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Wearable Device Tracks IBD from Sweat
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
LAS VEGAS —
The device, in development by EnLiSense, can rapidly detect calprotectin, C-reactive protein (CRP), and interleukin-6 (IL-6), using miniaturized versions of biochemical lab tests.
Patient monitoring relies on identifying trends, whether biomarker levels are increasing or decreasing, according to Shalini Prasad, PhD, who presented the study during a poster session at the annual Crohn’s & Colitis Congress®, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “In a blood test you don’t get that unless you’re willing to sample every month. That’s the benefit [of the device],” said Dr. Prasad, professor of bioengineering at University of Texas at Dallas and a cofounder of EnLiSense.
The project grew out of the involvement of EnLiSense with the Biomedical Advanced Research Development Authority (BARDA). “We were tracking infections, and we were looking at inflammatory markers associated with infections: Cytokines and chemokines. We thought it was a natural pivot for us because the disease of inflammation is IBD,” said Dr. Prasad.
The device need only be worn when the physician determines the disease is in a variable state. The patient “will wear it for the duration of time as determined by the clinician,” said Dr. Prasad.
The watch face–sized device, typically worn on the forearm, absorbs sweat and performs automated biochemical analysis independently, then beams its findings to the cloud. “What you get back is concentration [of inflammatory biomarkers]. It is essentially trend line reporting of how the concentration is fluctuating over time for markers,” said Dr. Prasad.
The Crohn’s and Colitis Foundation is supporting the company through its IBD Ventures program. EnLiSense is currently conducting a study tracking patients over 4 weeks to correlate biomarker concentrations in sweat with concentrations in stool.
A key remaining question is how long the device should be worn and during what clinical periods. The technology has the potential to provide too much information. “Just figuring the balance. We’re trying to find the right spot where it makes sense for both the clinician and the patient. This is something that is a work in progress. We don’t want this to be just like any other consumer wearable which gives you something but you’re not sure what it means,” said Dr. Prasad.
The study included 33 patients with IBD who were monitored between 40 and 130 minutes. The device measured levels of CRP, IL-6, and calprotectin. Serum samples were also measured the same day.
The researchers found higher levels of calprotectin among patients with active disease in perspiration (P = .0260), serum (P = .022), and in fecal samples (P = .0411). There were no significant differences between patients who are active and those in remission with respect to CRP levels in perspiration or serum, or IL-6 in perspiration. Serum Il-6 levels were higher in those with active disease.
There was no significant difference between serum and sweat calprotectin levels among patients who were active or in remission, but the median expression of IL-6 in perspiration was higher in the active group (P = .0016). In the active group, calprotectin was elevated in sweat, serum, and stool.
Levels of calprotectin measured in perspiration correlated with levels in the serum (R2 = 0.7195), as did CRP (R2 = 0.615) and IL-6 (R2 = 0.5411).
Treating to Target
The poster caught the interest of Jeremiah Faith, PhD, who attended the session and was asked to comment. “I think patients want to know what’s happening [with their disease], and we could probably give better care if we know day to day the status of someone, especially because every time we test them we get a point in time, but the reality is probably that people are kind of wavy, and knowing the wave is much better,” he said.
He noted that there was not a strong separation between mean perspiration calprotectin values, but he said the ability to take frequent measurements could overcome that weakness. “The difference between active and remission is not as drastic as what you’d see from blood, for example. But it’s the same thing with your watch. Your watch is a really poor sensor of what your heartbeat is doing, but if you measure it every few seconds, and you average over a long period of time, it can actually more be more [accurate]. So there’s a lot of potential for this,” said Dr. Faith, associate professor of genetics and genomic sciences at the Icahn School of Medicine at Mount Sinai in New York.
If perfected, the device could help efforts at treating to target, in which therapies are adjusted to achieve minimal disease. Currently, physicians are forced to adjust doses or change therapies based on infrequent testing. “If this is accurate ... maybe at some point we will have the tools to be smarter about it,” said Dr. Faith.
Dr. Prasad is a cofounder of EnLiSense. Dr. Faith has no relevant financial disclosures.
FROM CROHN’S & COLITIS CONGRESS
Ultrasound Monitoring of IBD May Prompt Faster Treatment Change
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
FROM ACG 2023
February 2024 – ICYMI
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Gastroenterology
October 2023
El-Salhy M et al. Efficacy of Fecal Microbiota Transplantation for Patients With Irritable Bowel Syndrome at 3 Years After Transplantation. Gastroenterology. 2022 Oct;163(4):982-994.e14. doi: 10.1053/j.gastro.2022.06.020. Epub 2022 Jun 14. PMID: 35709830.
Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-851. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.
Lo CH et al. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. doi: 10.1053/j.gastro.2022.06.067. Epub 2022 Jul 1. PMID: 35788344; PMCID: PMC9509450.
November 2023
Khoshiwal AM et al. The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia. Gastroenterology. 2023 Nov;165(5):1168-1179.e6. doi: 10.1053/j.gastro.2023.07.029. Epub 2023 Aug 30. PMID: 37657759.
Chen YI et al. Endoscopic Ultrasound-Guided Biliary Drainage of First Intent With a Lumen-Apposing Metal Stent vs Endoscopic Retrograde Cholangiopancreatography in Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Study (ELEMENT Trial). Gastroenterology. 2023 Nov;165(5):1249-1261.e5. doi: 10.1053/j.gastro.2023.07.024. Epub 2023 Aug 6. PMID: 37549753.
December 2023
Almario CV et al. Prevalence and Burden of Illness of Rome IV Irritable Bowel Syndrome in the United States: Results From a Nationwide Cross-Sectional Study. Gastroenterology. 2023 Dec;165(6):1475-1487. doi: 10.1053/j.gastro.2023.08.010. Epub 2023 Aug 16. PMID: 37595647.
Koopmann BDM et al. The Natural Disease Course of Pancreatic Cyst-Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model. Gastroenterology. 2023 Dec;165(6):1522-1532. doi: 10.1053/j.gastro.2023.08.027. Epub 2023 Aug 24. PMID: 37633497.
Clinical Gastroenterology and Hepatology
October 2023
Jung DH et al. Comparison of a Polysaccharide Hemostatic Powder and Conventional Therapy for Peptic Ulcer Bleeding. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2844-2253.e5. doi: 10.1016/j.cgh.2023.02.031. Epub 2023 Mar 10. PMID: 36906081.
Liang PS et al. Blood Test Increases Colorectal Cancer Screening in Persons Who Declined Colonoscopy and Fecal Immunochemical Test: A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2023 Oct;21(11):2951-2957.e2. doi: 10.1016/j.cgh.2023.03.036. Epub 2023 Apr 8. PMID: 37037262; PMCID: PMC10523873.
November 2023
Li YK et al. Risk of Postcolonoscopy Thromboembolic Events: A Real-World Cohort Study. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3051-3059.e4. doi: 10.1016/j.cgh.2022.09.021. Epub 2022 Sep 24. PMID: 36167228.
Tome J et al. Bile Acid Sequestrants in Microscopic Colitis: Clinical Outcomes and Utility of Bile Acid Testing. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3125-3131.e2. doi: 10.1016/j.cgh.2023.04.031. Epub 2023 May 10. PMID: 37172800.
Berry SK et al. A Randomized Parallel-group Study of Digital Gut-directed Hypnotherapy vs Muscle Relaxation for Irritable Bowel Syndrome. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3152-3159.e2. doi: 10.1016/j.cgh.2023.06.015. Epub 2023 Jun 28. PMID: 37391055.
December 2023
Kanwal F et al. Risk Stratification Model for Hepatocellular Cancer in Patients With Cirrhosis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3296-3304.e3. doi: 10.1016/j.cgh.2023.04.019. Epub 2023 Apr 30. PMID: 37390101; PMCID: PMC10661677.
Forss A et al. Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3356-3364.e9. doi: 10.1016/j.cgh.2023.05.014. Epub 2023 May 26. PMID: 37245713.
Zheng T et al. A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis. Clin Gastroenterol Hepatol. 2023 Dec;21(13):3405-3414.e4. doi: 10.1016/j.cgh.2023.07.008. Epub 2023 Jul 22. PMID: 37482172.
Techniques and Innovations in Gastrointestinal Endoscopy
Rengarajan A and Aadam A. Peroral Endoscopic Myotomy (POEM) and Its Use in Esophageal Dysmotility. Tech Innov Gastrointest Endosc. 2023 Dec 16. doi: 10.1016/j.tige.2023.12.004.
Wang D et al. Sphincterotomy vs Sham Procedure for Pain Relief in Sphincter of Oddi Dysfunction: Systematic Review and Meta-analysis. Tech Innov Gastrointest Endosc. 2023 Nov 7. doi: 10.1016/j.tige.2023.10.003
Gastro Hep Advances
Gregory MH et al. Short Bowel Syndrome: Transition of Pediatric Patients to Adult Gastroenterology Care. Gastro Hep Advances. 2023 Sep 8. doi: 10.1016/j.gastha.2023.09.006.
Viser AC et al. Inflammatory Bowel Disease Patients in the Ambulatory Setting Commonly Screen Positive for Malnutrition. Gastro Hep Advances. 2023 Nov 16. doi: 10.1016/j.gastha.2023.11.007.
Tenapanor Shows Response in IBS-C Within Weeks: Pooled Data Analysis
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
FROM ACG 2023
IBS Meta-Analysis Offers Some Support for Mesalamine
Certain patients with irritable bowel syndrome (IBS) may benefit from treatment with mesalamine, although the quality of evidence supporting this strategy remains low, according to a recent systematic literature review and meta-analysis.
Global IBS symptoms improved significantly across the entire population, however, a subgroup analysis suggested that mesalamine may be most beneficial for patients who present with diarrhea, providing support for a large clinical trial in this patient population, reported lead author Vivek C. Goodoory, MBChB, of St. James’s University Hospital, Leeds, United Kingdom, and colleagues.
Some patients with IBS may present with low-grade inflammation in the intestine, offering theoretical grounds for prescribing mesalamine, which is typically used for treating ulcerative colitis, the investigators wrote in Clinical Gastroenterology and Hepatology. Yet previous randomized controlled trials (RCTs) evaluating mesalamine for IBS have yielded mixed results, and a meta-analysis showed that mesalamine offered no benefit.
According to Dr. Goodoory and colleagues, however, that meta-analysis fell short since it “only pooled mean symptom scores, rather than the proportion of patients in each trial experiencing an improvement in symptoms, and did not appear to include data from all available RCTs.” Furthermore, they noted that this prior study lacked subgroup analyses conducted based on IBS subtype or postinfection status.
“We, therefore, conducted a contemporaneous meta-analysis to examine the efficacy and safety of mesalamine in IBS addressing these deficits in knowledge,” the investigators wrote.
Their meta-analysis included 820 patients from 8 RCTs published between 2009 and 2022. Efficacy and safety were evaluated via dichotomous assessments of global IBS symptoms, bowel habit or stool frequency, abdominal pain, and adverse events. Two subgroup analyses were planned to evaluate responses based on post-infection status and predominant stool pattern.
Unlike the previous meta-analysis, Dr. Goodoory and colleagues detected a potential signal for efficacy.
Across all patients, mesalamine was associated with significant improvement in global IBS symptoms, compared with placebo (relative risk [RR], 0.86; 95% CI, 0.79-0.95). However, no significant improvements were detected for abdominal pain or bowel habit/stool frequency.
A subgroup analysis of patients exhibiting IBS with diarrhea showed significantly greater improvements in global IBS symptoms for mesalamine versus placebo (RR, 0.88; 95% CI, 0.79-0.99). This subgroup showed no improvements in abdominal pain or bowel habit/stool frequency.
Subgroup analyses for patients with constipation or mixed bowel habits, or based on postinfection status, revealed no significant differences, although the investigators noted that relevant data were limited.
Mesalamine appeared to be well tolerated. Across five studies reporting adverse events, 43.5% of patients receiving mesalamine reported any adverse event, compared with 41.4% of patients on placebo. The RR of experiencing an adverse event in those taking mesalamine was 1.20 (95% CI, 0.89-1.63), which was not statistically significant.
“There was no evidence of heterogeneity between studies in most of our analyses, but only one trial was at low risk of bias across all domains, and there were insufficient studies to assess for funnel plot asymmetry,” Dr. Goodoory and colleagues wrote. “Based on these limitations of the evidence,” they continued, “our confidence in the results of the meta-analysis would be low, and further large trials at low risk of bias would be informative.”
Specifically, the investigators suggested an RCT recruiting only patients with IBS with diarrhea, and reporting efficacy according to postinfection status.
One coauthor reported research funding from Tillotts Pharma and Dr Falk Pharma UK. The remaining authors reported no conflicts.
Advancements in the understanding of irritable bowel syndrome (IBS) pathophysiology have led to new pharmacological agents and guidelines on the delivery of patient-specific IBS care. However, treatments targeting specific IBS mechanisms including altered immune responses, barrier dysfunction, and low-grade inflammation are lacking.
In a systematic review and meta-analysis, Goodoory et al. find that pooled results from six randomized controlled trials suggest efficacy with mesalamine, an anti-inflammatory agent, for global IBS symptoms with subgroup analyses further suggesting efficacy in IBS with diarrhea. However, results are tempered by the overall low quality of evidence and lack of benefit for abdominal pain or bowel habits. Notably, the only study rated as low risk of bias did not find mesalamine to be effective. Thus, these findings cannot yet be used to inform clinical decision-makers.
Still, further study is warranted. Such future work will benefit from including well-phenotyped patients and novel biomarkers with the ability to identify individuals in whom inflammatory mechanisms contribute to IBS symptoms.
Dr. Andrea Shin is based in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California Los Angeles. She is a member of the editorial boards of Clinical Gastroenterology and Hepatology, and Alimentary Pharmacology & Therapeutics. She is associate clinical editor of Neurogastroenterology & Motility, and a member of the Scientific Communications Advisory Board for IBS-C. As an AGA member, she sits on the Research Awards Panel, and is a section councilor for neurogastroenterology & motility, as well as a patient education advisor. Dr. Shin has received funding from the NIH R03 Limited Competiation Small Grant Program, an ANMS Diversity Development Award, and is an NIH Loan Repayment Program Awardee. She has no other relevant disclosures.
Advancements in the understanding of irritable bowel syndrome (IBS) pathophysiology have led to new pharmacological agents and guidelines on the delivery of patient-specific IBS care. However, treatments targeting specific IBS mechanisms including altered immune responses, barrier dysfunction, and low-grade inflammation are lacking.
In a systematic review and meta-analysis, Goodoory et al. find that pooled results from six randomized controlled trials suggest efficacy with mesalamine, an anti-inflammatory agent, for global IBS symptoms with subgroup analyses further suggesting efficacy in IBS with diarrhea. However, results are tempered by the overall low quality of evidence and lack of benefit for abdominal pain or bowel habits. Notably, the only study rated as low risk of bias did not find mesalamine to be effective. Thus, these findings cannot yet be used to inform clinical decision-makers.
Still, further study is warranted. Such future work will benefit from including well-phenotyped patients and novel biomarkers with the ability to identify individuals in whom inflammatory mechanisms contribute to IBS symptoms.
Dr. Andrea Shin is based in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California Los Angeles. She is a member of the editorial boards of Clinical Gastroenterology and Hepatology, and Alimentary Pharmacology & Therapeutics. She is associate clinical editor of Neurogastroenterology & Motility, and a member of the Scientific Communications Advisory Board for IBS-C. As an AGA member, she sits on the Research Awards Panel, and is a section councilor for neurogastroenterology & motility, as well as a patient education advisor. Dr. Shin has received funding from the NIH R03 Limited Competiation Small Grant Program, an ANMS Diversity Development Award, and is an NIH Loan Repayment Program Awardee. She has no other relevant disclosures.
Advancements in the understanding of irritable bowel syndrome (IBS) pathophysiology have led to new pharmacological agents and guidelines on the delivery of patient-specific IBS care. However, treatments targeting specific IBS mechanisms including altered immune responses, barrier dysfunction, and low-grade inflammation are lacking.
In a systematic review and meta-analysis, Goodoory et al. find that pooled results from six randomized controlled trials suggest efficacy with mesalamine, an anti-inflammatory agent, for global IBS symptoms with subgroup analyses further suggesting efficacy in IBS with diarrhea. However, results are tempered by the overall low quality of evidence and lack of benefit for abdominal pain or bowel habits. Notably, the only study rated as low risk of bias did not find mesalamine to be effective. Thus, these findings cannot yet be used to inform clinical decision-makers.
Still, further study is warranted. Such future work will benefit from including well-phenotyped patients and novel biomarkers with the ability to identify individuals in whom inflammatory mechanisms contribute to IBS symptoms.
Dr. Andrea Shin is based in the Vatche and Tamar Manoukian Division of Digestive Diseases at the University of California Los Angeles. She is a member of the editorial boards of Clinical Gastroenterology and Hepatology, and Alimentary Pharmacology & Therapeutics. She is associate clinical editor of Neurogastroenterology & Motility, and a member of the Scientific Communications Advisory Board for IBS-C. As an AGA member, she sits on the Research Awards Panel, and is a section councilor for neurogastroenterology & motility, as well as a patient education advisor. Dr. Shin has received funding from the NIH R03 Limited Competiation Small Grant Program, an ANMS Diversity Development Award, and is an NIH Loan Repayment Program Awardee. She has no other relevant disclosures.
Certain patients with irritable bowel syndrome (IBS) may benefit from treatment with mesalamine, although the quality of evidence supporting this strategy remains low, according to a recent systematic literature review and meta-analysis.
Global IBS symptoms improved significantly across the entire population, however, a subgroup analysis suggested that mesalamine may be most beneficial for patients who present with diarrhea, providing support for a large clinical trial in this patient population, reported lead author Vivek C. Goodoory, MBChB, of St. James’s University Hospital, Leeds, United Kingdom, and colleagues.
Some patients with IBS may present with low-grade inflammation in the intestine, offering theoretical grounds for prescribing mesalamine, which is typically used for treating ulcerative colitis, the investigators wrote in Clinical Gastroenterology and Hepatology. Yet previous randomized controlled trials (RCTs) evaluating mesalamine for IBS have yielded mixed results, and a meta-analysis showed that mesalamine offered no benefit.
According to Dr. Goodoory and colleagues, however, that meta-analysis fell short since it “only pooled mean symptom scores, rather than the proportion of patients in each trial experiencing an improvement in symptoms, and did not appear to include data from all available RCTs.” Furthermore, they noted that this prior study lacked subgroup analyses conducted based on IBS subtype or postinfection status.
“We, therefore, conducted a contemporaneous meta-analysis to examine the efficacy and safety of mesalamine in IBS addressing these deficits in knowledge,” the investigators wrote.
Their meta-analysis included 820 patients from 8 RCTs published between 2009 and 2022. Efficacy and safety were evaluated via dichotomous assessments of global IBS symptoms, bowel habit or stool frequency, abdominal pain, and adverse events. Two subgroup analyses were planned to evaluate responses based on post-infection status and predominant stool pattern.
Unlike the previous meta-analysis, Dr. Goodoory and colleagues detected a potential signal for efficacy.
Across all patients, mesalamine was associated with significant improvement in global IBS symptoms, compared with placebo (relative risk [RR], 0.86; 95% CI, 0.79-0.95). However, no significant improvements were detected for abdominal pain or bowel habit/stool frequency.
A subgroup analysis of patients exhibiting IBS with diarrhea showed significantly greater improvements in global IBS symptoms for mesalamine versus placebo (RR, 0.88; 95% CI, 0.79-0.99). This subgroup showed no improvements in abdominal pain or bowel habit/stool frequency.
Subgroup analyses for patients with constipation or mixed bowel habits, or based on postinfection status, revealed no significant differences, although the investigators noted that relevant data were limited.
Mesalamine appeared to be well tolerated. Across five studies reporting adverse events, 43.5% of patients receiving mesalamine reported any adverse event, compared with 41.4% of patients on placebo. The RR of experiencing an adverse event in those taking mesalamine was 1.20 (95% CI, 0.89-1.63), which was not statistically significant.
“There was no evidence of heterogeneity between studies in most of our analyses, but only one trial was at low risk of bias across all domains, and there were insufficient studies to assess for funnel plot asymmetry,” Dr. Goodoory and colleagues wrote. “Based on these limitations of the evidence,” they continued, “our confidence in the results of the meta-analysis would be low, and further large trials at low risk of bias would be informative.”
Specifically, the investigators suggested an RCT recruiting only patients with IBS with diarrhea, and reporting efficacy according to postinfection status.
One coauthor reported research funding from Tillotts Pharma and Dr Falk Pharma UK. The remaining authors reported no conflicts.
Certain patients with irritable bowel syndrome (IBS) may benefit from treatment with mesalamine, although the quality of evidence supporting this strategy remains low, according to a recent systematic literature review and meta-analysis.
Global IBS symptoms improved significantly across the entire population, however, a subgroup analysis suggested that mesalamine may be most beneficial for patients who present with diarrhea, providing support for a large clinical trial in this patient population, reported lead author Vivek C. Goodoory, MBChB, of St. James’s University Hospital, Leeds, United Kingdom, and colleagues.
Some patients with IBS may present with low-grade inflammation in the intestine, offering theoretical grounds for prescribing mesalamine, which is typically used for treating ulcerative colitis, the investigators wrote in Clinical Gastroenterology and Hepatology. Yet previous randomized controlled trials (RCTs) evaluating mesalamine for IBS have yielded mixed results, and a meta-analysis showed that mesalamine offered no benefit.
According to Dr. Goodoory and colleagues, however, that meta-analysis fell short since it “only pooled mean symptom scores, rather than the proportion of patients in each trial experiencing an improvement in symptoms, and did not appear to include data from all available RCTs.” Furthermore, they noted that this prior study lacked subgroup analyses conducted based on IBS subtype or postinfection status.
“We, therefore, conducted a contemporaneous meta-analysis to examine the efficacy and safety of mesalamine in IBS addressing these deficits in knowledge,” the investigators wrote.
Their meta-analysis included 820 patients from 8 RCTs published between 2009 and 2022. Efficacy and safety were evaluated via dichotomous assessments of global IBS symptoms, bowel habit or stool frequency, abdominal pain, and adverse events. Two subgroup analyses were planned to evaluate responses based on post-infection status and predominant stool pattern.
Unlike the previous meta-analysis, Dr. Goodoory and colleagues detected a potential signal for efficacy.
Across all patients, mesalamine was associated with significant improvement in global IBS symptoms, compared with placebo (relative risk [RR], 0.86; 95% CI, 0.79-0.95). However, no significant improvements were detected for abdominal pain or bowel habit/stool frequency.
A subgroup analysis of patients exhibiting IBS with diarrhea showed significantly greater improvements in global IBS symptoms for mesalamine versus placebo (RR, 0.88; 95% CI, 0.79-0.99). This subgroup showed no improvements in abdominal pain or bowel habit/stool frequency.
Subgroup analyses for patients with constipation or mixed bowel habits, or based on postinfection status, revealed no significant differences, although the investigators noted that relevant data were limited.
Mesalamine appeared to be well tolerated. Across five studies reporting adverse events, 43.5% of patients receiving mesalamine reported any adverse event, compared with 41.4% of patients on placebo. The RR of experiencing an adverse event in those taking mesalamine was 1.20 (95% CI, 0.89-1.63), which was not statistically significant.
“There was no evidence of heterogeneity between studies in most of our analyses, but only one trial was at low risk of bias across all domains, and there were insufficient studies to assess for funnel plot asymmetry,” Dr. Goodoory and colleagues wrote. “Based on these limitations of the evidence,” they continued, “our confidence in the results of the meta-analysis would be low, and further large trials at low risk of bias would be informative.”
Specifically, the investigators suggested an RCT recruiting only patients with IBS with diarrhea, and reporting efficacy according to postinfection status.
One coauthor reported research funding from Tillotts Pharma and Dr Falk Pharma UK. The remaining authors reported no conflicts.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Publishes New Pouchitis Management Guideline
The American Gastroenterological Association (AGA) has published a new clinical practice guideline on the management of pouchitis and inflammatory pouch disorders.
The guidance document, authored by Edward L. Barnes, MD, of the University of North Carolina at Chapel Hill and colleagues, includes eleven conditional recommendations that steer usage of probiotics, antibiotics, and immunosuppressive therapies in patients with these conditions, which occur most often after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC).
“Multiple strategies have been utilized in the treatment and prevention of pouchitis and inflammatory pouch conditions, including antibiotics, probiotics, corticosteroids, and advanced immunosuppressive therapies including biologics and oral small-molecule drugs,” the guideline panelists wrote on the AGA website. “However, most of the evidence base is primarily derived from retrospective observational studies or comparisons of small cohorts. Data on patients’ values and preferences for specific management decisions and treatment choices are also limited. This results in substantial practice variability.”
Still, the area is advancing. Dr. Barnes and colleagues highlighted new scoring systems for characterizing endoscopic findings and patient-reported outcomes, as well as the recent EARNEST trial (N Engl J Med. 2023 Mar 30;388(13):1191-1200), which compared vedolizumab with placebo in patients with chronic refractory pouchitis, and should be considered a “landmark study in the field,” as it could shape future trial design.
Based on all available evidence and clinical experience, the panelists issued the following recommendations, which were approved by the AGA Governing Board.
Probiotics
Because of a knowledge gap, the guideline makes no recommendation for or against use of probiotics for either the primary prevention or treatment of pouchitis.
They offered a similar explanation for the lack of guidance on using probiotics to treat pouchitis, and noted that antibiotics have demonstrated effectiveness where probiotics have not, making them the preferred treatment choice.
“There is potential that delaying therapy or using probiotics when they are not as effective as antibiotics may have significant impact on an individual patient’s quality of life,” Dr. Barnes and colleagues noted.
In contrast with the above statements, the guideline recommends usage of probiotics to prevent recurrent pouchitis in patients with recurrent, antibiotic-responsive pouchitis.
The De Simone formulation of multistrain probiotics is best supported in this scenario, the guideline notes, as this product was used in clinical trials, which collectively showed an 87% reduced risk of relapse over 12 months.
Antibiotics
Although the guideline supports antibiotics for prevention of pouchitis, the panelists noted that only one randomized controlled trial supports this recommendation, and negative effects of long-term usage need to be considered, including promotion of drug-resistant organisms and risk of Clostridioides difficile infection.
Dr. Barnes and colleagues cited more data supporting antibiotics for treatment of pouchitis, and noted that metronidazole and/or ciprofloxacin remain the preferred choices, with a typical duration of 2-4 weeks.
“An approach using a combination of antibiotics may be more effective in patients who do not respond to single-antibiotic therapy,” the panelists wrote, noting that oral vancomycin may also be considered when a patient does not respond to initial therapy.
For patients with recurrent pouchitis that relapses shortly after discontinuing antibiotics, chronic antibiotics should be considered, according to the guideline.
Immunosuppressive therapies
Advanced immunosuppressive therapies are recommended for patients with chronic antibiotic-dependent pouchitis, including those approved for treatment of UC or Crohn’s disease.
“Advanced immunosuppressive therapies may be used in lieu of chronic, continuous antibiotic therapy, particularly in patients who are intolerant to antibiotics or where patients and/or providers are concerned about risks of long-term antibiotic therapy,” the panelists wrote.
For patients with chronic antibiotic-refractory pouchitis, the guideline makes a general recommendation for advanced immunosuppressive therapies while specifically noting that vedolizumab has a greater strength of evidence in this scenario, citing the EARNEST trial.
A separate recommendation for corticosteroids is made for the same patient group, with ileal-release budesonide remaining the preferred formulation. In contrast, mesalamine is not recommended, based on a lack of supporting evidence.
Finally, the panelists recommend using corticosteroids in patients with Crohn’s-like disease of the pouch.
Future directions
“Even though pouchitis is relatively common after IPAA for UC, we observed that most of the evidence informing these guidelines was low to very low quality, derived from case series or small cohort studies, and several knowledge gaps exist,” Dr. Barnes and colleagues wrote. “Several initiatives towards improving management of inflammatory pouch disorders are already underway. However, concerted efforts in key domains are central towards improving patient care.”
They suggested that research should focus on standardizing disease entities, characterizing natural history and risk factors for inflammatory disorders of the pouch, and improving clinical trial design.The guideline was funded by the AGA Institute. The panelists disclosed relationships with Bristol-Myers Squibb, Sandoz, AbbVie, and others.
The American Gastroenterological Association (AGA) has published a new clinical practice guideline on the management of pouchitis and inflammatory pouch disorders.
The guidance document, authored by Edward L. Barnes, MD, of the University of North Carolina at Chapel Hill and colleagues, includes eleven conditional recommendations that steer usage of probiotics, antibiotics, and immunosuppressive therapies in patients with these conditions, which occur most often after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC).
“Multiple strategies have been utilized in the treatment and prevention of pouchitis and inflammatory pouch conditions, including antibiotics, probiotics, corticosteroids, and advanced immunosuppressive therapies including biologics and oral small-molecule drugs,” the guideline panelists wrote on the AGA website. “However, most of the evidence base is primarily derived from retrospective observational studies or comparisons of small cohorts. Data on patients’ values and preferences for specific management decisions and treatment choices are also limited. This results in substantial practice variability.”
Still, the area is advancing. Dr. Barnes and colleagues highlighted new scoring systems for characterizing endoscopic findings and patient-reported outcomes, as well as the recent EARNEST trial (N Engl J Med. 2023 Mar 30;388(13):1191-1200), which compared vedolizumab with placebo in patients with chronic refractory pouchitis, and should be considered a “landmark study in the field,” as it could shape future trial design.
Based on all available evidence and clinical experience, the panelists issued the following recommendations, which were approved by the AGA Governing Board.
Probiotics
Because of a knowledge gap, the guideline makes no recommendation for or against use of probiotics for either the primary prevention or treatment of pouchitis.
They offered a similar explanation for the lack of guidance on using probiotics to treat pouchitis, and noted that antibiotics have demonstrated effectiveness where probiotics have not, making them the preferred treatment choice.
“There is potential that delaying therapy or using probiotics when they are not as effective as antibiotics may have significant impact on an individual patient’s quality of life,” Dr. Barnes and colleagues noted.
In contrast with the above statements, the guideline recommends usage of probiotics to prevent recurrent pouchitis in patients with recurrent, antibiotic-responsive pouchitis.
The De Simone formulation of multistrain probiotics is best supported in this scenario, the guideline notes, as this product was used in clinical trials, which collectively showed an 87% reduced risk of relapse over 12 months.
Antibiotics
Although the guideline supports antibiotics for prevention of pouchitis, the panelists noted that only one randomized controlled trial supports this recommendation, and negative effects of long-term usage need to be considered, including promotion of drug-resistant organisms and risk of Clostridioides difficile infection.
Dr. Barnes and colleagues cited more data supporting antibiotics for treatment of pouchitis, and noted that metronidazole and/or ciprofloxacin remain the preferred choices, with a typical duration of 2-4 weeks.
“An approach using a combination of antibiotics may be more effective in patients who do not respond to single-antibiotic therapy,” the panelists wrote, noting that oral vancomycin may also be considered when a patient does not respond to initial therapy.
For patients with recurrent pouchitis that relapses shortly after discontinuing antibiotics, chronic antibiotics should be considered, according to the guideline.
Immunosuppressive therapies
Advanced immunosuppressive therapies are recommended for patients with chronic antibiotic-dependent pouchitis, including those approved for treatment of UC or Crohn’s disease.
“Advanced immunosuppressive therapies may be used in lieu of chronic, continuous antibiotic therapy, particularly in patients who are intolerant to antibiotics or where patients and/or providers are concerned about risks of long-term antibiotic therapy,” the panelists wrote.
For patients with chronic antibiotic-refractory pouchitis, the guideline makes a general recommendation for advanced immunosuppressive therapies while specifically noting that vedolizumab has a greater strength of evidence in this scenario, citing the EARNEST trial.
A separate recommendation for corticosteroids is made for the same patient group, with ileal-release budesonide remaining the preferred formulation. In contrast, mesalamine is not recommended, based on a lack of supporting evidence.
Finally, the panelists recommend using corticosteroids in patients with Crohn’s-like disease of the pouch.
Future directions
“Even though pouchitis is relatively common after IPAA for UC, we observed that most of the evidence informing these guidelines was low to very low quality, derived from case series or small cohort studies, and several knowledge gaps exist,” Dr. Barnes and colleagues wrote. “Several initiatives towards improving management of inflammatory pouch disorders are already underway. However, concerted efforts in key domains are central towards improving patient care.”
They suggested that research should focus on standardizing disease entities, characterizing natural history and risk factors for inflammatory disorders of the pouch, and improving clinical trial design.The guideline was funded by the AGA Institute. The panelists disclosed relationships with Bristol-Myers Squibb, Sandoz, AbbVie, and others.
The American Gastroenterological Association (AGA) has published a new clinical practice guideline on the management of pouchitis and inflammatory pouch disorders.
The guidance document, authored by Edward L. Barnes, MD, of the University of North Carolina at Chapel Hill and colleagues, includes eleven conditional recommendations that steer usage of probiotics, antibiotics, and immunosuppressive therapies in patients with these conditions, which occur most often after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC).
“Multiple strategies have been utilized in the treatment and prevention of pouchitis and inflammatory pouch conditions, including antibiotics, probiotics, corticosteroids, and advanced immunosuppressive therapies including biologics and oral small-molecule drugs,” the guideline panelists wrote on the AGA website. “However, most of the evidence base is primarily derived from retrospective observational studies or comparisons of small cohorts. Data on patients’ values and preferences for specific management decisions and treatment choices are also limited. This results in substantial practice variability.”
Still, the area is advancing. Dr. Barnes and colleagues highlighted new scoring systems for characterizing endoscopic findings and patient-reported outcomes, as well as the recent EARNEST trial (N Engl J Med. 2023 Mar 30;388(13):1191-1200), which compared vedolizumab with placebo in patients with chronic refractory pouchitis, and should be considered a “landmark study in the field,” as it could shape future trial design.
Based on all available evidence and clinical experience, the panelists issued the following recommendations, which were approved by the AGA Governing Board.
Probiotics
Because of a knowledge gap, the guideline makes no recommendation for or against use of probiotics for either the primary prevention or treatment of pouchitis.
They offered a similar explanation for the lack of guidance on using probiotics to treat pouchitis, and noted that antibiotics have demonstrated effectiveness where probiotics have not, making them the preferred treatment choice.
“There is potential that delaying therapy or using probiotics when they are not as effective as antibiotics may have significant impact on an individual patient’s quality of life,” Dr. Barnes and colleagues noted.
In contrast with the above statements, the guideline recommends usage of probiotics to prevent recurrent pouchitis in patients with recurrent, antibiotic-responsive pouchitis.
The De Simone formulation of multistrain probiotics is best supported in this scenario, the guideline notes, as this product was used in clinical trials, which collectively showed an 87% reduced risk of relapse over 12 months.
Antibiotics
Although the guideline supports antibiotics for prevention of pouchitis, the panelists noted that only one randomized controlled trial supports this recommendation, and negative effects of long-term usage need to be considered, including promotion of drug-resistant organisms and risk of Clostridioides difficile infection.
Dr. Barnes and colleagues cited more data supporting antibiotics for treatment of pouchitis, and noted that metronidazole and/or ciprofloxacin remain the preferred choices, with a typical duration of 2-4 weeks.
“An approach using a combination of antibiotics may be more effective in patients who do not respond to single-antibiotic therapy,” the panelists wrote, noting that oral vancomycin may also be considered when a patient does not respond to initial therapy.
For patients with recurrent pouchitis that relapses shortly after discontinuing antibiotics, chronic antibiotics should be considered, according to the guideline.
Immunosuppressive therapies
Advanced immunosuppressive therapies are recommended for patients with chronic antibiotic-dependent pouchitis, including those approved for treatment of UC or Crohn’s disease.
“Advanced immunosuppressive therapies may be used in lieu of chronic, continuous antibiotic therapy, particularly in patients who are intolerant to antibiotics or where patients and/or providers are concerned about risks of long-term antibiotic therapy,” the panelists wrote.
For patients with chronic antibiotic-refractory pouchitis, the guideline makes a general recommendation for advanced immunosuppressive therapies while specifically noting that vedolizumab has a greater strength of evidence in this scenario, citing the EARNEST trial.
A separate recommendation for corticosteroids is made for the same patient group, with ileal-release budesonide remaining the preferred formulation. In contrast, mesalamine is not recommended, based on a lack of supporting evidence.
Finally, the panelists recommend using corticosteroids in patients with Crohn’s-like disease of the pouch.
Future directions
“Even though pouchitis is relatively common after IPAA for UC, we observed that most of the evidence informing these guidelines was low to very low quality, derived from case series or small cohort studies, and several knowledge gaps exist,” Dr. Barnes and colleagues wrote. “Several initiatives towards improving management of inflammatory pouch disorders are already underway. However, concerted efforts in key domains are central towards improving patient care.”
They suggested that research should focus on standardizing disease entities, characterizing natural history and risk factors for inflammatory disorders of the pouch, and improving clinical trial design.The guideline was funded by the AGA Institute. The panelists disclosed relationships with Bristol-Myers Squibb, Sandoz, AbbVie, and others.
FROM THE AMERICAN GASTROENTEROLOGICAL ASSOCIATION
Inflammatory Responses to a Common Food Additive May Depend On the Microbiome
Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
The consumption of highly processed foods, enriched with food additives, is associated with an increased risk of developing inflammatory bowel disease (IBD). Alteration of the intestinal barrier and microbiota encroachment on epithelial cells is thought to be one of the mechanisms leading to inappropriate mucosal immune activation in response to food additive intake. However, we still do not know why some exposed individuals develop IBD while others do not. The findings of Daniel and colleagues suggest that proinflammatory sensitivity to the food additive carboxymethylcellulose (CMC) is primarily dependent on the composition of the gut microbiota, and that this sensitivity can be, at least partially, transferable, using fecal microbiota transfers in a mouse model of IBD. In particular, they identified 11 taxa of the host basal microbiota associated with the development of intestinal inflammation in response to CMC.
Finally, this study also illustrates the relevance of systematically assessing the impact of food additives and emulsifiers on the gut microbiota and intestinal physiology in order to evaluate their safety using translational approaches similar to those applied by Daniel and colleagues.
Nicolas Benech, MD, PhD is an assistant professor at the Lyon 1 University and Gastroenterology department, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France, the director of the Lyon Fecal Microbiota transplantation Center, and cofounder of the Lyon GEM Microbiota Study Group. He has no conflicts.
Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
Inflammatory responses to the food additive carboxymethylcellulose (CMC) may depend on the unique characteristics of an individual’s microbiome, according to recent research.
These findings suggest that CMC, which is commonly used as a thickener and emulsifier to improve texture and shelf life of food, could potentially trigger chronic inflammation in genetically prone individuals, although more work is needed to pinpoint the exact microbiota involved, reported lead author Noëmie Daniel, PhD, of the French National Institute of Health and Medical Research (INSERM), Paris, and colleagues.“Preclinical work has shown that [CMC] consumption detrimentally impacts the intestinal microbiota in a way that promotes chronic inflammation,” the investigators wrote in a research letter in Cellular and Molecular Gastroenterology and Hepatology.
They published the results of a randomized, double-blind controlled trial that showed that the seven individuals exposed to a CMC-supplemented diet had “significant alterations in microbiota composition and metabolome” compared with the nine control subjects.
Yet responses to CMC varied widely. In the treatment group, some participants were relatively insensitive to CMC, while two participants had “stark alterations” in their microbiome.
“Such CMC sensitivity was not associated with overt signs of intestinal inflammation but nonetheless might mark proneness to chronic inflammation, compelling us to better understand mechanisms that mediate CMC sensitivity,” the investigators wrote.
To learn more, Dr. Daniel and colleagues conducted the present study, which involved a series of analyses and experiments.
They first compared inflammatory bowel disease-associated mutations and basal gene expression between CMC-sensitive and CMC-insensitive individuals from their previous trial. Neither were associated with CMC sensitivity, they found.
Evaluating microbiota was a more fruitful approach. Microbiome multivariable association with linear models analysis revealed 11 amplicon sequence variants (ASVs) that differed between groups.
“This algorithm did not detect differences between randomly selected subjects, arguing that ASVs that are associated with CMC sensitivity were not false discoveries but rather had marked, and perhaps contributed to, CMC sensitivity status,” the investigators wrote.
Next, they transplanted pre-CMC fecal samples from 2 CMC-sensitive and 2 CMC-insensitive individuals into germ-free, colitis-prone, interleukin 10-/- mice. Exposing these mice to CMC led to distinct changes in microbiota that was not clearly associated with the sensitivity status of the donor. However, mice that received transplants from CMC-sensitive individuals demonstrated increased microbiota-derived proinflammatory markers, increased microbiota encroachment, and “stark” intestinal inflammation after CMC consumption, suggesting that these responses were somehow mediated by the microbiome.
“These [results] indicate a role for basal microbiotas in influencing CMC impact on this cardinal feature of intestinal inflammation and suspected driver of chronic diseases,” the investigators wrote.
“Our findings suggest that the microbiota participate in the extent to which an individual harbors proneness to CMC-induced inflammatory diseases,” they added. “Accordingly, CMC consumption may be one trigger of chronic inflammation in genetically prone individuals colonized with a given microbial ecosystem.”
Research on a larger number of participants appears needed to substantiate their observations and determine the exact microbiota contributor(s) driving CMC sensitivity, the researchers concluded.
The investigators disclosed no conflicts of interest. Funding support came from a starting grant from the European Research Council under the European Union’s Horizon 2020 research and innovation program, a Chaire d’Excellence from IdEx Université de Paris, an award from the Fondation de l’Avenir, ANR grants EMULBIONT and DREAM, and the national program Microbiote from INSERM (B.C.). Supported also came from National Institutes of Health grants, the Penn Center for Nutritional Science and Medicine, and the Max Planck Society.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
AI Shows Potential for Detecting Mucosal Healing in Ulcerative Colitis
Artificial intelligence (AI) systems show high potential for detecting mucosal healing in ulcerative colitis with optimal diagnostic performance, according to a new systematic review and meta-analysis.
AI algorithms replicated expert opinion with high sensitivity and specificity when evaluating images and videos. At the same time, moderate-high heterogeneity of the data was found, the authors noted.
“Artificial intelligence software is expected to potentially solve the longstanding issue of low-to-moderate interobserver agreement when human endoscopists are required to indicate mucosal healing or different grades of inflammation in ulcerative colitis,” Alessandro Rimondi, lead author and clinical fellow at the Royal Free Hospital and University College London Institute for Liver and Digestive Health, London, England, told this news organization.
“However, high levels of heterogeneity have been found, potentially linked to how differently the AI software was trained and how many cases it has been tested on,” he said. “This partially limits the quality of the body of evidence.”
The study was published online in Digestive and Liver Disease.
Evaluating AI Detection
In clinical practice, assessing mucosal healing in inflammatory bowel disease (IBD) is critical for evaluating a patient’s response to therapy and guiding strategies for treatment, surgery, and endoscopic surveillance. In an era of precision medicine, assessment of mucosal healing should be precise, readily available in an endoscopic report, and highly reproducible, which requires high accuracy and agreement in endoscopic diagnosis, the authors noted.
AI systems — particularly deep learning algorithms based on convolutional neural network architecture — may allow endoscopists to establish an objective and real-time diagnosis of mucosal healing and improve the average quality standards at primary and tertiary care centers, the authors wrote. Research on AI in IBD has looked at potential implications for endoscopy and clinical management, which opens new areas to explore.
Dr. Rimondi and colleagues conducted a systematic review of studies up to December 2022 that involved an AI-based system used to estimate any degree of endoscopic inflammation in IBD, whether ulcerative colitis or Crohn’s disease. After that, they conducted a diagnostic test accuracy meta-analysis restricted to the field in which more than five studies providing diagnostic performance — mucosal healing in ulcerative colitis based on luminal imaging — were available.
The researchers identified 12 studies with luminal imaging in patients with ulcerative colitis. Four evaluated the performance of AI systems on videos, six focused on fixed images, and two looked at both.
Overall, the AI systems achieved a satisfactory performance in evaluating mucosal healing in ulcerative colitis. When evaluating fixed images, the algorithms achieved a sensitivity of 0.91 and specificity of 0.89, with a diagnostic odds ratio (DOR) of 92.42, summary receiver operating characteristic curve (SROC) of 0.957, and area under the curve (AUC) of 0.957. When evaluating videos, the algorithms achieved 0.86 sensitivity, 0.91 specificity, 70.86 DOR, 0.941 SROC, and 0.941 AUC.
“It is exciting to see artificial intelligence expand and be effective for conditions beyond colon polyps,” Seth Gross, MD, professor of medicine and clinical chief of gastroenterology and hepatology at NYU Langone Health, New York, told this news organization.
Dr. Gross, who wasn’t involved with this study, has researched AI applications in endoscopy and colonoscopy. He and colleagues have found that machine learning software can improve lesion and polyp detection, serving as a “second set of eyes” for practitioners.
“Mucosal healing interpretation can be variable amongst providers,” he said. “AI has the potential to help standardize the assessment of mucosal healing in patients with ulcerative colitis.”
Improving AI Training
The authors found moderate-high levels of heterogeneity among the studies, which limited the quality of the evidence. Only 2 of the 12 studies used an external dataset to validate the AI systems, and 1 evaluated the AI system on a mixed database. However, seven used an internal validation dataset separate from the training dataset.
It is crucial to find a shared consensus on training for AI models, with a shared definition of mucosal healing and cutoff thresholds based on recent guidelines, Dr. Rimondi and colleagues noted. Training data ideally should be on the basis of a broad and shared database containing images and videos with high interobserver agreement on the degree of inflammation, they added.
“We probably need a consensus or guidelines that identify the standards for training and testing newly developed software, stating the bare minimum number of images or videos for the training and testing sections,” Dr. Rimondi said.
In addition, due to interobserver misalignment, an expert-validated database could help serve the purpose of a gold standard, he added.
“In my opinion, artificial intelligence tends to better perform when it is required to evaluate a dichotomic outcome (such as polyp detection, which is a yes or no task) than when it is required to replicate more difficult tasks (such as polyp characterization or judging a degree of inflammation), which have a continuous range of expression,” Dr. Rimondi said.
The authors declared no financial support for this study. Dr. Rimondi and Dr. Gross reported no financial disclosures.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) systems show high potential for detecting mucosal healing in ulcerative colitis with optimal diagnostic performance, according to a new systematic review and meta-analysis.
AI algorithms replicated expert opinion with high sensitivity and specificity when evaluating images and videos. At the same time, moderate-high heterogeneity of the data was found, the authors noted.
“Artificial intelligence software is expected to potentially solve the longstanding issue of low-to-moderate interobserver agreement when human endoscopists are required to indicate mucosal healing or different grades of inflammation in ulcerative colitis,” Alessandro Rimondi, lead author and clinical fellow at the Royal Free Hospital and University College London Institute for Liver and Digestive Health, London, England, told this news organization.
“However, high levels of heterogeneity have been found, potentially linked to how differently the AI software was trained and how many cases it has been tested on,” he said. “This partially limits the quality of the body of evidence.”
The study was published online in Digestive and Liver Disease.
Evaluating AI Detection
In clinical practice, assessing mucosal healing in inflammatory bowel disease (IBD) is critical for evaluating a patient’s response to therapy and guiding strategies for treatment, surgery, and endoscopic surveillance. In an era of precision medicine, assessment of mucosal healing should be precise, readily available in an endoscopic report, and highly reproducible, which requires high accuracy and agreement in endoscopic diagnosis, the authors noted.
AI systems — particularly deep learning algorithms based on convolutional neural network architecture — may allow endoscopists to establish an objective and real-time diagnosis of mucosal healing and improve the average quality standards at primary and tertiary care centers, the authors wrote. Research on AI in IBD has looked at potential implications for endoscopy and clinical management, which opens new areas to explore.
Dr. Rimondi and colleagues conducted a systematic review of studies up to December 2022 that involved an AI-based system used to estimate any degree of endoscopic inflammation in IBD, whether ulcerative colitis or Crohn’s disease. After that, they conducted a diagnostic test accuracy meta-analysis restricted to the field in which more than five studies providing diagnostic performance — mucosal healing in ulcerative colitis based on luminal imaging — were available.
The researchers identified 12 studies with luminal imaging in patients with ulcerative colitis. Four evaluated the performance of AI systems on videos, six focused on fixed images, and two looked at both.
Overall, the AI systems achieved a satisfactory performance in evaluating mucosal healing in ulcerative colitis. When evaluating fixed images, the algorithms achieved a sensitivity of 0.91 and specificity of 0.89, with a diagnostic odds ratio (DOR) of 92.42, summary receiver operating characteristic curve (SROC) of 0.957, and area under the curve (AUC) of 0.957. When evaluating videos, the algorithms achieved 0.86 sensitivity, 0.91 specificity, 70.86 DOR, 0.941 SROC, and 0.941 AUC.
“It is exciting to see artificial intelligence expand and be effective for conditions beyond colon polyps,” Seth Gross, MD, professor of medicine and clinical chief of gastroenterology and hepatology at NYU Langone Health, New York, told this news organization.
Dr. Gross, who wasn’t involved with this study, has researched AI applications in endoscopy and colonoscopy. He and colleagues have found that machine learning software can improve lesion and polyp detection, serving as a “second set of eyes” for practitioners.
“Mucosal healing interpretation can be variable amongst providers,” he said. “AI has the potential to help standardize the assessment of mucosal healing in patients with ulcerative colitis.”
Improving AI Training
The authors found moderate-high levels of heterogeneity among the studies, which limited the quality of the evidence. Only 2 of the 12 studies used an external dataset to validate the AI systems, and 1 evaluated the AI system on a mixed database. However, seven used an internal validation dataset separate from the training dataset.
It is crucial to find a shared consensus on training for AI models, with a shared definition of mucosal healing and cutoff thresholds based on recent guidelines, Dr. Rimondi and colleagues noted. Training data ideally should be on the basis of a broad and shared database containing images and videos with high interobserver agreement on the degree of inflammation, they added.
“We probably need a consensus or guidelines that identify the standards for training and testing newly developed software, stating the bare minimum number of images or videos for the training and testing sections,” Dr. Rimondi said.
In addition, due to interobserver misalignment, an expert-validated database could help serve the purpose of a gold standard, he added.
“In my opinion, artificial intelligence tends to better perform when it is required to evaluate a dichotomic outcome (such as polyp detection, which is a yes or no task) than when it is required to replicate more difficult tasks (such as polyp characterization or judging a degree of inflammation), which have a continuous range of expression,” Dr. Rimondi said.
The authors declared no financial support for this study. Dr. Rimondi and Dr. Gross reported no financial disclosures.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) systems show high potential for detecting mucosal healing in ulcerative colitis with optimal diagnostic performance, according to a new systematic review and meta-analysis.
AI algorithms replicated expert opinion with high sensitivity and specificity when evaluating images and videos. At the same time, moderate-high heterogeneity of the data was found, the authors noted.
“Artificial intelligence software is expected to potentially solve the longstanding issue of low-to-moderate interobserver agreement when human endoscopists are required to indicate mucosal healing or different grades of inflammation in ulcerative colitis,” Alessandro Rimondi, lead author and clinical fellow at the Royal Free Hospital and University College London Institute for Liver and Digestive Health, London, England, told this news organization.
“However, high levels of heterogeneity have been found, potentially linked to how differently the AI software was trained and how many cases it has been tested on,” he said. “This partially limits the quality of the body of evidence.”
The study was published online in Digestive and Liver Disease.
Evaluating AI Detection
In clinical practice, assessing mucosal healing in inflammatory bowel disease (IBD) is critical for evaluating a patient’s response to therapy and guiding strategies for treatment, surgery, and endoscopic surveillance. In an era of precision medicine, assessment of mucosal healing should be precise, readily available in an endoscopic report, and highly reproducible, which requires high accuracy and agreement in endoscopic diagnosis, the authors noted.
AI systems — particularly deep learning algorithms based on convolutional neural network architecture — may allow endoscopists to establish an objective and real-time diagnosis of mucosal healing and improve the average quality standards at primary and tertiary care centers, the authors wrote. Research on AI in IBD has looked at potential implications for endoscopy and clinical management, which opens new areas to explore.
Dr. Rimondi and colleagues conducted a systematic review of studies up to December 2022 that involved an AI-based system used to estimate any degree of endoscopic inflammation in IBD, whether ulcerative colitis or Crohn’s disease. After that, they conducted a diagnostic test accuracy meta-analysis restricted to the field in which more than five studies providing diagnostic performance — mucosal healing in ulcerative colitis based on luminal imaging — were available.
The researchers identified 12 studies with luminal imaging in patients with ulcerative colitis. Four evaluated the performance of AI systems on videos, six focused on fixed images, and two looked at both.
Overall, the AI systems achieved a satisfactory performance in evaluating mucosal healing in ulcerative colitis. When evaluating fixed images, the algorithms achieved a sensitivity of 0.91 and specificity of 0.89, with a diagnostic odds ratio (DOR) of 92.42, summary receiver operating characteristic curve (SROC) of 0.957, and area under the curve (AUC) of 0.957. When evaluating videos, the algorithms achieved 0.86 sensitivity, 0.91 specificity, 70.86 DOR, 0.941 SROC, and 0.941 AUC.
“It is exciting to see artificial intelligence expand and be effective for conditions beyond colon polyps,” Seth Gross, MD, professor of medicine and clinical chief of gastroenterology and hepatology at NYU Langone Health, New York, told this news organization.
Dr. Gross, who wasn’t involved with this study, has researched AI applications in endoscopy and colonoscopy. He and colleagues have found that machine learning software can improve lesion and polyp detection, serving as a “second set of eyes” for practitioners.
“Mucosal healing interpretation can be variable amongst providers,” he said. “AI has the potential to help standardize the assessment of mucosal healing in patients with ulcerative colitis.”
Improving AI Training
The authors found moderate-high levels of heterogeneity among the studies, which limited the quality of the evidence. Only 2 of the 12 studies used an external dataset to validate the AI systems, and 1 evaluated the AI system on a mixed database. However, seven used an internal validation dataset separate from the training dataset.
It is crucial to find a shared consensus on training for AI models, with a shared definition of mucosal healing and cutoff thresholds based on recent guidelines, Dr. Rimondi and colleagues noted. Training data ideally should be on the basis of a broad and shared database containing images and videos with high interobserver agreement on the degree of inflammation, they added.
“We probably need a consensus or guidelines that identify the standards for training and testing newly developed software, stating the bare minimum number of images or videos for the training and testing sections,” Dr. Rimondi said.
In addition, due to interobserver misalignment, an expert-validated database could help serve the purpose of a gold standard, he added.
“In my opinion, artificial intelligence tends to better perform when it is required to evaluate a dichotomic outcome (such as polyp detection, which is a yes or no task) than when it is required to replicate more difficult tasks (such as polyp characterization or judging a degree of inflammation), which have a continuous range of expression,” Dr. Rimondi said.
The authors declared no financial support for this study. Dr. Rimondi and Dr. Gross reported no financial disclosures.
A version of this article appeared on Medscape.com.
FROM DIGESTIVE AND LIVER DISEASE
Who Is Helped by AI Use During Colonoscopy?
Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed.
Is it living up to that promise?
It seems that depends on where, how, and by whom it’s being implemented.
Clinical Trials vs the Real World
The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”
Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively).
“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.
A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users).
A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps.
Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.
Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates.
The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice.
A ‘Mishmash’ of Methods
“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged.
Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.
Other real-world studies look at detection by time, Dr. Sharma said.
For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue.
These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.
“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
Perceptions and Expectations
Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.
“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”
Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.
A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates.
However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%).
The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”
“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
Are Less Experienced Endoscopists Helped More?
It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this.
A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.
Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.
But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.
“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.”
Some studies reflect that dual benefit.
The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.
An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).
A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”
Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively.
The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
Improving the Algorithms
Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications.
Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.
“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.
AI can also play a role in health equity, she noted.
“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said.
Looking Ahead
Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.”
Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation.
In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.”
Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed.
Is it living up to that promise?
It seems that depends on where, how, and by whom it’s being implemented.
Clinical Trials vs the Real World
The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”
Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively).
“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.
A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users).
A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps.
Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.
Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates.
The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice.
A ‘Mishmash’ of Methods
“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged.
Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.
Other real-world studies look at detection by time, Dr. Sharma said.
For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue.
These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.
“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
Perceptions and Expectations
Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.
“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”
Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.
A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates.
However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%).
The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”
“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
Are Less Experienced Endoscopists Helped More?
It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this.
A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.
Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.
But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.
“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.”
Some studies reflect that dual benefit.
The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.
An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).
A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”
Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively.
The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
Improving the Algorithms
Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications.
Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.
“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.
AI can also play a role in health equity, she noted.
“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said.
Looking Ahead
Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.”
Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation.
In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.”
Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) holds the promise of identifying premalignant and advanced malignant lesions during colonoscopy that might otherwise be missed.
Is it living up to that promise?
It seems that depends on where, how, and by whom it’s being implemented.
Clinical Trials vs the Real World
The majority of randomized clinical trials of AI use conducted worldwide “clearly show an increase in the adenoma detection rate (ADR) during colonoscopy,” Prateek Sharma, MD, a gastroenterologist at The University of Kansas Cancer Center, Kansas City, told this news. “But the real-world results have been quite varied; some show improvement, and others don’t.”
Dr. Sharma is coauthor of a recent pooled analysis of nine randomized controlled trials on the impact of AI on colonoscopy surveillance after polyp removal. It found that AI use increased the proportion of patients requiring intensive surveillance by approximately 35% in the United States and 20% in Europe (absolute increases of 2.9% and 1.3%, respectively).
“While this may contribute to improved cancer prevention, it significantly adds patient burden and healthcare costs,” the authors concluded.
A recent retrospective analysis of staggered implementation of a computer-aided detection (CADe) system at a single academic center in Chicago found that for screening and surveillance colonoscopy combined, endoscopists using CADe identified more adenomas and serrated polyps — but only endoscopists who used CADe regularly (“majority” users).
A systematic review and meta-analysis of 21 randomized controlled trials comparing CADe with standard colonoscopy found increased detection of adenomas, but not of advanced adenomas, as well as higher rates of unnecessary removal of non-neoplastic polyps.
Adding to the mix, a multicenter randomized controlled trial of patients with a positive fecal immunochemical test found that AI use was not associated with better detection of advanced neoplasias. Lead author Carolina Mangas Sanjuán, MD, PhD, Hospital General Universitario Dr. Balmis, Alicante, Spain, told this news organization the results were “surprising,” given previous studies showing benefit.
Similarly, a pragmatic implementation trial conducted by Stanford, California, researchers showed no significant effect of CADe on ADR, adenomas per colonoscopy, or any other detection metric. Furthermore, CADe had no effect on procedure times or non-neoplastic detection rates.
The authors cautioned against viewing their study as an “outlier,” however, and pointed to an Israeli study comparing adenoma and polyp detection rates 6 months before and after the introduction of AI-aided colonoscopy. Those authors reported no performance improvement with the AI device and concluded that it was not useful in routine practice.
A ‘Mishmash’ of Methods
“It’s not clear why some studies are positive, and some are negative,” Dr. Sharma acknowledged.
Study design is a factor, particularly in real-world studies, he said. Some researchers use the before/after approach, as in the Israeli study; others compare use in different rooms — that is, one with a CADe device and one without. Like the Chicago analysis, findings from such studies probably depend on whether the colonoscopists with the CADe device in the room actually use it.
Other real-world studies look at detection by time, Dr. Sharma said.
For example, a study of 1780 colonoscopies in China found that AI systems showed higher assistance ability among colonoscopies performed later in the day, when adenoma detection rates typically declined, perhaps owing to fatigue.
These authors suggest that AI may have the potential to maintain high quality and homogeneity of colonoscopies and improve endoscopist performance in large screening programs and centers with high workloads.
“There’s a mishmash of different kinds of real-world studies coming in, and it’s very difficult to figure it all out,” Dr. Sharma said. “We just have to look at these devices as innovations and embrace them and work with them to see how it fits it in our practice.”
Perceptions and Expectations
Emerging evidence suggests that endoscopists’ perceptions and expectations may affect assessments of AI’s potential benefits in practice, Dr. Sharma noted.
“Someone might say, ‘I’m a trained physician. Why do I need a machine to help me?’ That can create a situation in which the endoscopist is constantly challenging the device, trying to overrule it or not give it credit.”
Others might perceive that the AI device will definitely help and therefore not look as carefully themselves for adenomas.
A study at The University of Texas MD Anderson Cancer Center in Houston in which activation of the AI system was at the discretion of the endoscopist found that real-time CADe did not improve adenoma detection among endoscopists with high baseline detection rates.
However, despite its availability, AI-assisted colonoscopy was activated in only half of the cases, and multiple concerns were raised by staff and endoscopists in a postprocedural survey. In particular, endoscopists were concerned that the system would result in too many false-positive signals (82.4%), was too distracting (58.8%), and prolonged procedure time (47.1%).
The authors of the Stanford study that found no benefit with CADe in routine practice noted, “Most concerning would be if, inadvertently, CADe use was accompanied by a simultaneous unconscious degradation in the quality of mucosal exposure, possibly due to a false sense of comfort that CADe would ensure a high-quality examination.”
“We’re trying to evaluate some of these interactions between endoscopists and AI devices both pragmatically in practice as well as in clinical trials,” Dr. Sharma said. “Much depends on the context of how you approach and present the devices. We tell physicians that this is an assist device, not something you’re competing against and not something that’s here to replace you. This is something which may make your lives easier, so try it out.”
Are Less Experienced Endoscopists Helped More?
It seems intuitive that less experienced endoscopists would be helped by AI, and indeed, some recent studies confirm this.
A small randomized controlled trial in Japan, presented during the Presidential Plenary at the American Society for Gastrointestinal Endoscopy (ASGE) annual meeting in May 2023, showed that a CADe system was “particularly useful” for beginning endoscopists, who had lower adenoma miss rates with the device vs a white light control device.
Another randomized controlled trial in Japan found that CADe use was associated with an increased overall ADR among endoscopists in training.
But experienced endoscopists probably can benefit as well, noted Jennifer Christie, MD, Division Director, Gastroenterology and Hepatology at the University of Colorado School of Medicine Anschutz Medical Campus in Aurora.
“We know that these AI devices can be useful in training our fellows to detect certain lesions in the colon,” she said. “However, they’re also helpful for many very seasoned practitioners, as an adjunctive tool to help in terms of diagnosis.”
Some studies reflect that dual benefit.
The AID-2 study, designed specifically to look at whether experience had an effect on AI findings during colonoscopy, was conducted among nonexpert endoscopists (lifetime volume of less than 2000 colonoscopies). The researchers, including Dr. Sharma, found that CADe increased the ADR by 22% compared with the control group.
An earlier study, AID-1 , used a similar design but was conducted among experienced endoscopists. In AID-1, the ADR was also significantly higher in the CADe group (54.8%) compared with the control group (40.4%), and adenomas detected per colonoscopy were significantly higher in the CADe group (mean, 1.07) than in the control group (mean, 0.71).
A multivariate post hoc analysis that pooled results from both AID-1 and AID-2 showed that use of CADe and colonoscopy indication, but not the level of examiner experience, were associated with ADR differences. This led the researchers to conclude, “Experience appears to play a minor role as a determining factor for ADR.”
Similarly, a 2023 study from China looked at the mean number of adenomas detected per colonoscopy according to the endoscopist’s experience. All rates were significantly higher in AI-assisted colonoscopies compared with conventional non-AI colonoscopy: overall ADR, 39.9% vs 32.4%; advanced ADR, 6.6% vs 4.9%; ADR of expert endoscopists, 42.3% vs 32.8%; ADR of nonexpert endoscopists, 37.5% vs 32.1%; and adenomas per colonoscopy, 0.59 vs 0.45, respectively.
The authors concluded that “AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists.”
Improving the Algorithms
Experts agree that current and future research will improve the accuracy and quality of AI colonoscopy for all users, leading to new standards and more consistent outcomes in both clinical trials and real-world applications.
Work underway now to improve the algorithms will be an important step in that direction, according to Dr. Christie.
“We need to have enough information to create AI algorithms that allow us to detect early lesions, at least from an imaging standpoint, and we need to improve and increase the sensitivity and the specificity, as well as the predictive value,” she said.
AI can also play a role in health equity, she noted.
“But it’s a double-edged sword, because it depends again on algorithms and machine learning. Perhaps AI can eliminate some of the bias in our clinical decision-making. However, if we don’t train the machine properly with a good, diverse sample of patients and figure out how to integrate some of the social determinants of health that a computer may not otherwise consider, it can create larger disparities and larger biases. AI devices can only be as good and as inclusive as we make them,” Dr. Christie said.
Looking Ahead
Dr. Sharma predicts that “the next slew of studies are going to be on characterization — not just saying there’s an abnormality but distinguishing it further and saying whether the lesion is noncancerous, precancerous, or cancer.”
Other studies will focus on quality improvement of factors, such as withdrawal time and bowel preparation.
In its clinical practice update on AI, the American Gastroenterological Association states, “Eventually, we predict an AI suite of tools for colonoscopy will seem indispensable, as a powerful adjunct to support safe and efficient clinical practice. AI tools that improve colonoscopy quality may become more accepted, and perhaps demanded, by payors, administrators, and possibly even by well-informed patients who want to ensure the highest-quality examination of their colon.”
Dr. Sharma and Dr. Christie disclose no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
Recurrent Bleeding in Small-Intestinal Angiodysplasia Reduced by Thalidomide
, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
, according to results of a new placebo-controlled trial.
At 1 year follow-up, thalidomide doses of 100 mg/day and 50 mg/day outperformed placebo in reducing by at least 50% the number of bleeding episodes, compared with the year prior to treatment, according to the study published online in the New England Journal of Medicine.
SIA, an increasingly recognized cause of repeat obscure gastrointestinal bleeding and iron-deficiency anemia, is a distinct vascular abnormality in the mucosa and submucosa characterized by focal accumulation of ectatic vessels. It is the most common cause of small intestine bleeding, especially among patients older than 50.
There is a high unmet need among patients with SIA for an effective and relatively safe oral medication, given substantial recurrent bleeding risks following endoscopic or surgical procedures, and only observational studies suggest treatment with somatostatin and octreotide, noted senior author Zhizheng Ge, MD, Shanghai Jiao Tong University, Shanghai, China.
SIA is characterized by dilated and tortuous arterial or venous capillaries between thin-walled and immature veins and capillaries without a smooth-muscle layer. Its pathologic process involves chronic hypoxia and vessel sprouting.
Dr. Ge and colleagues postulated that thalidomide’s ability to decrease the expression of proangiogenic factors and angiogenesis would have a long-lasting ameliorating effect on bleeding episodes of angiodysplasia, and thus a continued benefit with respect to bleeding cessation. Their previous small, single-center, open-label, randomized controlled trial of thalidomide for SIA showed a benefit, but it required larger confirmatory trials.
For their current trial, the researchers explored whether a short treatment period, selected to avoid treatment nonadherence, could have a long-term effect. They randomly assigned on a 1:1:1 basis 150 patients with recurrent SIA-related bleeding, defined as at least four episodes during the previous year, to an oral daily dose of 100 mg of thalidomide, 50 mg of thalidomide, or placebo for 4 months.
The patients (median age, 62.2 years; 88% aged 50 years or older) were followed for at least 1 year after treatment. The trial was conducted at 10 sites in China.
The primary endpoint was effective response, defined as a reduction of at least 50% in the number of bleeding episodes in the year following thalidomide treatment, compared with the number in the year before treatment. Bleeding was defined as the presence of overt bleeding or a positive fecal occult blood test.
The percentages of patients with effective response at 1-year follow-up were 68.6% in the 100-mg thalidomide group, 51% in the 50-mg thalidomide group, and 16% in the placebo group.
Among secondary endpoints, the incidence of rebleeding during the 4-month treatment period was 27.5% (14 of 51 patients) in the 100-mg thalidomide group, 42.9% (21 of 49 patients) in the 50-mg thalidomide group, and 90% (45 of 50 patients) in the placebo group. The percentage of patients who received a blood transfusion during the 1-year follow-up period were 17.6% in the 100-mg thalidomide group, 24.5% in the 50-mg thalidomide group, and 62% in the placebo group.
Cessation of bleeding, defined by two consecutive negative fecal occult blood tests on different days, during 1 year of follow-up was observed in 44 patients: 26 (51%) of patients in the 100-mg thalidomide group, 16 (32.7%) in the 50-mg thalidomide group, and 2 (4%) in the placebo group. The authors urge further exploration of the duration of benefit and the efficacy of longer courses of treatment.
Adverse events, all grade 1 or 2, resolved after treatment of symptoms, completion of treatment, or discontinuation of thalidomide or placebo.
Retreatment May Be Necessary
In an accompanying editorial, Loren Laine, MD, chief of the section of digestive diseases, internal medicine, and medical chief, digestive health, Yale School of Medicine, New Haven, Connecticut, affirmed the authors’ conclusions and commended the quality of evidence they provided.
“Their results suggest that thalidomide may be disease-modifying, with efficacy persisting after discontinuation,” wrote Dr. Laine, also a Yale professor of medicine and digestive diseases.
While thalidomide effectively prevented rebleeding for 42 patients during the year after therapy was stopped, suggesting an alteration of angiodysplasias, rebleeding during the subsequent 3-27 months occurred among 20 of those patients, Dr. Laine noted. That finding, “suggests that retreatment will be needed,” although the appropriate duration of treatment before retreatment and the duration of retreatment remain unclear, he added.
The study’s reliance on bleeding episodes that were defined by positive fecal occult blood tests, which may be clinically unimportant, is a weakness in the trial, Dr. Laine wrote.
Despite the study’s positive findings, clinicians may still prefer somatostatin analogues because of their potential for better safety and, with once-monthly injections versus daily thalidomide pills, their likelihood for better adherence, Dr. Laine wrote. “[They] will reserve thalidomide for use in patients who have continued bleeding or side effects with somatostatin analogues,” he added.
Somatostatin is rarely used in the treatment of SIA bleeding in China, where thalidomide is relatively easy to obtain and is being used clinically, Dr. Ge told this news organization in response to Dr. Laine’s editorial. “The clinical application of thalidomide has been taken up in other [Chinese] hospitals that have seen our research,” he added.
Future research may include randomized controlled trials of somatostatin, since Chinese experience with it is so limited, Dr. Ge said. “We would want to compare efficacy, safety, feasibility and cost-effectiveness between somatostatin and thalidomide,” he added.
The study was supported by grants from the National Natural Science Foundation of China and a grant from the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine. The author disclosures can be found with the original article.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE