as anti-ALAS1 siRNAs to treat acute hepatic porphyria (AHP). No such treatment currently exists for liver dysfunction in EPP, yet CCZ and other histamine-1 receptor blockers hold such promise. Indeed, the H1 inhibitor, cimetidine, is currently in an active phase 2 trial to treat EPP (NCT05020184).
Given the already widespread use of antihistamines to symptomatically treat cutaneous EPP, we may not be too distant from pivoting and deploying readily available H1Bs like cimetidine to treat EPP liver manifestations as well. Given recent data by Kuo and colleagues, such an outcome should not be too far-FECHed.
Brian DeBosch, MD, PhD, is Center Director of the nutrition & molecular metabolism research program, in the Division of Gastroenterology, Hepatology & Nutrition at Indiana University School of Medicine, Indianapolis. He declares no conflicts of interest.
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
An experimental study in zebrafish has suggested the decades-old, first-generation antihistamine chlorcyclizine and/or other antihistamines may be a strategy for treating erythropoietic protoporphyria (EPP)-associated liver disease by decreasing hepatic protoporphorin IX (PP-IX) accumulation.
Currently, liver transplantation is the primary treatment for this rare, painful, and life-threatening genetic disease, which is caused by excessive PP-IX accumulation and affects about 4000 people in the United States.
The findings could eventually lead to a simpler treatment that prevent shepatic damage at a much earlier stage, according to researchers led by M. Bishr Omary, MD, PhD, a professor in the Center for Advanced Biotechnology and Medicine and Robert Wood Johnson Medical School at Rutgers University in Piscataway, New Jersey.
Reporting in Cellular and Molecular Gastroenterology and Hepatology, the investigators found that chlorcyclizine reduced PP-IX levels. EPP is caused by mutations leading to deficiency of the enzyme ferrochelatase, which inserts iron into PP-IX to generate heme. The resulting condition is characterized by PP-IX accumulation, skin photosensitivity, cholestasis, and end-stage liver disease. “Despite available drugs that address photosensitivity, the treatment of EPP-related liver disease remains an unmet need,” Omary and colleagues wrote.
The Study
In order to trigger PP-IX overproduction and accumulation, the investigators administered delta-aminolevulinic acid and deferoxamine to zebrafish. These freshwater tropical fish share many physiological characteristics with humans and have been used to model human disease and develop drugs. Furthermore, these fish are transparent at the larval stage, allowing quantification and visualization of porphyrin, which is fluorescent.
The researchers had screened some 2500 approved and bioactive compounds and identified chlorcyclizine as a potent PP-IX–lowering agent.
High-throughput compound screening of ALA + DFO-treated zebrafish found that the HH-1 blocker reduced zebrafish liver PP-IX levels. The effect of chlorcyclizine was validated in porphyrin-loaded primary mouse hepatocytes, transgenic mice, and mice fed the porphyrinogenic compound 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Plasma and tissue PP-IX were measured by fluorescence; livers were analyzed by histology, immunoblotting, and quantitative polymerase chain reaction.
Chlorcyclizine-treated zebrafish larvae as well as the two types of mice all showed reduced hepatic PP-IX levels compared with controls. While the neurotransmitter played an important role in PP-IX accumulation in porphyrin-stressed hepatocytes, blockading notably decreased PP-IX levels.
Detailed analysis showed that chlorcyclizine appeared to work through multiple mechanisms, helping the liver clear toxic porphyrin buildup and reducing inflammation. It also decreased the presence of histamine-producing mast cells. The result was less liver injury, decreased porphyrin-triggered protein aggregation and oxidation, and increased clearance of s PP-I in stool.
Interestingly, in both mouse models, chlorcyclizine lowered PP-IX levels in female but not male mice in liver, erythrocytes, and bone marrow. This sex-specific effect appeared to be related to the greater speed at which male murines metabolize the drug, the authors explained in a news release. In rats, for example, the metabolism of chlorcyclizine is 8 times higher in male than in female livers.
The investigators plan to launch a clinical trial in EPP patients to evaluate the effectiveness of chlorcyclizine for both liver and skin involvement. And a phase 2 trial is already underway testing the antacid cimetidine for treating EPP skin manifestations. It is possible that the different antihistamines may act additively or synergistically.
This work was supported by National Institutes of Health (NIH) grants and the Henry and Mala Dorfman Family Professorship of Pediatric Hematology/Oncology.
Omary is a member of the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Data and Safety Monitoring Board of the Porphyrias Consortium.
A provisional patent application has been submitted for the use of H1-receptor blockers with or without receptor blockers to treat protoporphyrias associated with PP-IX accumulation.
From Cellular and Molecular Gastroenterology and Hepatology
IgG-Guided Elimination Diet Beats Sham Diet for IBS Pain
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
Symptoms in most people with irritable bowel syndrome (IBS) are perceived to be closely linked to diet. The low FODMAP diet has been pivotal for the treatment of IBS, and a range of other diet approaches are now on the research horizon.
Whilst IgE-mediated allergy is relatively rare, there has been research suggesting a role of IgG-mediated food sensitivity in causing symptoms in IBS, although the role of IgG testing and dietary elimination has been controversial. This study from Singh and colleagues suggests an IgG-based elimination diet could improve abdominal pain and global symptoms in two thirds of people with Rome IV IBS. Critically, the study is one of the largest so far and provides the most robust and detailed description of the trial diets to date.
The potential of a new diet approach is extremely appealing, especially as the low FODMAP diet is not universally effective. However, there is still some work to be done to transition the IgG-based elimination diet into guidelines and routine practice. Notably, some common foods restricted in IgG-based elimination diets are also high in FODMAPs leaving questions about the true driver of symptom benefit. Should convincing mechanistic studies and further additional RCT data validate these findings, this could present a major step forward for personalised nutrition in IBS.
Heidi Staudacher, PhD, is associate professor in the School of Translational Medicine, Monash University, Melbourne, Australia. She declared no conflicts of interest.
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
An irritable bowel syndrome (IBS) elimination diet based on a novel IBS–specific, immunoglobulin G (IgG) was superior to a sham diet for abdominal pain, an 8-center, randomized double-blind controlled trial found.
While elimination diets can provide a personalized approach to dietary therapy, existing studies have had serious methodological issues, noted lead author Prashant Singh, MBBS, of the Division of Gastroenterology and Hepatology, Department of Internal Medicine, Michigan Medicine, Ann Arbor, Mich., and colleagues in Gastroenterology.
For example, previous studies on IgG-based diets used assays developed without determining IBS trigger foods or establishing a 95% confidence interval–based cutoff using a healthy control comparison group.
Study Details
From June 2018 to December 2021, 238 IBS patients testing positive for at least one food on 18-food IgG ELISA (enzyme-linked immunosorbent assay) testing and an average daily abdominal pain intensity score of 3.0 to 7.5 on an 11.0-point scale during a 2-week run-in period were randomized for 8 weeks to an experimental antibody-guided diet or to a sham diet. The primary outcome was a 30% decrease in abdominal pain intensity (API) for 2 of the last 4 weeks of treatment.
The overall study population had a mean age of about 40 years, and more than three-quarters were female. The 3 IBS types – constipation-predominant (IBS-C), diarrhea-predominant (IBS-D), and mixed bowel habits-predominant (IBS-M) – accounted for about a third each in both arms.
The experimental diet eliminated foods based on a positive ELISA result. Its sham counterpart had the same number of foods removed as the number of positive-testing food sensitivities, but the foods eliminated in the sham diet had tested negative on the IgG assay.
Participants reported daily abdominal pain intensity, bloating, and stool consistency, and frequency. They also reported dietary compliance and daily medication use.
Of the 238 randomized adults, 223 were included in the modified intention-to-treat analysis. A significantly greater proportion of subjects in the experimental group met the primary outcome than those in the sham group: 59.6% vs 42.1%, P = .02). “This highlights the potential effectiveness of a personalized elimination diet based on a novel IBS-specific IgG assay,” the authors wrote.
Symptom improvement between arms began to separate out at around 2 weeks, suggesting the effect of the experimental diet was relatively rapid in onset, and continued for at least 8 weeks. The durability of response, however, needs to be assessed in future studies “and it is unclear if there is a role for repeat IgG testing to monitor treatment response,” the authors wrote.
Subgroup analysis revealed that a higher proportion of those with IBS-C and IBS-M in the experimental diet group met the primary endpoint vs the sham group: 67.1% vs 35.8% and 66% vs 29.5%, respectively.
Interestingly, more patients in the experimental arm were noncompliant with their diet. “It is possible that subjects found the experimental diet more difficult to comply with compared with the sham diet or that because the experimental diet was more likely to improve symptoms, dietary indiscretion may have been more common in this group (a phenomenon seen with other elimination diets such as gluten-free diet in celiac disease),” the authors wrote.
Adverse events, deemed unrelated to either regimen, were 3 in the experimental arm vs 8 in the sham arm, which had 2 urinary tract infections.
The authors called for a larger, adequately powered study to assess the efficacy of an elimination diet based on this novel immunoglobulin G assay in patients with IBS-C and IBS-M. Future studies should perform detailed adherence assessments using food diaries.
“Mechanisms of how immunoglobulin G-antibody response to food antigen generates symptoms in irritable bowel syndrome are not well understood. Delineating this might provide new insights into food-related irritable bowel syndrome pathophysiology,” they concluded.
This study was funded by Biomerica Inc.
FROM GASTROENTEROLOGY