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Weight Loss Surgery, Obesity Drugs Achieve Similar Results but Have Different Safety Profiles
PHILADELPHIA — according to a meta-analysis comparing the efficacy and safety of the different treatment options.
However, tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP-1 RA), produces comparable weight loss and has a favorable safety profile, reported principal investigator Jena Velji-Ibrahim, MD, MSc, from Prisma Health–Upstate/University of South Carolina School of Medicine in Greenville.
In addition, there was “no significant difference in percentage total body weight loss between tirzepatide when comparing it to one-anastomosis gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she said.
All 11 interventions studied exerted weight loss effects, and side-effect profiles were also deemed largely favorable, particularly for endoscopic interventions, she added.
“When we compare bariatric surgery to bariatric endoscopy, endoscopic sleeve gastroplasty and transpyloric shuttle offer a minimally invasive alternative with good weight loss outcomes and fewer adverse events,” she said.
Velji-Ibrahim presented the findings at the annual meeting of the American College of Gastroenterology (ACG).
Comparing Weight Loss Interventions
Many of the studies comparing weight loss interventions to date have been limited by relatively small sample sizes, observational designs, and inconsistent results. This prompted Velji-Ibrahim and her colleagues to conduct what they believe to be the first-of-its-kind meta-analysis on this topic.
They began by conducting a systematic search of the literature to identify randomized controlled trials (RCTs) that compared the efficacy of Food and Drug Administration–approved bariatric surgeries, bariatric endoscopies, and medications — against each other or with placebo — in adults with a body mass index of 25-45, with or without concurrent type 2 diabetes.
A network meta-analysis was then performed to assess the various interventions’ impact on percentage total weight loss and side-effect profiles. P-scores were calculated to rank the treatments and identify the preferred interventions. The duration of therapy was 52 weeks.
In total, 34 eligible RCTs with 15,660 patients were included. Overall, the RCTs analyzed 11 weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and medications (four studies).
Specifically, the bariatric surgeries included RYGB, laparoscopic sleeve gastrectomy, OAGB, and laparoscopic adjustable gastric banding; bariatric endoscopies included endoscopic sleeve gastroplasty, transpyloric shuttle, and intragastric balloon; and medications included tirzepatide, semaglutide, and liraglutide.
Although all interventions were associated with reductions in percentage total weight loss compared with placebo, RYGB led to the greatest reductions (19.29%) and was ranked as the first preferred treatment (97% probability). It was followed in the rankings by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg.
Tirzepatide 15 mg had a slightly lower percentage total weight loss (15.18%) but a favorable safety profile. There was no significant difference in percentage total weight loss between tirzepatide 15 mg and OAGB (mean difference, 2.97%) or laparoscopic sleeve gastrectomy (mean difference, 0.43%).
There was also no significant difference in percentage total weight loss between semaglutide 2.4 mg, compared with endoscopic sleeve gastroplasty and transpyloric shuttle.
Endoscopic sleeve, transpyloric shuttle, and intragastric balloon all resulted in weight loss > 5%.
When compared with bariatric surgery, “endoscopic interventions had a better side-effect profile, with no increased odds of mortality and intensive care needs,” Velji-Ibrahim said.
When it came to the medications, “the most common side effects were gastrointestinal in nature, which included nausea, vomiting, diarrhea, and constipation,” she said.
Combining, Rather Than Comparing, Therapies
Following the presentation, session co-moderator Shivangi T. Kothari, MD, assistant professor of medicine and associate director of endoscopy at the University of Rochester Medical Center in New York, shared her thoughts of what the future of obesity management research might look like.
It’s not just going to be about percentage total weight loss, she said, but about how well the effect is sustained following the intervention.
And we might move “away from comparing one modality to another” and instead study combination therapies, “which would be ideal,” said Kothari.
This was the focus of another meta-analysis presented at ACG 2024, in which Nihal Ijaz I. Khan, MD, and colleagues compared the efficacy of endoscopic bariatric treatment alone vs its combined use with GLP-1 RAs.
The researchers identified three retrospective studies with 266 patients, of whom 143 underwent endoscopic bariatric treatment alone (either endoscopic sleeve gastroplasty or intragastric balloon) and 123 had it combined with GLP-1 RAs, specifically liraglutide.
They reported that superior absolute weight loss was achieved in the group of patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment. The standardized mean difference in body weight loss at treatment follow-up was 0.61 (P <.01).
“Further studies are required to evaluate the safety and adverse events comparing these two treatment modalities and to discover differences between comparing the two endoscopic options to various GLP-1 receptor agonists,” Khan noted.
Neither study had specific funding. Velji-Ibrahim and Khan reported no relevant financial relationships. Kothari reported serving as a consultant for Boston Scientific and Olympus, as well as serving as an advisory committee/board member for Castle Biosciences.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a meta-analysis comparing the efficacy and safety of the different treatment options.
However, tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP-1 RA), produces comparable weight loss and has a favorable safety profile, reported principal investigator Jena Velji-Ibrahim, MD, MSc, from Prisma Health–Upstate/University of South Carolina School of Medicine in Greenville.
In addition, there was “no significant difference in percentage total body weight loss between tirzepatide when comparing it to one-anastomosis gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she said.
All 11 interventions studied exerted weight loss effects, and side-effect profiles were also deemed largely favorable, particularly for endoscopic interventions, she added.
“When we compare bariatric surgery to bariatric endoscopy, endoscopic sleeve gastroplasty and transpyloric shuttle offer a minimally invasive alternative with good weight loss outcomes and fewer adverse events,” she said.
Velji-Ibrahim presented the findings at the annual meeting of the American College of Gastroenterology (ACG).
Comparing Weight Loss Interventions
Many of the studies comparing weight loss interventions to date have been limited by relatively small sample sizes, observational designs, and inconsistent results. This prompted Velji-Ibrahim and her colleagues to conduct what they believe to be the first-of-its-kind meta-analysis on this topic.
They began by conducting a systematic search of the literature to identify randomized controlled trials (RCTs) that compared the efficacy of Food and Drug Administration–approved bariatric surgeries, bariatric endoscopies, and medications — against each other or with placebo — in adults with a body mass index of 25-45, with or without concurrent type 2 diabetes.
A network meta-analysis was then performed to assess the various interventions’ impact on percentage total weight loss and side-effect profiles. P-scores were calculated to rank the treatments and identify the preferred interventions. The duration of therapy was 52 weeks.
In total, 34 eligible RCTs with 15,660 patients were included. Overall, the RCTs analyzed 11 weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and medications (four studies).
Specifically, the bariatric surgeries included RYGB, laparoscopic sleeve gastrectomy, OAGB, and laparoscopic adjustable gastric banding; bariatric endoscopies included endoscopic sleeve gastroplasty, transpyloric shuttle, and intragastric balloon; and medications included tirzepatide, semaglutide, and liraglutide.
Although all interventions were associated with reductions in percentage total weight loss compared with placebo, RYGB led to the greatest reductions (19.29%) and was ranked as the first preferred treatment (97% probability). It was followed in the rankings by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg.
Tirzepatide 15 mg had a slightly lower percentage total weight loss (15.18%) but a favorable safety profile. There was no significant difference in percentage total weight loss between tirzepatide 15 mg and OAGB (mean difference, 2.97%) or laparoscopic sleeve gastrectomy (mean difference, 0.43%).
There was also no significant difference in percentage total weight loss between semaglutide 2.4 mg, compared with endoscopic sleeve gastroplasty and transpyloric shuttle.
Endoscopic sleeve, transpyloric shuttle, and intragastric balloon all resulted in weight loss > 5%.
When compared with bariatric surgery, “endoscopic interventions had a better side-effect profile, with no increased odds of mortality and intensive care needs,” Velji-Ibrahim said.
When it came to the medications, “the most common side effects were gastrointestinal in nature, which included nausea, vomiting, diarrhea, and constipation,” she said.
Combining, Rather Than Comparing, Therapies
Following the presentation, session co-moderator Shivangi T. Kothari, MD, assistant professor of medicine and associate director of endoscopy at the University of Rochester Medical Center in New York, shared her thoughts of what the future of obesity management research might look like.
It’s not just going to be about percentage total weight loss, she said, but about how well the effect is sustained following the intervention.
And we might move “away from comparing one modality to another” and instead study combination therapies, “which would be ideal,” said Kothari.
This was the focus of another meta-analysis presented at ACG 2024, in which Nihal Ijaz I. Khan, MD, and colleagues compared the efficacy of endoscopic bariatric treatment alone vs its combined use with GLP-1 RAs.
The researchers identified three retrospective studies with 266 patients, of whom 143 underwent endoscopic bariatric treatment alone (either endoscopic sleeve gastroplasty or intragastric balloon) and 123 had it combined with GLP-1 RAs, specifically liraglutide.
They reported that superior absolute weight loss was achieved in the group of patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment. The standardized mean difference in body weight loss at treatment follow-up was 0.61 (P <.01).
“Further studies are required to evaluate the safety and adverse events comparing these two treatment modalities and to discover differences between comparing the two endoscopic options to various GLP-1 receptor agonists,” Khan noted.
Neither study had specific funding. Velji-Ibrahim and Khan reported no relevant financial relationships. Kothari reported serving as a consultant for Boston Scientific and Olympus, as well as serving as an advisory committee/board member for Castle Biosciences.
A version of this article first appeared on Medscape.com.
PHILADELPHIA — according to a meta-analysis comparing the efficacy and safety of the different treatment options.
However, tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP-1 RA), produces comparable weight loss and has a favorable safety profile, reported principal investigator Jena Velji-Ibrahim, MD, MSc, from Prisma Health–Upstate/University of South Carolina School of Medicine in Greenville.
In addition, there was “no significant difference in percentage total body weight loss between tirzepatide when comparing it to one-anastomosis gastric bypass (OAGB), as well as laparoscopic sleeve gastrectomy,” she said.
All 11 interventions studied exerted weight loss effects, and side-effect profiles were also deemed largely favorable, particularly for endoscopic interventions, she added.
“When we compare bariatric surgery to bariatric endoscopy, endoscopic sleeve gastroplasty and transpyloric shuttle offer a minimally invasive alternative with good weight loss outcomes and fewer adverse events,” she said.
Velji-Ibrahim presented the findings at the annual meeting of the American College of Gastroenterology (ACG).
Comparing Weight Loss Interventions
Many of the studies comparing weight loss interventions to date have been limited by relatively small sample sizes, observational designs, and inconsistent results. This prompted Velji-Ibrahim and her colleagues to conduct what they believe to be the first-of-its-kind meta-analysis on this topic.
They began by conducting a systematic search of the literature to identify randomized controlled trials (RCTs) that compared the efficacy of Food and Drug Administration–approved bariatric surgeries, bariatric endoscopies, and medications — against each other or with placebo — in adults with a body mass index of 25-45, with or without concurrent type 2 diabetes.
A network meta-analysis was then performed to assess the various interventions’ impact on percentage total weight loss and side-effect profiles. P-scores were calculated to rank the treatments and identify the preferred interventions. The duration of therapy was 52 weeks.
In total, 34 eligible RCTs with 15,660 patients were included. Overall, the RCTs analyzed 11 weight loss treatments, including bariatric surgeries (four studies), bariatric endoscopies (three studies), and medications (four studies).
Specifically, the bariatric surgeries included RYGB, laparoscopic sleeve gastrectomy, OAGB, and laparoscopic adjustable gastric banding; bariatric endoscopies included endoscopic sleeve gastroplasty, transpyloric shuttle, and intragastric balloon; and medications included tirzepatide, semaglutide, and liraglutide.
Although all interventions were associated with reductions in percentage total weight loss compared with placebo, RYGB led to the greatest reductions (19.29%) and was ranked as the first preferred treatment (97% probability). It was followed in the rankings by OAGB, tirzepatide 15 mg, laparoscopic sleeve gastrectomy, and semaglutide 2.4 mg.
Tirzepatide 15 mg had a slightly lower percentage total weight loss (15.18%) but a favorable safety profile. There was no significant difference in percentage total weight loss between tirzepatide 15 mg and OAGB (mean difference, 2.97%) or laparoscopic sleeve gastrectomy (mean difference, 0.43%).
There was also no significant difference in percentage total weight loss between semaglutide 2.4 mg, compared with endoscopic sleeve gastroplasty and transpyloric shuttle.
Endoscopic sleeve, transpyloric shuttle, and intragastric balloon all resulted in weight loss > 5%.
When compared with bariatric surgery, “endoscopic interventions had a better side-effect profile, with no increased odds of mortality and intensive care needs,” Velji-Ibrahim said.
When it came to the medications, “the most common side effects were gastrointestinal in nature, which included nausea, vomiting, diarrhea, and constipation,” she said.
Combining, Rather Than Comparing, Therapies
Following the presentation, session co-moderator Shivangi T. Kothari, MD, assistant professor of medicine and associate director of endoscopy at the University of Rochester Medical Center in New York, shared her thoughts of what the future of obesity management research might look like.
It’s not just going to be about percentage total weight loss, she said, but about how well the effect is sustained following the intervention.
And we might move “away from comparing one modality to another” and instead study combination therapies, “which would be ideal,” said Kothari.
This was the focus of another meta-analysis presented at ACG 2024, in which Nihal Ijaz I. Khan, MD, and colleagues compared the efficacy of endoscopic bariatric treatment alone vs its combined use with GLP-1 RAs.
The researchers identified three retrospective studies with 266 patients, of whom 143 underwent endoscopic bariatric treatment alone (either endoscopic sleeve gastroplasty or intragastric balloon) and 123 had it combined with GLP-1 RAs, specifically liraglutide.
They reported that superior absolute weight loss was achieved in the group of patients receiving GLP-1 RAs in combination with endoscopic bariatric treatment. The standardized mean difference in body weight loss at treatment follow-up was 0.61 (P <.01).
“Further studies are required to evaluate the safety and adverse events comparing these two treatment modalities and to discover differences between comparing the two endoscopic options to various GLP-1 receptor agonists,” Khan noted.
Neither study had specific funding. Velji-Ibrahim and Khan reported no relevant financial relationships. Kothari reported serving as a consultant for Boston Scientific and Olympus, as well as serving as an advisory committee/board member for Castle Biosciences.
A version of this article first appeared on Medscape.com.
FROM ACG 2024
Low-Volume Bowel Prep Easier, as Effective as Standard Prep in Hospitalized Patients
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).
Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.
“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.
Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.
“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.
In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.
After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.
In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.
Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.
Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.
In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
Ease of Use Is a Plus
On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”
In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).
“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.
“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”
Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.
“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”
The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM ACG 2024
Breath Gas Patterns Predict Response to Low FODMAP Diet
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
PHILADELPHIA — , according to a new study.
The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”
Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”
He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens.
Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.
Breaths That Can Predict Response
To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale.
Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.
Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.
Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet.
The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day.
Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.
The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
A Potential New Biomarker
Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit.
There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.”
Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness.
“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role.
Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.
A version of this article appeared on Medscape.com.
FROM ACG 2024
GLP-1 RAs Reduce Early-Onset CRC Risk in Patients With Type 2 Diabetes
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
PHILADELPHIA — according to the results of a retrospective study.
“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.
The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.
Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.
The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
Retrospective Database Analysis
Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.
They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.
Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).
Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
A Proposed Protective Effect
Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.
“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”
This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”
These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.
“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”
Hypothesis-Generating Results
Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research.
"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News.
She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D.
Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said.
“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained.
Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention."
The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.
A version of this article appeared on Medscape.com.
FROM ACG 2024
AI Tool Helps Detect, Differentiate Pancreatic Lesions During Endoscopic Ultrasound
PHILADELPHIA —
This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.
Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.
Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.
EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.
With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.
They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.
The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.
For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
Real-Time Validation Next
“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.
This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.
The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.
“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.
Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.
“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.
“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.
“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.
The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.
Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.
Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.
EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.
With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.
They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.
The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.
For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
Real-Time Validation Next
“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.
This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.
The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.
“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.
Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.
“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.
“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.
“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.
The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.
Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.
Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.
EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.
With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.
They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.
The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.
For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
Real-Time Validation Next
“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.
This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.
The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.
“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.
Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.
“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.
“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.
“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.
The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.
A version of this article appeared on Medscape.com.
FROM ACG 2024
FIT Completion and Yield Similar in Younger and Older Adults
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
, a new study has found.
The study also found a similar low 3% rate of CRC detected at colonoscopy in both the younger and older adults.
“Our study suggests that adults ages 45-49 have a colorectal cancer risk that is similar to what we see in adults age 50,” senior author Jeffrey K. Lee, MD, MPH, gastroenterologist and research scientist at Kaiser Permanente Northern California Division of Research (DOR) in Oakland, California, said in a news release.
“The low number of cancers we found also provides support for initially offering younger adults a non-invasive test, like FIT, to determine which patients would benefit from a colonoscopy,” Lee noted.
Timely and Important Question
“This study addresses a timely and important clinical question, namely, is FIT an acceptable screening modality in patients aged 45-49,” Ziad F. Gellad, MD, MPH, AGAF, professor of medicine, Duke University Medical Center, Durham, North Carolina, who was not involved in the study, said in an interview.
“The finding that FIT completion and yield in younger patients is similar to those aged 50 and above is good news because it supports the use of this screening modality in the younger cohort,” said Gellad, section chief, gastroenterology, Durham VA Health Care System.
The study was published online in Annals of Internal Medicine.
In 2021, the US Preventive Services Task Force lowered the age to start CRC screening from 50 to 45 years, in response to studies showing an increased rate of CRC in adults aged 45-49 years.
The decision to start CRC screening at age 45 was made based on modeling studies, which are dependent on assumptions, co-first author Theodore R. Levin, MD, who is also a gastroenterologist and research scientist at Kaiser Permanente DOR, said in an interview.
“We thought it was important to collect real-world data on the experience of screening in this age group. We had no basis to know whether younger people would take up screening or if the yield of screening would be sufficiently high to warrant starting screening in this age group,” said Levin.
The researchers compared FIT screening completion and outcomes in 213,928 patients aged 45-49 years and 53,804 patients aged 50 years who received a FIT kit for the first time. The patients were from Kaiser Permanente Northern California, Washington, and Colorado.
Overall, FIT completion rates were slightly higher in the younger adults than in the 50-year-olds (38.9% vs 37.5%; adjusted risk ratio [aRR], 1.05), although the younger patients from Colorado were substantially less apt to complete a FIT (30.7% vs 40.2%; aRR, 0.77).
In the overall 45- to 49-year age group, 3.6% of adults had a positive FIT result, only slightly lower than the 4% positivity rate in the 50-year age group (aRR, 0.91).
About two thirds of adults in both groups who had a positive FIT result went on to have a colonoscopy within 3 months of receiving the test result.
Adenoma detection during colonoscopy was slightly lower in the younger than in the older group (58.8% vs 67.7%; aRR, 0.88). However, yields were similar for adenoma with advanced histology (13.2% vs 15.9%; aRR, 0.86), polyp with high-grade dysplasia (3.4% vs 5.1%; aRR, 0.68), sessile serrated lesion (10.3% vs 11.7%; aRR, 0.92), and CRC (2.8% vs 2.7%; aRR, 1.10).
FIT First Fits With Younger Adults’ Busy Lives
“Overall, people under 50 have lower incidence of cancer than people in their 50s, 60s, and 70s. However, if you do a test like FIT first, you can improve the yield of colonoscopy, which is a much more efficient strategy,” Levin said.
He noted that younger people are the least likely to be screened.
“They are busy with work and family responsibilities and may not realize that they are at risk for CRC. It is important to offer them a test that is easy to perform and does not require them to miss a day of work or arrange for a driver. They should be offered an option to screen with a stool-based test as an easy way to fit CRC screening into their busy lives,” Levin said.
Gellad said the study also highlights the limitations of FIT, “namely, that the low uptake and suboptimal colonoscopy follow-up of positive tests, also extend into the lower age group.”
Additionally, Gellad said he hopes other large systems will replicate this study to address the generalizability of these findings outside the Kaiser system.
The study was funded by the Kaiser Permanente Sydney R. Garfield Memorial Fund. Disclosures for study authors are available with the original article. Gellad consulted for Merck & Co. and Novo Nordisk and is a co-founder of Higgs Boson, Inc.
A version of this article appeared on Medscape.com.
Ultraprocessed Foods Associated With Relapse Risk in Crohn’s Disease
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
VIENNA —
Certain subgroups of UPFs, specifically bread, pastries, and starch as well as oil and spreads, exhibited the strongest association with relapse risks of approximately threefold.
“In addition to treating active inflammatory bowel disease (IBD), we want to maintain remission for the long term,” Chen Sarbagili Shabat, PhD, clinical dietitian from Tel Aviv Medical Center in Israel, said in an interview. “It’s highly important. We know environmental factors are associated with the disease, which is why we can treat active disease with diet. Likewise, we can manage CD in a remission state with diet.”
This is the first prospective study of this particular level of UPFs in people with Crohn’s disease who are in remission, noted Shabat, who presented the findings at United European Gastroenterology (UEG) Week 2024.
Previously, a meta-analysis of prospective cohort studies showed that a diet high in UPFs is associated with a 70% increased risk for development of CD, and a longitudinal study showed that “Western” dietary patterns were associated with relapse risk in patients with IBD, Shabat reported.
Effect of High vs Low Intake of UPFs
The current single-center, prospective cohort study, followed 111 patients with CD every 3 months until relapse for up to 1 year.
Participants were aged 18-75 years (mean age, 38 years), with a median disease duration of 8.7 years. They were required to have maintained steroid-free clinical remission (Harvey-Bradshaw Index (HBI), < 5) for 3 months or more. The median duration of clinical remission at recruitment was 3 years.
Data collection included HBI level, medication type and dosage to ensure constant therapy and full compliance, and a stool sample for fecal calprotectin measurement.
The primary outcome comprised a clinical relapse HBI ≥ 5 over the 12-month follow-up or a change in disease activity requiring a change in medication, hospitalization, or any IBD-related surgery.
Participants were asked to complete a processed food questionnaire to assess the intake of UPFs and a food frequency questionnaire to assess the total intake of energy, macronutrients, and micronutrients. UPFs were divided into high and low intakes using a median cutoff of 3.6 servings/day.
The low intake group included 57 participants, and the high intake group included 54.
A total of 24 patients (21.6%) experienced a clinical relapse event, 7 in the low intake group vs 17 in the high intake group (hazard ratio [HR], 3.86; 95% CI, 1.30-11.47; P = .015 after adjustments).
In a subset of 97 patients with baseline fecal calprotectin measurements, 6 (n = 50) in the low intake group experienced a clinical relapse vs 15 (n = 47) in the high intake group (HR, 4.32; 95% CI, 1.36-13.73; P = .013 after adjustments).
Fecal calprotectin results were also suggestive of an association between high intake of UPFs and gut inflammation, Shabat reported.
Food Groups and Emulsifiers
UPFs were divided into subgroups: Bread, pastries, and starch; oils and spreads; ultraprocessed meat; sweet products and desserts; and ultraprocessed beverages.
The highest associations with relapse were in the subgroup of bread, pastries, and starch (HR, 3.37; 95% CI, 1.26-8.25) and the subgroup of oils and spreads (HR, 2.76; 95% CI, 1.02-7.45).
“The selection of healthy food is highly important, especially since we know that certain food ingredients can contribute to the pathogenesis of CD,” Shabat said. Patients can use partial enteral nutrition to provide 40%-50% of daily caloric intake in order to maintain remission, but she acknowledged it can be really difficult to adhere to.
She concluded by asserting that the study results, along with future research, should contribute to establishing nutritional guidelines to reduce UPF consumption in patients with CD in order to maintain remission.
Commenting on the study, Kevin Whelan, PhD, professor of dietetics and head of the Department of Nutritional Sciences at King’s College London in England, said that he was intrigued by the subgroup analysis that showed breads, pastries, oils, and spreads as having the strongest association with relapse risk.
He also remarked that these foods almost ubiquitously contain emulsifiers, and so the association might have less to do with UPFs in general and more to do with emulsifiers.
Concurring, Shabat noted that, while emulsifiers can negatively influence the microbiota and the gut barrier function, as well as contribute to intestinal inflammation, further mechanistic studies are required to understand these effects.
We need to determine if all additives have the same effect on the inflammatory process and also need studies looking at UPFs alone, she added.
Shabat reported receiving personal fees from Nestle Health Science (Wolfson Medical Center IP) for consulting and speaking and from Takeda and Ferring for speaking. Whelan reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM UEG 2024
Cendakimab That Targets IL-13 Shows Promise in Eosinophilic Esophagitis
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
VIENNA — , according to interim results of a pivotal phase 3 trial.
Treatment with cendakimab also improved key endoscopic and histologic features, even in patients who had an inadequate response or intolerance to steroids, reported Alain Schoepfer, MD, gastroenterologist from Centre Hospitalier Universitaire Vaudois and University of Lausanne, in Switzerland.
The drug was generally safe and well tolerated up to 24 weeks of treatment, added Schoepfer, who presented the results during a presentation at the United European Gastroenterology (UEG) Week 2024.
Targeting IL-13 Shows ‘Surprisingly Good Results’
EoE is a chronic, progressive, immune-mediated, inflammatory disease that is mainly driven by the cytokine, IL-13.
In a prior phase 2 study, cendakimab, which selectively binds to IL-13 and blocks its interaction with both the IL-13Ra1 and the IL-13Ra2 receptors, was shown to improve symptoms and endoscopic features of EoE.
For the current phase 3 trial, participants were required to have a peak eosinophil count (PEC) of ≥ 15 eosinophils (eos)/high power field (hpf) and 4 or more days of dysphagia over the 2 weeks prior to the start of the study. In addition, they had to have shown a complete lack of response to proton pump inhibitor (PPI) treatment for 8 weeks or more.
A total of 430 patients were randomized 1:1:1 to subcutaneous cendakimab (360 mg) once weekly for 48 weeks; subcutaneous cendakimab (360 mg) once weekly for 24 weeks, then once every 2 weeks for a further 24 weeks; or subcutaneous placebo once weekly for 48 weeks.
Patient characteristics were similar across randomization groups. The majority of participants were men, with a mean age of 35 years (range, 12-75 years); adolescents comprised 6%-11% of the total. The disease duration was around 5-6 years for all participants, of which 45% were on a stable PPI dosage and around 65% had steroid intolerance or an inadequate response. The endoscopic reference score was around 10 across all groups. The mean PEC was around 160 eos/hpf in the cendakimab arms vs 200 eos/hpf in the placebo arm.
Schoepfer reported results for the coprimary endpoints — the mean change from baseline in dysphagia days and the proportion of patients with eosinophil histologic response (PEC ≤ 6 eos/hpf) — at week 24. At this point, a total of 286 patients had received treatment with 360 mg of cendakimab once weekly, and 143 had received placebo.
The change in dysphagia days was −6.1 in patients on cendakimab once weekly vs −4.2 in patients on placebo (P = .0005). The proportion of patients with eosinophil histologic response was 28.6% in the treatment arm vs 2.2% in the placebo arm.
The results were similar for patients who were classified as having had a steroid inadequate response. The change in dysphagia days was −6.3 in the cendakimab group vs −4.7 in the placebo group (P = .0156). The eosinophil histologic response was 29.5% in the treatment group vs 2.1% in the placebo group (P < .0001).
Endoscopic response, a key secondary endpoint, showed a change from baseline to week 24 in the endoscopic features of EoE. The total endoscopic reference scores were −5.2 for patients on cendakimab once weekly and −1.2 for patients on placebo (P < .0001).
The safety profile of cendakimab was “unspectacular,” Schoepfer said, with adverse events related to the study drug occurring in 30% of patients in the treatment arm vs 18.9% of those in the placebo arm. He noted that as the trial was conducted during the COVID pandemic, there were some infections.
Serious adverse events, which were assessed by investigators to not be related to the study drug, occurred in 1.8% and 2.8% of patients on cendakimab and placebo, respectively. Drug discontinuation occurred in 1.4% in the cendakimab group and 0.7% in the placebo group. There were no deaths.
“We really need drugs for this disease, given that there are very few alternatives to steroids and PPIs,” Co-moderator Ram Dickman, MD, Division of Gastroenterology, Rabin Medical Center, Petah Tikva, Israel, said in an interview.
Right now, we have dupilumab, which targets two receptors: IL-4 and IL-13. But targeting IL-13 by itself “is showing surprisingly good results,” so cendakimab is a good candidate to be in “the first line of biologic treatments,” Dickman said.
“It’s safe and works rapidly,” he added. “Given this is a phase 3 study, I believe we’ll see it on the market.”
Schoepfer has served as a consultant for Regeneron/Sanofi, Adare/Ellodi, AbbVie, AstraZeneca, Celgene/Receptos/Bristol Myers Squibb, Dr. Falk Pharma, Gossamer Bio, GSK, Janssen, MSD, Pfizer, Regeneron/Sanofi, Takeda, and Vifor; received grant/research support from Adare/Ellodi, Celgene/Receptos/Bristol Myers Squibb, GSK, and Regeneron/Sanofi. Dickman has declared no relevant disclosures.
A version of this article appeared on Medscape.com.
FROM UEG 2024
New mRNA Vaccine May Shield Against C difficile Infections
A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical study, published in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitis, toxic megacolon), can be fatal.
An Increasingly Pressing Issue
C difficile is the leading cause of infectious diarrhea acquired in healthcare settings.
A 2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
The Vaccine Candidate
Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).
Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.
Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.
To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.
Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.
In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical study, published in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitis, toxic megacolon), can be fatal.
An Increasingly Pressing Issue
C difficile is the leading cause of infectious diarrhea acquired in healthcare settings.
A 2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
The Vaccine Candidate
Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).
Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.
Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.
To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.
Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.
In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
A group of researchers from the University of Pennsylvania, Philadelphia, has developed a messenger RNA (mRNA) vaccine, delivered via lipid nanoparticles (LNPs) — the same type as the COVID-19 vaccine produced by Moderna and Pfizer — targeting Clostridioides difficile (formerly Clostridium difficile). According to the authors, the results of their preclinical study, published in Science, demonstrated this technology as a promising platform for C difficile vaccine development and could be the starting point for curbing intestinal infections that, in their most severe forms (pseudomembranous colitis, toxic megacolon), can be fatal.
An Increasingly Pressing Issue
C difficile is the leading cause of infectious diarrhea acquired in healthcare settings.
A 2019 study reported a global incidence of C difficile infections at 2.2 per 1000 hospital admissions per year and 3.5 per 10,000 patient-days per year.
The Vaccine Candidate
Vaccine candidates tested so far have used toxoids or recombinant proteins targeting the combined repetitive oligopeptide (CROP) or receptor-binding domain (RBD) of the two primary C difficile toxins, TcdA and TcdB. The US researchers are now exploring the mRNA-LNP vaccine approach to target multiple antigens simultaneously. They developed a bivalent vaccine (including the CROP and RBD domains of both toxins) and a trivalent vaccine (with an additional virulence factor, the metalloprotease Pro-Pro endopeptidase-1).
Mice vaccinated with the bivalent and trivalent vaccines produced immunoglobulin G antibody titers two to four times higher than those elicited by recombinant protein with an adjuvant. The vaccination stimulated the proliferation of follicular T helper cells and the antigen-specific response of B lymphocytes, laying the foundation for a strong and long-lasting humoral response. The vaccines were also immunogenic in hamsters.
Vaccinated mice not only survived a toxin dose five times higher than the 100% lethal dose but also demonstrated the vaccine’s protective effect through serum transfer; unvaccinated mice given serum from vaccinated mice survived the lethal challenge. More importantly, when exposed to a lethal dose of the bacterium itself, all vaccinated mice survived.
To demonstrate the vaccine’s efficacy in patients with a history of C difficile infection and high recurrence risk — ideal candidates for vaccination — the researchers vaccinated mice that had previously survived a sublethal infection. Six months after the initial infection and vaccination, these mice remained protected against mortality when reexposed to the bacterium.
Additionally, a quadrivalent vaccine that included an immunogen targeting C difficile spores — key agents in transmission — also proved effective. Low levels of bacteria and toxins in the feces of mice vaccinated in this way suggested that spore vaccination could limit initial colonization.
In tests with nonhuman primates, two doses of the vaccines targeting either the vegetative form or the spores elicited strong immune responses against bacterial toxins and virulence factors. Human trials may indeed be on the horizon.
This story was translated from Univadis Italy using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Myth of the Month: Are Thickened Liquids Helpful in Dysphagia Patients?
Case: An 80-year-old man with advanced Alzheimer’s disease is admitted to the hospital after a fall. He is noted to have coughing spells after drinking liquids. He has a swallowing study done which shows severe slowing of motility in the esophagus.
What do you recommend?
A. Feeding tube
B. Thickened liquids
C. Continue current diet
The correct answer for this patient is to allow them to continue their current diet. They do not need thickened liquids. A feeding tube would not be recommended.1
So are there any data supporting the widespread use of thickened liquid diets for patients with dysphagia and aspiration?
Multiple clinical guidelines for stroke recommend the use of thickened liquids despite minimal to no evidence of efficacy.2 It is a common practice to give patients with advanced dementia thickened liquids, especially in the hospital setting. Does this help?
Makhnevich and colleagues published a cohort study of Alzheimer’s disease patients with dysphagia admitted to the hospital over a 5-year period.3 Almost half of the cohort received a thickened liquid diet; these patients were matched with patients who received a thin liquid diet. There was no significant difference in hospital mortality between the groups that received thick liquids and thin liquids (hazard ratio, 0.92; P = .46). Patients receiving thickened liquids were less likely to be intubated but were more likely to have pulmonary infections.
A 2018 Cochrane review concluded that there was no consensus on immediate and long-term effects of modifying the consistency of fluid for swallowing difficulties in dementia because too few studies have been completed.4 So why is this important information or lack of information?
What is so bad about a thickened liquid diet?
Eric Widera, MD, shared in JAMA Internal Medicine his experience along with his hospice and palliative care team of drinking thickened liquids.5 He drank only thickened liquids for a 12-hour period. “The challenge was eye-opening. It was the first time I experienced the terrible taste and texture of thickened liquids,” he wrote. He shared some of the risks of thickened liquids: dehydration, poor oral intake, and decreased quality of life.
The bottom line is that there is scant evidence for the benefit of thickened liquids, especially for patients with advanced dementia and dysphagia, and giving thickened liquids is not a benign intervention, because of poor tolerability of the diet.
References
1. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.
2. McCurtin A et al. J Eval Clin Pract. 2020;26:1744-60.
3. Makhnevich A et al. JAMA Intern Med. 2024 Jul 1;184(7):778-85.
4. Flynn E et al. Cochrane Database Syst Rev. 2018 Sep 24;9(9):CD011077.
5. Widera E. JAMA Intern Med. 2024 Jul 1;184(7):786-7.
Case: An 80-year-old man with advanced Alzheimer’s disease is admitted to the hospital after a fall. He is noted to have coughing spells after drinking liquids. He has a swallowing study done which shows severe slowing of motility in the esophagus.
What do you recommend?
A. Feeding tube
B. Thickened liquids
C. Continue current diet
The correct answer for this patient is to allow them to continue their current diet. They do not need thickened liquids. A feeding tube would not be recommended.1
So are there any data supporting the widespread use of thickened liquid diets for patients with dysphagia and aspiration?
Multiple clinical guidelines for stroke recommend the use of thickened liquids despite minimal to no evidence of efficacy.2 It is a common practice to give patients with advanced dementia thickened liquids, especially in the hospital setting. Does this help?
Makhnevich and colleagues published a cohort study of Alzheimer’s disease patients with dysphagia admitted to the hospital over a 5-year period.3 Almost half of the cohort received a thickened liquid diet; these patients were matched with patients who received a thin liquid diet. There was no significant difference in hospital mortality between the groups that received thick liquids and thin liquids (hazard ratio, 0.92; P = .46). Patients receiving thickened liquids were less likely to be intubated but were more likely to have pulmonary infections.
A 2018 Cochrane review concluded that there was no consensus on immediate and long-term effects of modifying the consistency of fluid for swallowing difficulties in dementia because too few studies have been completed.4 So why is this important information or lack of information?
What is so bad about a thickened liquid diet?
Eric Widera, MD, shared in JAMA Internal Medicine his experience along with his hospice and palliative care team of drinking thickened liquids.5 He drank only thickened liquids for a 12-hour period. “The challenge was eye-opening. It was the first time I experienced the terrible taste and texture of thickened liquids,” he wrote. He shared some of the risks of thickened liquids: dehydration, poor oral intake, and decreased quality of life.
The bottom line is that there is scant evidence for the benefit of thickened liquids, especially for patients with advanced dementia and dysphagia, and giving thickened liquids is not a benign intervention, because of poor tolerability of the diet.
References
1. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.
2. McCurtin A et al. J Eval Clin Pract. 2020;26:1744-60.
3. Makhnevich A et al. JAMA Intern Med. 2024 Jul 1;184(7):778-85.
4. Flynn E et al. Cochrane Database Syst Rev. 2018 Sep 24;9(9):CD011077.
5. Widera E. JAMA Intern Med. 2024 Jul 1;184(7):786-7.
Case: An 80-year-old man with advanced Alzheimer’s disease is admitted to the hospital after a fall. He is noted to have coughing spells after drinking liquids. He has a swallowing study done which shows severe slowing of motility in the esophagus.
What do you recommend?
A. Feeding tube
B. Thickened liquids
C. Continue current diet
The correct answer for this patient is to allow them to continue their current diet. They do not need thickened liquids. A feeding tube would not be recommended.1
So are there any data supporting the widespread use of thickened liquid diets for patients with dysphagia and aspiration?
Multiple clinical guidelines for stroke recommend the use of thickened liquids despite minimal to no evidence of efficacy.2 It is a common practice to give patients with advanced dementia thickened liquids, especially in the hospital setting. Does this help?
Makhnevich and colleagues published a cohort study of Alzheimer’s disease patients with dysphagia admitted to the hospital over a 5-year period.3 Almost half of the cohort received a thickened liquid diet; these patients were matched with patients who received a thin liquid diet. There was no significant difference in hospital mortality between the groups that received thick liquids and thin liquids (hazard ratio, 0.92; P = .46). Patients receiving thickened liquids were less likely to be intubated but were more likely to have pulmonary infections.
A 2018 Cochrane review concluded that there was no consensus on immediate and long-term effects of modifying the consistency of fluid for swallowing difficulties in dementia because too few studies have been completed.4 So why is this important information or lack of information?
What is so bad about a thickened liquid diet?
Eric Widera, MD, shared in JAMA Internal Medicine his experience along with his hospice and palliative care team of drinking thickened liquids.5 He drank only thickened liquids for a 12-hour period. “The challenge was eye-opening. It was the first time I experienced the terrible taste and texture of thickened liquids,” he wrote. He shared some of the risks of thickened liquids: dehydration, poor oral intake, and decreased quality of life.
The bottom line is that there is scant evidence for the benefit of thickened liquids, especially for patients with advanced dementia and dysphagia, and giving thickened liquids is not a benign intervention, because of poor tolerability of the diet.
References
1. American Geriatrics Society Ethics Committee and Clinical Practice and Models of Care Committee. J Am Geriatr Soc. 2014;62(8):1590-3.
2. McCurtin A et al. J Eval Clin Pract. 2020;26:1744-60.
3. Makhnevich A et al. JAMA Intern Med. 2024 Jul 1;184(7):778-85.
4. Flynn E et al. Cochrane Database Syst Rev. 2018 Sep 24;9(9):CD011077.
5. Widera E. JAMA Intern Med. 2024 Jul 1;184(7):786-7.