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Etrasimod Appears Effective in Eosinophilic Esophagitis: Phase 2 Study
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
Etrasimod, an investigational, oral selective sphingosine-1-phosphate (S1P)–receptor modulator, also improved endoscopic features of EoE, overall symptom severity, and dysphagia in some patients, researchers reported.
“These results support further investigation of etrasimod in EoE,” said Evan S. Dellon, MD, MPH, AGAF, of the University of North Carolina at Chapel Hill.
Dr. Dellon presented the results from the phase 2 study at the October 2023 annual scientific meeting of the American College of Gastroenterology in Vancouver, Canada.
VOYAGE Study
In the VOYAGE study, 108 adults were included, with about half female and an average EoE diagnosis for nearly 5 years.
The patients were randomized to once-daily doses of etrasimod 2 mg, etrasimod 1 mg, or placebo for 24 weeks, followed by a 28-week still-ongoing extension period investigating the efficacy and safety of daily oral etrasimod 1 mg and 2 mg, compared with placebo.
After 24 weeks of treatment, there was a 52.4% reduction in peak eosinophil count (PEC) in the group of patients who were given a 2-mg daily dose of etrasimod compared to placebo, Dr. Dellon said.
Among patients given a 1-mg daily dose of etrasimod, there was a 27.4% reduction in PEC.
Meanwhile, there was a 61% increase in PEC for people who were given placebo.
Etrasimod also bested placebo on secondary outcomes in the VOYAGE study, including:
- Comprehensive histologic severity and extent scores, with a change of -0.2 in both etrasimod groups (P < .0001), compared with a slight increase for the placebo group.
- Endoscopic features (EREFS), with a decline of 1.3 for the 2-mg–dose etrasimod group (P = .0303), compared with a slight decline for the placebo group. There was a decline of 1.0 in the 1-mg–dose etrasimod group, but this was not statistically significant.
Higher Dose Arm, Better Results
In the email exchange with GI & Hepatology News, Dr. Dellon said this appears to be “a dose-response where the 2-mg dose is needed to see more prominent response, but the EREFS response is in the right direction with the 1-mg dose.”
The study found a statistically significant decrease in only one segment of the trial participants, those who took the 2-mg dose and had a history of dilation, as measured by the Dysphagia Symptom Questionnaire (DSQ). In that group, there was a reported decrease of 21.6 points from baseline.
“The average scores at baseline are in the low 30s. The range for DSQ (which is a composite score of daily measurements over 14 days) is from 0 to 84,” Dr. Dellon wrote. “A score in the 30s over 2 weeks is quite symptomatic, so a decrease of 21.6 points is substantial.”
Dr. Dellon and co-authors said etrasimod appeared to be well tolerated with a safety profile consistent with use of the drug in patients with ulcerative colitis.
In treatment-emergent adverse events, elevation of liver transaminases was reported among 4 of 39 patients (10.3%) in the 1-mg etrasimod group and 3 of the 41 patients (7.3%) in the 2-mg etrasimod group, compared with none in the placebo group.
Bilirubin elevation was reported in 2 patients (5.1%) in the 1-mg etrasimod group and none in the 2-mg etrasimod or placebo groups.
Prospect of Another EoE Treatment
In an interview with GI & Hepatology News, Scott Gabbard, MD, a gastroenterologist at Cleveland Clinic, said, “For so many years, there was no FDA approved therapy [for EoE]. Now, we do have an FDA approved therapy.”
The FDA approved the first treatment for EoE — dupilumab (Dupixent) — last year.
“It’s exciting to suddenly have the prospect of more options for patients with EoE. We can see multiple other options for our patients who sorely need therapy coming down the pipeline,” Dr. Gabbard said.
The data support further investigation, with only about one potential concern drawing attention during the presentation, he added.
“Overall, there were no serious adverse events,” Dr. Gabbard said. “There was clearly a change in baseline and overall symptom scores.”
In an email exchange with GI & Hepatology News, Jennifer Horsley-Silva, MD, of the Mayo Clinic, said the VOYAGE study was important because it serves as a proof of concept that targeting S1P receptors can affect EoE.
“A limitation of the study is it was conducted in a specific group of patients with EoE: a substantial number were refractory to corticosteroids, and over half had prior esophageal dilations,” she wrote.
Pfizer sponsored the VOYAGE trial. Dr. Dellon indicated no relevant financial relationships. Dr. Horsley Silva has research funding from Regeneron/Sanofi, Allakos, Celgene, Bristol Myers Squibb, and has participated in an advisory board for Sanofi Genzyme. No disclosures were included for Dr. Gabbard and no recent paper is available in PubMed for Dr. Horsley-Silva.
FROM ACG 2023
Ultrasound Monitoring of IBD May Prompt Faster Treatment Change
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
, according to a small retrospective analysis.
“Current disease monitoring tools have significant limitations,” said Noa Krugliak Cleveland, MD, director of the intestinal ultrasound program at the University of Chicago. “Intestinal ultrasound is an innovative technology that enables point-of-care assessment.”
Dr. Cleveland presented the findings at the October 2023 American College of Gastroenterology’s annual scientific meeting in Vancouver, Canada.
The analysis was based on 30 patients with IBD in an ongoing real-world prospective study of upadacitinib (Rinvoq, Abbvie) who were not in clinical remission at week 8. For 11 patients, routine clinical care included IUS; the other 19 patients were monitored using a conventional approach.
In the study, both groups were almost evenly split in terms of diagnosis. In the IUS group, four patients had Crohn’s disease and five had ulcerative colitis. In the conventional management group, six had Crohn’s disease and five had ulcerative colitis.
The primary endpoint was time to treatment change.
For the secondary endpoint, the researchers defined clinical remission as a Simple Clinical Colitis Activity Index ≤ 2, or Harvey-Bradshaw Index ≤ 4, and by IUS as bowel wall thickness ≤ 3 mm in the colon or terminal ileum and no hyperemia by color Doppler signal.
The average time to treatment change in the IUS group was 1.1 days, compared with 16.6 days for the conventional management group, Dr. Cleveland reported.
The average time to clinical remission was 26.8 days for the IUS group, compared with 55.3 days for the conventional management group.
The delays in treatment change in the conventional management group were attributed to awaiting test results and endoscopy procedures, as well as communications among clinical team members.
Strength of this research project included its prospective data collection and the experienced sonographers who participated, Dr. Cleveland and colleagues said. Limitations included retrospective analysis, a small number of patients on a single therapy, and the potential for bias in patient selection. Studies of other therapies and a prospective trial are underway.
During the presentation, Dr. Cleveland commented about what kinds of treatment changes were made for patients in the study. They commonly involved extending the induction time, and, in some cases, patients were switched to another treatment, she said.
In an interview, Michael Dolinger, MD, of the Icahn School of Medicine at Mount Sinai in New York, said more research needs to be done to show whether IUS will improve outcomes.
“They’re showing that they make more changes sooner,” he said. “Does that actually affect and improve outcomes? That’s the big question.”
Dr. Dolinger said the concept for using IUS is that it helps physicians catch disease flares earlier and respond faster with changes to the treatment plan, thus preventing the buildup of chronic bowel damage.
“That’s the concept, but that concept is actually not so proven in reality” yet, he said. “But I do believe that they’re on the right path.”
In Dr. Dolinger’s view, adding ultrasound provides a more patient-centric approach to care of people with IBD. With more traditional approaches, patients often are waiting for results of tests done outside of the visit, such as MRI.
“With ultrasound, I am walking them through the results as it’s happening in real time during the clinic visit,” Dr. Dolinger said. ”I am showing them on the screen, allowing them to ask questions. They’re telling me about their symptoms, as I’m putting the probe on where it may hurt, as I’m showing them inflammation or healing. And that changes the whole conversation.”
The study received support from the Mutchnik Family Foundation. Dr. Cleveland reported financial relationships with Bristol Myers Squibb, Neurologica, and Takeda. Her coauthors reported financial relationships with multiple drug and device makers. Dr. Dolinger said he is a consultant for Samsung’s Neurologica Corp., which makes ultrasound equipment.
FROM ACG 2023
Tenapanor Shows Response in IBS-C Within Weeks: Pooled Data Analysis
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
FROM ACG 2023
Pregnant women with eosinophilic esophagitis show no ill effects from inhaled steroids
, according to new research presented at the annual meeting of the American College of Gastroenterology.
“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”
In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.
The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.
Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.
Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)
Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.
“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.
Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
Pregnant patients can maintain EoE management
“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”
The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.
The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.
However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.
The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.
, according to new research presented at the annual meeting of the American College of Gastroenterology.
“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”
In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.
The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.
Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.
Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)
Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.
“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.
Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
Pregnant patients can maintain EoE management
“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”
The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.
The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.
However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.
The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.
, according to new research presented at the annual meeting of the American College of Gastroenterology.
“Currently, there are no specific recommendations about the safe use of steroids in pregnant women with eosinophilic esophagitis (EoE), Julton Tomanguillo Chumbe, MD, said in an interview. “Our recommendations about the use of steroids among this population are based on the safety data extrapolated mainly from pregnant women with asthma.”
In the study, Dr. Chumbe, an internal medicine resident at Charleston Area Medical Center, West Virginia University, Charleston, and colleagues identified pregnant patients aged 18 years and older with a diagnosis of EoE between January 2011 and December 2022 through the TriNetx Global Collaborative Network, which includes 101 health care organizations in 14 countries. The study population consisted of 1,263 individuals.
The researchers used propensity score matching (PSM) to compare the rates of spontaneous abortion, placenta previa, preeclampsia, premature delivery, HELLP syndrome, eclampsia, hyperemesis gravidarum, and major congenital abnormalities between women with EoE who did and did not use steroids during pregnancy. The PSM cohorts included 268 women in each group.
Overall, pregnant women who used steroids were not significantly more likely than were those who did not use steroids to experience spontaneous abortion (3.73% vs. 4.85%, P = .52). Rates of placenta previa, preeclampsia, premature delivery, HELLP syndrome, and hyperemesis gravidarum were equal between the groups (3.73% vs. 3.73%, P = 1.00 for all). No cases of eclampsia occurred in the steroid group, compared with a 3.73% rate in women who did not use steroids.
Incidence of major congenital abnormalities including but not limited to malformations of the eye, ear, face, neck, skull and face bones, and of the circulatory, respiratory, and digestive systems, were similar between the steroid and no steroid groups (7.09% vs. 8.20%, P = .62)
Dr. Chumbe said he was not surprised by the findings, given the robust data about the safe use of steroids in pregnant women with asthma, in terms of pregnancy outcomes and fetal outcomes.
“The findings of this study provide reassurance that the use of steroids in pregnant patients with eosinophilic esophagitis is not significantly associated with an increased risk of worse maternal or fetal outcomes,” he said. “During pregnancy, some patients may discontinue treatment due to safety concerns. However, this study suggests that this may not be necessary.” Consequently, patients can maintain EoE management while reducing the risk of complications.
Looking ahead, “it will be important to have some data about the safe use of dupilumab during pregnancy in patients with eosinophilic esophagitis,” he said.
Pregnant patients can maintain EoE management
“This study is able to address an important concern that many patients have regarding the safety of steroid therapy for EoE, particularly during pregnancy,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and executive vice chair of internal medicine at the University of Cincinnati. “As EoE impacts over 40% of women, most who are in childbearing age, it is important to review the safety of treatment and management of EoE so a mother does not have to choose between EoE management and pregnancy.”
The results from this study were certainly reassuring, though not surprising, Dr. Afzali said. “Previously, the safety profile of steroids during pregnancy was mostly extrapolated from asthma, and other diseases such as inflammatory bowel disease. The results from this study confirm that there are no significant associations with adverse maternal or birth outcomes among women with EoE treated with steroids during pregnancy,” she said.
The study has some limitations, including the retrospective design and potential for selection bias, Dr. Afzali noted. “Further research is needed for the evaluation of newer therapies in the pipeline for treatment of EoE and its safety profile with pregnancy,” she said.
However, “sharing this information in clinical practice “will allow our patients to feel comfortable with continuation of appropriate steroid therapy for treatment and management of their EoE, without having to choose between family planning or pregnancy and EoE care management,” Dr. Afzali said.
The study received no outside funding. Dr. Chumbe an Dr. Afzali indicated having no relevant financial conflicts to disclose.
FROM ACG 2023
Prognostic tool identifies alcohol relapse risk after liver transplant
, based on data from 140 individuals.
Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.
Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.
The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.
The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.
Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.
The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.
The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”
The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.
“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.
The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.
, based on data from 140 individuals.
Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.
Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.
The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.
The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.
Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.
The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.
The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”
The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.
“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.
The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.
, based on data from 140 individuals.
Alcohol relapse after liver transplant ranges from 4% to as high as 95% among patients with alcoholic liver disease (ALD) and better tools are needed to identify those at increased risk, Jiten P. Kothadia, MD, of the University of Tennessee Health Science Center, Memphis, said in a presentation given in October at the annual meeting of the American College of Gastroenterology.
Dr. Kothadia and colleagues evaluated the effectiveness of the Social Determinant Acuity Tool (S-DAT), which stratified patients in terms of successful post-liver transplant outcomes from excellent (S-DAT scores 0-6) to poor candidates (scores 35-40). The S-DAT categories included cognitive function, mental health, social support, coping skills, financial status, compliance, alcohol abuse, substance abuse, reliability, legal issues, understanding the transplant process, and desire for transplant.
The study population included 140 adults with alcoholic liver disease who underwent a liver transplant between January 2016 and November 2021 at a single center. Before surgery, all patients underwent a thorough psychosocial evaluation using the S-DAT. The mean age of the participants was 53.4 years, 107 were male, and 67.9% had abstained from alcohol for more than 6 months prior to transplant.
The primary outcome of post-liver transplant alcohol relapse was defined as any alcohol use regardless of the amount or frequency, based on patient interviews or blood or urine tests.
Overall, the rate of relapse was 23.6%; and the rate within a year was 18.6%. In a multivariate analysis, S-DAT score was a significant predictor of relapse (odds ratio [OR] 1.65, P = .000). Other independent predictors of relapse were post-LT alcohol treatment (OR 7.11, P = .02), smoking history (OR 0.15, P = .03), and marital status (OR 60.28, P = .000). The area under the receiver operative curves (AUROC) for the S-DAT score to predict alcohol relapse within 1 year after LT was 0.77.
The sensitivity of the S-DAT for predicting relapse risk was 96.2%, and specificity was 40.4%; positive and negative predictive values were 26.9% and 97.9%, respectively.
The high sensitivity and negative predictive values of the S-DAT make it a useful screening tool for identifying patients at low risk of alcohol relapse after a liver transplant, Dr. Kothadia said in an interview. “Our score will guide risk-based interventions post-LT to reduce post-LT relapse and improve long-term outcomes.”
The findings included only data from a single center, which may limit generalizability, Dr. Kothadia said. The tool is not yet clinically available, he noted.
“We would like to perform external validation of our S-DAT score as it stresses the importance of these psychosocial variables,” and to confirm the findings in larger, multicenter, prospective clinical trials, he said.
The study received no outside funding. Dr. Kothadia indicated no relevant financial relationships.
FROM ACG 2023
Two novel choices for resection defect repair show similar success
shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.
In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.
In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.
Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.
In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.
The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.
Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).
Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm2 was significantly lower for DAT compared to TSD ($1.0/mm2 vs. $1.6/mm2; P = .002).
Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.
In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm2/min vs. 153.5 mm2/min; P = .003).
“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
Data may inform device decisions
“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.
“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.
“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.
“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”
In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”
The study was limited by the small size and use of data from a single center.
However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.
Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.
The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.
shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.
In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.
In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.
Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.
In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.
The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.
Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).
Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm2 was significantly lower for DAT compared to TSD ($1.0/mm2 vs. $1.6/mm2; P = .002).
Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.
In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm2/min vs. 153.5 mm2/min; P = .003).
“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
Data may inform device decisions
“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.
“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.
“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.
“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”
In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”
The study was limited by the small size and use of data from a single center.
However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.
Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.
The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.
shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
“We know from previous data that defect closure is beneficial, and reduces complications such as delayed bleeding and delayed perforation,” said Salmaan A. Jawaid, MD, of Baylor College of Medicine, Houston, in a presentation at the meeting.
In the past, defect closure was relatively straightforward; however, “the characteristics of these defects are evolving,” and defects are increasing in size, complexity, and number of locations, he said.
In response, management of resection defects has shifted from a one-step closure to a two-step process with approximation of the widest mucosal edges first, followed by complete resection bed closure, Dr. Jawaid said.
Two novel through the scope (TTS) tissue approximation devices used for the closure of large endoscopic resection defects – the dual-action tissue clip (DAT) and the TTS tack/suture device (TSD) – have not been directly compared on the basis of efficacy and cost, he said.
In the current study, Dr. Jawaid and colleagues randomized 56 adults undergoing tissue approximation and defect closure after endoscopic resection to DAT (31 patients) or TSD (25 patients). The patients were treated at a single center between August 2022 and May 2023 for closures of endoscopic resection defects including gastric, duodenum, and colon lesions greater than 20 mm wide and greater than 30 mm long.
The primary outcomes were technical success of tissue approximation and tissue approximation costs. Secondary outcomes were technical success of complete closure, closure costs, and speed of approximation and closure, as well as safety outcomes. Tissue approximation was defined as less than 15 mm of visible resection bed at the widest margin, and complete closure was defined as no visible resection bed.
Tissue approximation rates were not significantly different between the TSD and DAT groups (88% vs. 83.9%, P = .92). However, approximation cost was significantly lower for DAT compared to TSD ($673.1 vs. $973.6; P = .002).
Similarly, complete closure rates were not significantly different between the TSD and DAT groups (92% vs. 93.5%, P = .83), but closure cost/mm2 was significantly lower for DAT compared to TSD ($1.0/mm2 vs. $1.6/mm2; P = .002).
Notably, the three DAT failures (60%) underwent successful tissue approximation with TSD, and the single TSD failure (33%) underwent successful tissue approximation using DAT.
In terms of speed, the averages for both tissue approximation time and closure speed were significantly faster in the DAT group, compared with the TSD group (12.2 minutes vs. 4 minutes, P < .0001; 72.7 mm2/min vs. 153.5 mm2/min; P = .003).
“The DAT clip was three times faster than the TSD,” Dr. Jawaid said in his presentation. Adverse events including device-related events, post–electrocautery syndrome, and delayed bleeding were similarly low with both devices. However, the DAT can be less effective in some circumstances, such as a closed space or difficult location. In the cases of duodenal defects, TSD was able to approximate all, but DAT was unable to approximate any. Reasons for DAT clip failure in these cases included the resection bed being too large and tissue tearing upon grasping. In the TSD group, the presence of looping was associated with failures for cecum and colon defects.
Data may inform device decisions
“This was an important study conducted to evaluate the different scope devices for defect closure,” said Anita Afzali, MD, MPH, AGAF, a gastroenterologist specializing in inflammatory bowel disease and is executive vice chair of internal medicine at the University of Cincinnati.
“These devices have an impact on risk for delayed bleeding and perforation,” said Dr. Afzali, who served as moderator of the session in which the study was presented.
“With different items now available for defect closure, this randomized controlled study provides guidance on which TTS approximation device should be considered, and help determine effectiveness of defect closure,” she said.
“The results of this randomized controlled trial were very informative,” Dr. Afzali said. The data indicated that both DAT and TSD achieved similar rates of tissue approximation and complete closure, but “what was interesting was that one TSD is equivalent to two DAT for tissue approximation. Further, tissue approximation was three times faster with DAT, and complete closure costs were lower in the DAT-treated group.”
In clinical practice, “the study was able to help identify scenarios, such as resection beds involving greater than 50% circumference or defects located in the duodenum, where TSD is preferred over DAT for defect closure. These suggested scenarios are also important for clinical practice and device considerations,” Dr. Afzali said. “Additional studies with use of both devices, TSD and DAT simultaneously on a defect site may be needed to further assist endoscopists in defect management.”
The study was limited by the small size and use of data from a single center.
However, “based on our interim data, both devices are equally effective for tissue approximation of large endoscopic defects,” and facilitate complete defect closure, Dr. Jawaid said.
Ultimately, “both devices have a role,” with DAT being faster and likely more cost effective, while TSD is likely preferable for defects in the duodenum and those with a circumference greater than 50%, he said.
The study received no outside funding. Dr. Jawaid disclosed a consultancy with Boston Scientific, ConMed, CREO Speedboat, and DiLumen. Dr. Afzali disclosed numerous relationships with pharma including having served as an advisor/consultant for AbbVie, Bristol Myers Squibb/Celgene, Eli Lilly, and Gilead, among others.
FROM ACG 2023
Low-dose aspirin provokes no flares in patients with IBD during pregnancy
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
, shows new research presented in October at the American College of Gastroenterology (ACG) Annual Scientific Meeting.
Low-dose aspirin is recommended for pregnant women who are at risk of hypertensive disorders, such as eclampsia, preeclampsia, and gestational diabetes, said Uma Mahadevan, MD, AGAF, a gastroenterologist and director of the University of California, San Francisco Colitis and Crohn’s Disease Center, who presented the research at the meeting. Regular nonsteroidal anti-inflammatory drug use has been associated with increased disease activity in patients with inflammatory bowel disease (IBD), but the impact of low-dose aspirin on IBD during pregnancy has not been well studied, she said.
The study, which was conducted between January 2013 and December 2022 at a single clinic, included 325 women (mean age 34 years) with IBD who had at least one pregnancy. Of these, 53% had ulcerative colitis and 47% had Crohn’s disease. The primary outcome was IBD flare during pregnancy or within 6 months postpartum. Flares were defined as an IBD-related hospitalization and/or surgery, new initiation of IBD therapy, elevated level of fecal calprotectin greater than 150 micrograms per milligram, or new active endoscopic disease.
A total of 95 patients (29%) used low-dose aspirin during pregnancy; 59 took 81 mg and 36 took 162 mg. The cumulative flare rate was similar between patients who took low-dose aspirin and those who did not (24% vs. 26%, P = .83). However, patients who took low-dose aspirin were significantly more likely than were those who did not to experience preterm birth, younger gestational age at delivery, and cesarean delivery (22.1% vs. 6.1%, 38 weeks vs. 39 weeks, 51% vs. 27%, respectively, P < .01 for all).
Overall rates of hypertensive disorders of pregnancy were similar between the low-dose aspirin and non–low-dose aspirin groups (22% vs. 19%, respectively, P = .59), but individuals on low-dose aspirin were more likely to experience preeclampsia than were those not on low-dose aspirin (11.6% vs 4.3%, P = .03).
The study findings support the benefits of aspirin for pregnant women at increased risk for these conditions. “Pregnant patients with IBD should be offered low-dose aspirin without concern for increased risk of flares,” Dr. Mahadevan said.
“This is a very practical study with high relevance in our everyday management of IBD patients,” Shannon Chang, MD, a specialist in IBD with NYU Langone Health, said in an interview. “Having this study helps us understand the risk of increased IBD activity in the setting of aspirin use during pregnancy.”
Dr. Chang was not surprised by the findings. “Since the [ACOG] guidelines changed several years ago, there have been more and more patients with IBD who have taken aspirin during their pregnancies and the results of this study seem to match what we see in clinical practice,” she said. “This study will help us counsel our patients on the safety of aspirin use during pregnancy, and the findings will also be useful for discussions with our obstetrics colleagues who may seek guidance on the safety of aspirin [use] in our pregnant IBD patients.”
The study received no outside funding. Dr. Mahadevan disclosed relationships with AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Eli Lilly, Gilead, Janssen, Pfizer, Prometheus Biosciences, Protagonist Therapeutics, Rani Therapeutics, Roivant, and Takeda. Dr. Chang disclosed serving as a consultant for Pfizer, AbbVie, and BMS.
FROM ACG 2023
Dupilumab promising for children aged 1-11 with EoE
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
VANCOUVER –
High exposure to dupilumab was associated with significantly improved histologic, endoscopic, and transcriptomic improvements, compared with placebo at week 16. Sustained response or improvements continued to week 52 with continued treatment in the high-exposure dupilumab group. Children in the high-exposure dupilumab group also gained more weight during the study than those initially assigned to placebo.
“Eosinophilic esophagitis is a chronic, aggressive, type 2 inflammatory disease that has a substantial impact on quality of life,” said Mirna Chehade, MD, MPH, of the Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai in New York. And the incidence and prevalence of the disease is increasing.
Dupilumab is already indicated for treating EoE in adolescents aged 12 or older as well as adults, but “there are no approved treatments for EoE in children under 12,” said Dr. Chehade, who presented the results of the late-breaking abstract at the ACG: American College of Gastroenterology 2023 annual scientific meeting.
She and her colleagues randomly assigned 102 children aged 1-11 years with active EoE to three groups for the first 16 weeks of the study: 37 to high-exposure dupilumab; 31 to low-exposure dupilumab; and 34 others to placebo, followed by either high- or low-dose dupilumab. Baseline demographics and disease characteristics were comparable between groups.
During an active 36-week extension period, the 37 participants who were initially assigned to receive high-exposure dupilumab continued the same treatment up to week 52. A total of 29 participants initially assigned to receive low-exposure dupilumab continues their regimen as well. Those initially assigned to receive placebo switched to a preassigned active treatment group; 18 children started to take high-exposure dupilumab, and 14 began to take low-exposure dupilumab.
The children in the study had a high burden of disease, as reflected by the duration of EoE as well as histologic, endoscopic, and clinical scores. The mean age was 7.2 years in the placebo group and 6.8 years in the dupilumab group. They were mostly White boys, Dr. Chehade said.
Key outcomes
At week 16, the high-exposure dupilumab group met the primary study endpoint with a peak esophageal intraepithelial eosinophil count ≤ 6 on high-power field assessment. This was significantly different from the placebo group (least squares mean difference, 64.5; 95% confidence interval, 48.19-80.85; P < .0001).
At week 52, 63% of children who remained on high-exposure dupilumab and 53% of those who switched from placebo to high-exposure dupilumab achieved a peak eosinophil count ≤ 6.
The study included multiple secondary outcomes. For example, at week 16, the following measures improved from baseline with high-exposure dupilumab, compared with placebo:
- EoE-Histologic Scoring System grade and stage scores (–0.88 and –0.84 vs. +0.02 and +0.05; both P < .0001).
- EoE-Endoscopic Reference Score (–3.5 vs. +0.3; P < .0001).
- Change in body weight for age percentile (+3.09 vs. +0.29).
- Numeric improvement in caregiver-reported proportion of days experiencing one or more EoE sign (–0.28 vs. –0.17).
At week 52, these outcomes were sustained or improved with continued high-exposure dupilumab. The researchers also saw improvements among the placebo recipients who switched to high-exposure dupilumab.
The reason the children were randomly assigned to high-exposure or low-exposure groups instead of high-dose and low-dose cohorts is because the children grew during the study, Dr. Chehade explained. “As you can see, there was a nice change in weight, and at specific time periods the doses were adjusted to match.”
‘Good safety profile’
Dupilumab was well tolerated. “The safety profile is very similar to what has been so far described and published for dupilumab in adults,” said Dr. Chehade. At week 16, adverse events that were more frequent with dupilumab vs. placebo included COVID-19, rash, headache, and injection-site erythema, for example. Similar safety results were seen up to week 52.
“I think it’s promising as we wait for the actual study to be published,” said Asmeen Bhatt, MD, PhD, co-moderator of the session and assistant professor of medicine at University of Texas Health Science Center, Houston. “The drug was recently approved for adult EOE use, just last year, and it has been shown to be effective.”
“There are a lot of adult drugs that are now being tested in the pediatric population, and this is one of them,” Dr. Bhatt added. “It has a very good safety profile. I’m not a pediatric gastroenterologist but I expect that it will have a lot of utility.”
The study was funded by Regeneron and Sanofi. Dr. Chehade is a consultant for Sanofi and Regeneron and receives research funding from Regeneron. Dr. Bhatt had no relevant financial disclosures.
A version of this article first appeared on Medscape.com.
AT ACG 2023
SGLT2 inhibitors in type 2 diabetes linked to lower risk of developing GI cancers
VANCOUVER –
The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.
On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.
Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.
Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).
All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.
In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
Key findings
Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).
Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.
SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.
The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).
The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.
Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.
Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
‘Eye-opening’ study
“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.
Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”
He added, “I think we need more long-term studies.”
The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER –
The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.
On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.
Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.
Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).
All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.
In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
Key findings
Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).
Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.
SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.
The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).
The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.
Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.
Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
‘Eye-opening’ study
“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.
Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”
He added, “I think we need more long-term studies.”
The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
VANCOUVER –
The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.
On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.
Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.
Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).
All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.
In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
Key findings
Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).
Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.
SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.
The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).
The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.
Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.
Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
‘Eye-opening’ study
“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.
Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”
He added, “I think we need more long-term studies.”
The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT ACG 2023
IBD biologics, other therapies cleared of causing major adverse cardiovascular events
VANCOUVER –
In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.
Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.
“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.
“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.
The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
Therapies previously implicated in increased MACE risk
IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.
The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.
While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.
The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
Key findings
The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.
The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).
Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”
IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).
In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).
All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.
Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
Difference in IBD and rheumatoid arthritis populations
The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”
Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”
“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”
“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”
The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.
A version of this article first appeared on Medscape.com.
VANCOUVER –
In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.
Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.
“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.
“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.
The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
Therapies previously implicated in increased MACE risk
IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.
The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.
While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.
The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
Key findings
The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.
The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).
Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”
IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).
In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).
All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.
Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
Difference in IBD and rheumatoid arthritis populations
The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”
Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”
“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”
“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”
The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.
A version of this article first appeared on Medscape.com.
VANCOUVER –
In addition, biologics such as infliximab, adalimumab, golimumab, certolizumab, vedolizumab, natalizumab, and ustekinumab not only did not increase risk, but they were also linked to a significantly lower risk of major cardiovascular and thromboembolic events.
Risk reduction with biologics ranged from 15% for venous thromboembolism to 34% for myocardial infarction.
“The decrease in MACE with biologics was significant – and a bit surprising – but it correlates with the theory that by decreasing inflammation, there is a decrease in MACE,” said Miguel Regueiro, MD, chief of the Digestive Disease Institute at Cleveland Clinic, and senior author of the study.
“Our thought was that we would not see an increase in MACE and it would be equivalent between patients with IBD treated with advanced therapies and patients not treated with advanced therapies,” he told this news organization.
The findings “are consistent with some of the emerging long-term extension data from IBD clinical trials,” Dr. Regueiro reported at the ACG: American College of Gastroenterology annual scientific meeting. “And I’ll make an editorial comment for those that treat and practice in inflammatory bowel disease: I think these data continue to support, affirm, and hopefully comfort us.”
Therapies previously implicated in increased MACE risk
IBD itself is associated with increased MACE risk, likely because of chronic inflammation and endothelial dysfunction, the researchers note. While biologic and small molecule therapies are effective IBD treatments, some therapies have been implicated in an increased risk for MACE.
The Oral Surveillance postmarketing safety study of tofacitinib in rheumatoid arthritis, for example, linked the agent to higher MACE and venous thromboembolism rates vs. a TNF inhibitor. As a result, the FDA restricted the JAK inhibitor drug class that includes tofacitinib.
While long-term extension studies in IBD have not linked oral small molecules to increases in MACE, the sample sizes and duration of follow-up have been limited, the authors noted. For this reason, Dr. Regueiro and colleagues decided to further evaluate the potential associations in people with IBD.
The cohorts included 67,607 adults with IBD taking a biologic and another 67,607 with IBD not receiving a biologic between January 2021 and June 2023. The researchers also compared 3,194 adults with IBD taking an oral small molecule treatment vs. another 3,194 people with IBD not receiving these medications. These large sample sizes were possible through use of TriNetX, a large U.S. claims database that includes millions of patients.
Key findings
The propensity matched study revealed that adults with IBD on biologics had a significantly lower risk for coronary artery disease (adjusted odds ratio, 0.69; 95% confidence interval, 0.66-0.72; P < .0001), myocardial infarction (aOR, 0.66; 95% CI, 0.61-0.72; P < .0001) or stroke (aOR, 0.71; 95% CI, 0.65-0.77; P < .0001), compared with IBD patients not on biological therapy.
The researchers also found a lower risk for venous thromboembolism associated with biologics (aOR, 0.85; 95% CI, 0.81-0.89; P < .0001).
Dr. Regueiro said that active inflammation in the bowel or anywhere in the body is associated with higher rates of blood clot formation. “The thought is that decreasing inflammation with treatment may actually decrease the rates of blood clots. So, in essence, we think that biologics may actually decrease MACE.”
IBD patients receiving an oral small molecule did not have a significantly increased risk for coronary artery disease (aOR, 1.05; 95% CI, 0.82-1.33; P = .7148) or myocardial infarction (aOR, 1.04; 95% CI, 0.60-1.78; P = .8903). The risk of stroke was lower but not significantly different (aOR, 0.87; 95% CI, 0.57-1.33; P = .5148).
In addition, there was no significant change in risk for venous thromboembolism (aOR 1.07; 95% CI, 0.83-1.39; P = .5957).
All cohorts were matched for age, race, sex, cardiovascular risk factors, and medications including immunomodulators, 5-aminosalicylic acids, and steroids. MACE and VTE were noted by ICD-10 codes at least 30 days after starting treatment.
Strengths of the study included large sample size, diverse cohorts, and propensity score matching. Limitations included the study’s retrospective design.
Difference in IBD and rheumatoid arthritis populations
The authors noted: “Although further study is needed, it is possible that adequate treatment of bowel inflammation in IBD patients results in a decreased risk of MACE.”
Dr. Regueiro and colleagues are updating and expanding the research to increase the number of patients. They are also planning to evaluate the long-term extension data with individual biologics and small molecules to assess the consistency of their findings. “On preliminary glance, we believe that our results will be consistent with future study.”
“When you look at the studies, the increase in cardiac risk issues we’re seeing are in rheumatoid arthritis. And when we look at the patients with inflammatory bowel disease, we don’t see it,” session co-moderator John Leighton, MD, said when asked to comment. “So we think that there is a difference in the two populations, and this study gives further credence to that.”
“There are probably some high-risk populations that we still want to be careful with,” added Dr. Leighton, professor of medicine and chair of the division of gastroenterology at Mayo Clinic in Phoenix. “But the risk is not as great as they initially saw in the rheumatoid [arthritis] patients – and it’s a good thing because these drugs work very well.”
The study was independently supported. Lead author Dr. Qapaja had no relevant financial relationships. Dr. Regueiro is an advisory committee or board member and consultant for Alfasigma, Allergan, Amgen, Eli Lilly, Miraca Labs, Prometheus, Salix, Seres, and Target RWE. He serves in these roles and receives unrestricted educational grants from AbbVie, Bristol-Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer, Takeda, and UCB. He also receives royalties from Wolters Kluwer Health. Dr. Leighton is an advisory committee/board member for Braintree.
A version of this article first appeared on Medscape.com.
AT ACG 2023