Upper GI Tract

Gastroparesis can be tricky to diagnose and treat, in part because its symptoms can be difficult to distinguish from functional dyspepsia. A new clinical practice update from the American Gastroenterological Association aims to help physicians treat medically refractory gastroparesis with practical advice stemming from expert opinion and a literature review.

Although gastroparesis can be caused by known factors such as diabetes and medications, the largest group is idiopathic. The authors define medically refractory gastroparesis as symptoms that are not due to medication use, that continue despite dietary changes and first-line treatment with metoclopramide.

Heiko119/Thinkstock

Although the authors outline several best practice advice statements on symptom identification and management, they acknowledge that much uncertainty still exists. “Our knowledge gap remains vast, and areas for future research include study of pathophysiology and etiology, as well as identification of clinical and investigation-based predictors of response to each management approach,” the authors wrote. Their report is in Clinical Gastroenterology and Hepatology.

They also call for research to identify gastroparesis phenotypes that are most likely to respond to individual management approaches.

Common gastroparesis symptoms include nausea, vomiting, early satiety, bloating, postprandial fullness, abdominal pain, and weight loss. Many of these overlap with functional dyspepsia (FD). In fact, one study found that 42% of gastroparesis could be reclassified as having functional dyspepsia, and 37% of FD patients as having gastroparesis.

About 5 million adults in the United States, and 7.2% of the world population, report gastroparesis-like symptoms. The similarities between the two groups poses a significant diagnostic challenge. However, a careful history, physical exam, and appropriate diagnostic tests should allow the physician to rule out other conditions that may mimic gastroparesis. Repeating scintigraphy may change diagnosis from gastroparesis to FD or vice versa, but the authors note that this technique is often performed incorrectly and so should be conducted at centers that closely follow guidelines. They suggest a 4 hour meal-based test of gastric emptying over the wireless motility capsule because it provides a better physiological assessment.

They also suggest that treatment should focus on the most bothersome symptom, along with reducing the potential for complications such as esophagitis, malnutrition, and weight loss, as well as improving quality of life.

There are medications available for nausea and vomiting, although most have not been studied in large randomized controlled trials. These agents include domperidone, 5-hydroxytryptamine₃ receptor antagonists, neurokinin receptor antagonists, and phenothiazine antipsychotics.

There are also medications available to increase the rate of gastric emptying. Erythromycin can be used intravenously or orally ahead of meals, while the 5-HT4 receptor agonist velusetrag improved gastric emptying in healthy volunteers with no sign of cardiac side effects. The commonly available 5-HT4 agonist prucalopride has also shown promise in improving gastric emptying.

For visceral pain, the authors suggest not using opioids because they may slow gastric emptying and increase pain perception. It is believed that neuromodulators such as tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may reduce perception of pain, but there is limited high-quality evidence available for these therapies. The authors suggest that higher potency tertiary tricyclic amines such as amitriptyline or imipramine may be effective, particularly in diabetic gastroparesis since they provide relief in FD.

Nonpharmaceutical options include gastric electrical stimulation (GES), which improves refractory nausea and vomiting in some patients with gastroparesis, but does not accelerate gastric emptying. It may also improve glycemic control, nutritional status, and quality of life. The treatment may be well suited to opioid-free patients with refractory or intractable nausea and vomiting whose predominant symptom is not abdominal pain.

Other therapies focus on the pylorus and its role in gastric emptying, which can be impaired as a result of abnormalities of pyloric tone and pressure. Functional lumen imaging probe (FLIP) can be used to probe pyloric tone and pressure, but it is expensive, invasive, and not widely available.

Outside of clinical trial settings, the authors advise against the use of intrapyloric botulinum toxic injection and transpyloric stent placement. Per oral endoscopic myotomy (POEM) has shown some efficacy at improving symptoms and reducing gastric emptying times, but it has not been studied in sham-controlled trials. The authors call the technique intriguing, but say it should not be considered a first-line therapy, and should be performed only at tertiary centers with expert motility specialists and endoscopists.

In extreme cases, enteral nutrition may be necessary, and a transjejunal tube or combined gastrojejunostomy tube should be emplaced beyond the pylorus. In a retrospective case series, patients experienced weight recovery with acceptable morbidity and mortality, and the implant was removed at an average of 20 months.

The authors have consulted or been on scientific advisory boards for Salix, Ironwood, Allergan, Arena, Allakos, Medtronic, Diversatek, Takeda, Quintiles, and IsoThrive.

This article was updated Feb. 17, 2022.

Gastroparesis can be tricky to diagnose and treat, in part because its symptoms can be difficult to distinguish from functional dyspepsia. A new clinical practice update from the American Gastroenterological Association aims to help physicians treat medically refractory gastroparesis with practical advice stemming from expert opinion and a literature review.

Although gastroparesis can be caused by known factors such as diabetes and medications, the largest group is idiopathic. The authors define medically refractory gastroparesis as symptoms that are not due to medication use, that continue despite dietary changes and first-line treatment with metoclopramide.

Heiko119/Thinkstock

Although the authors outline several best practice advice statements on symptom identification and management, they acknowledge that much uncertainty still exists. “Our knowledge gap remains vast, and areas for future research include study of pathophysiology and etiology, as well as identification of clinical and investigation-based predictors of response to each management approach,” the authors wrote. Their report is in Clinical Gastroenterology and Hepatology.

They also call for research to identify gastroparesis phenotypes that are most likely to respond to individual management approaches.

Common gastroparesis symptoms include nausea, vomiting, early satiety, bloating, postprandial fullness, abdominal pain, and weight loss. Many of these overlap with functional dyspepsia (FD). In fact, one study found that 42% of gastroparesis could be reclassified as having functional dyspepsia, and 37% of FD patients as having gastroparesis.

About 5 million adults in the United States, and 7.2% of the world population, report gastroparesis-like symptoms. The similarities between the two groups poses a significant diagnostic challenge. However, a careful history, physical exam, and appropriate diagnostic tests should allow the physician to rule out other conditions that may mimic gastroparesis. Repeating scintigraphy may change diagnosis from gastroparesis to FD or vice versa, but the authors note that this technique is often performed incorrectly and so should be conducted at centers that closely follow guidelines. They suggest a 4 hour meal-based test of gastric emptying over the wireless motility capsule because it provides a better physiological assessment.

They also suggest that treatment should focus on the most bothersome symptom, along with reducing the potential for complications such as esophagitis, malnutrition, and weight loss, as well as improving quality of life.

There are medications available for nausea and vomiting, although most have not been studied in large randomized controlled trials. These agents include domperidone, 5-hydroxytryptamine₃ receptor antagonists, neurokinin receptor antagonists, and phenothiazine antipsychotics.

There are also medications available to increase the rate of gastric emptying. Erythromycin can be used intravenously or orally ahead of meals, while the 5-HT4 receptor agonist velusetrag improved gastric emptying in healthy volunteers with no sign of cardiac side effects. The commonly available 5-HT4 agonist prucalopride has also shown promise in improving gastric emptying.

For visceral pain, the authors suggest not using opioids because they may slow gastric emptying and increase pain perception. It is believed that neuromodulators such as tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may reduce perception of pain, but there is limited high-quality evidence available for these therapies. The authors suggest that higher potency tertiary tricyclic amines such as amitriptyline or imipramine may be effective, particularly in diabetic gastroparesis since they provide relief in FD.

Nonpharmaceutical options include gastric electrical stimulation (GES), which improves refractory nausea and vomiting in some patients with gastroparesis, but does not accelerate gastric emptying. It may also improve glycemic control, nutritional status, and quality of life. The treatment may be well suited to opioid-free patients with refractory or intractable nausea and vomiting whose predominant symptom is not abdominal pain.

Other therapies focus on the pylorus and its role in gastric emptying, which can be impaired as a result of abnormalities of pyloric tone and pressure. Functional lumen imaging probe (FLIP) can be used to probe pyloric tone and pressure, but it is expensive, invasive, and not widely available.

Outside of clinical trial settings, the authors advise against the use of intrapyloric botulinum toxic injection and transpyloric stent placement. Per oral endoscopic myotomy (POEM) has shown some efficacy at improving symptoms and reducing gastric emptying times, but it has not been studied in sham-controlled trials. The authors call the technique intriguing, but say it should not be considered a first-line therapy, and should be performed only at tertiary centers with expert motility specialists and endoscopists.

In extreme cases, enteral nutrition may be necessary, and a transjejunal tube or combined gastrojejunostomy tube should be emplaced beyond the pylorus. In a retrospective case series, patients experienced weight recovery with acceptable morbidity and mortality, and the implant was removed at an average of 20 months.

The authors have consulted or been on scientific advisory boards for Salix, Ironwood, Allergan, Arena, Allakos, Medtronic, Diversatek, Takeda, Quintiles, and IsoThrive.

This article was updated Feb. 17, 2022.

Gastroparesis can be tricky to diagnose and treat, in part because its symptoms can be difficult to distinguish from functional dyspepsia. A new clinical practice update from the American Gastroenterological Association aims to help physicians treat medically refractory gastroparesis with practical advice stemming from expert opinion and a literature review.

Although gastroparesis can be caused by known factors such as diabetes and medications, the largest group is idiopathic. The authors define medically refractory gastroparesis as symptoms that are not due to medication use, that continue despite dietary changes and first-line treatment with metoclopramide.

Heiko119/Thinkstock

Although the authors outline several best practice advice statements on symptom identification and management, they acknowledge that much uncertainty still exists. “Our knowledge gap remains vast, and areas for future research include study of pathophysiology and etiology, as well as identification of clinical and investigation-based predictors of response to each management approach,” the authors wrote. Their report is in Clinical Gastroenterology and Hepatology.

They also call for research to identify gastroparesis phenotypes that are most likely to respond to individual management approaches.

Common gastroparesis symptoms include nausea, vomiting, early satiety, bloating, postprandial fullness, abdominal pain, and weight loss. Many of these overlap with functional dyspepsia (FD). In fact, one study found that 42% of gastroparesis could be reclassified as having functional dyspepsia, and 37% of FD patients as having gastroparesis.

About 5 million adults in the United States, and 7.2% of the world population, report gastroparesis-like symptoms. The similarities between the two groups poses a significant diagnostic challenge. However, a careful history, physical exam, and appropriate diagnostic tests should allow the physician to rule out other conditions that may mimic gastroparesis. Repeating scintigraphy may change diagnosis from gastroparesis to FD or vice versa, but the authors note that this technique is often performed incorrectly and so should be conducted at centers that closely follow guidelines. They suggest a 4 hour meal-based test of gastric emptying over the wireless motility capsule because it provides a better physiological assessment.

They also suggest that treatment should focus on the most bothersome symptom, along with reducing the potential for complications such as esophagitis, malnutrition, and weight loss, as well as improving quality of life.

There are medications available for nausea and vomiting, although most have not been studied in large randomized controlled trials. These agents include domperidone, 5-hydroxytryptamine₃ receptor antagonists, neurokinin receptor antagonists, and phenothiazine antipsychotics.

There are also medications available to increase the rate of gastric emptying. Erythromycin can be used intravenously or orally ahead of meals, while the 5-HT4 receptor agonist velusetrag improved gastric emptying in healthy volunteers with no sign of cardiac side effects. The commonly available 5-HT4 agonist prucalopride has also shown promise in improving gastric emptying.

For visceral pain, the authors suggest not using opioids because they may slow gastric emptying and increase pain perception. It is believed that neuromodulators such as tricyclic antidepressants (TCAs) and serotonin norepinephrine reuptake inhibitors (SNRIs) may reduce perception of pain, but there is limited high-quality evidence available for these therapies. The authors suggest that higher potency tertiary tricyclic amines such as amitriptyline or imipramine may be effective, particularly in diabetic gastroparesis since they provide relief in FD.

Nonpharmaceutical options include gastric electrical stimulation (GES), which improves refractory nausea and vomiting in some patients with gastroparesis, but does not accelerate gastric emptying. It may also improve glycemic control, nutritional status, and quality of life. The treatment may be well suited to opioid-free patients with refractory or intractable nausea and vomiting whose predominant symptom is not abdominal pain.

Other therapies focus on the pylorus and its role in gastric emptying, which can be impaired as a result of abnormalities of pyloric tone and pressure. Functional lumen imaging probe (FLIP) can be used to probe pyloric tone and pressure, but it is expensive, invasive, and not widely available.

Outside of clinical trial settings, the authors advise against the use of intrapyloric botulinum toxic injection and transpyloric stent placement. Per oral endoscopic myotomy (POEM) has shown some efficacy at improving symptoms and reducing gastric emptying times, but it has not been studied in sham-controlled trials. The authors call the technique intriguing, but say it should not be considered a first-line therapy, and should be performed only at tertiary centers with expert motility specialists and endoscopists.

In extreme cases, enteral nutrition may be necessary, and a transjejunal tube or combined gastrojejunostomy tube should be emplaced beyond the pylorus. In a retrospective case series, patients experienced weight recovery with acceptable morbidity and mortality, and the implant was removed at an average of 20 months.

The authors have consulted or been on scientific advisory boards for Salix, Ironwood, Allergan, Arena, Allakos, Medtronic, Diversatek, Takeda, Quintiles, and IsoThrive.

This article was updated Feb. 17, 2022.

Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

Among individuals with gastroesophageal reflux disease (GERD), a negative upper endoscopy is associated with decreased risk in incidence and mortality from gastrointestinal cancer. The benefit persisted through 5-10 years following the procedure.

The finding is similar to the survival benefit seen with colonoscopies and colorectal cancer, and may be attributable to endoscopic treatment of premalignant lesions.

“The relatively high incidence rate of upper gastrointestinal cancer in patients with GERD indicates that a one-time upper endoscopy may be beneficial,” wrote the authors, who were led by Dag Holmberg, MD, PhD, of the department of molecular medicine and surgery at the Karolinska Institutet and Karolinska University Hospital, both in Stockholm. The study was published in Gastroenterology.

GERD is the most frequent reason patients undergo an upper endoscopy, but the results are often negative. It is generally a benign condition, but can lead to Barrett’s esophagus, as well as esophageal and gastric cardia adenocarcinoma. Upper endoscopy can identify other esophageal cancers like gastric noncardia cancer and duodenal cancer, which may cause dyspepsia or GERD-like symptoms.

To determine the potential benefit of upper endoscopy, the researchers conducted a population-based, four-nation cohort study that included 1,062,740 individuals with GERD in Denmark, Finland, Norway, and Sweden. The data were gathered from national patient registries, cancer registries, and cause of death registries. The study encompassed data from 1979 through the end of 2018.

The median age was 58 years, and 52% of participants were women.

The researchers defined a negative endoscopy as no diagnosis of gastrointestinal cancer within 6 months of the procedure; 69.3% of procedures were negative.

During the follow-up period, 0.34% of participants developed and 0.27% died of upper gastrointestinal cancer. Among those with negative endoscopies, 0.23% developed and 0.22% died from upper gastrointestinal cancer.

Participants with a negative endoscopy had a lower risk of being diagnosed with upper gastrointestinal cancer during the follow-up period (adjusted hazard ratio, 0.45; 95% confidence interval, 0.43-0.48). The reduction in risk was similar across age sexes and age groups, but among procedures performed after 2008, the risk reduction was even higher (aHR, 0.34; P < .001).

The effect was strongest in the first year after the procedure, but it persisted out to 5 years before returning to baseline risk levels.

A negative endoscopy was also associated with decreased mortality risk from upper gastrointestinal cancer versus those who hadn’t had an endoscopy (aHR, 0.39; 95% CI, 0.37-0.42). The protective value continued for at least 10 years.

Esophageal adenocarcinoma developed in 0.12% of participants, and 0.10% died of the disease. Among those with a negative endoscopy, 0.09% developed adenocarcinoma, and 0.07% died (aHR vs. no upper endoscopy, 0.33; 95% CI, 0.30-0.37).

The rapid return to baseline risk was notable, and different from what occurs after negative colonoscopies. However, new tumors can readily form within one year, and the risk may reflect early malignant or premalignant lesions that were missed during the procedure.

In fact, a meta-analysis found that 11.3% of upper gastrointestinal cancers had escaped detection during an endoscopy in the previous 3 years before diagnosis, and case reviews of patients diagnosed with gastrointestinal cancer soon after an upper endoscopy usually reveal suspicious or indeterminate results that the endoscopist or pathologist missed.

Quality indicators for upper endoscopy include procedure time, rate of targeted biopsies, and computer-aided detection, but it isn’t clear what impact these measures have on outcomes. However, the greater risk reduction found with endoscopies performed more recently suggests that newer quality indicators and technological improvements may be improving outcomes.

The relatively low incidence of esophageal and gastric cancer in Western countries has discouraged widespread adoption of endoscopic screening, but the researchers point out that the risk of gastrointestinal cancer among individuals with GERD is similar to the risk of colorectal cancer in the 60-69 age group in the United States, for whom colonoscopy is recommended.

“The present study indicates that upper endoscopy may be beneficial for patients with GERD, but to make upper endoscopy screening more cost beneficial at its initiation, the target group may be limited to include patients at highest risk of cancer. Such previous cost-effectiveness studies have indicated that endoscopy is cost effective in men at aged 50 years or older with chronic GERD,” the authors wrote.

The study was funded by Swedish Research Council and Swedish Cancer Society. The authors disclosed no relevant conflicts of interest.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

TC-325, a bentonite-derived hemostatic powder, was not inferior to standard therapy for the endoscopic management of acute nonvariceal upper GI bleeding, according to a new study.

The findings from the study, lead investigator and study author James Y.W. Lau, MD, of the Prince of Wales Hospital in Hong Kong, said in an interview, suggest TC-325 could “be considered one of the primary endoscopic treatments to actively stop nonvariceal bleeding,” particularly in cases when other therapies prove unsuccessful. The study findings were published in Annals of Internal Medicine.

The study team noted that, after they first reported the use of TC-325 in active bleeding from gastroduodenal ulcers in 2011, there have been other studies of its use with acute nonvariceal upper GI bleeding, but to date there has been only two randomized controlled trials of it as a sole endoscopic treatment option for acute nonvariceal upper GI bleeding. To close this research gap, Dr. Lau and researchers enrolled 224 adult patients with acute bleeding from a nonvariceal source on upper GI endoscopy and randomly assigned these patients to receive either TC-325 (n = 111) or standard hemostatic treatment (n = 113). Standard endoscopic bleeding management consisted of contact thermocoagulation using a heater probe or bipolar probe, or hemoclipping with or without previously injected diluted epinephrine.

Success of assigned treatment was defined by the cessation of active bleeding as well as flattening of the protuberance or vessel with a heater or bipolar probe. For the primary outcome of the study, the investigators assessed the rate of bleeding control within 30 days following randomization. Additionally, the researchers compared the treatment groups to identify differences in the failure to control bleeding during the initial endoscopy and recurrent bleeding following hemostasis.

Treatment groups were even in regard to the proportions of patients with bleeding gastroduodenal ulcers (61.3% vs. 60.2%). A smaller proportion of patients in the TC-325 arm had a history of alcohol use (3.0% vs. 9.8%) and current use of NSAIDs (8.1% vs. 20.4%). The group assigned to TC-325 had more bleeding tumors (20.7% vs. 8.8%) and fewer Dieulafoy lesions (5.4% vs. 14.2%), compared with the standard treatment arm. Additionally, patients in the TC-325 group had a higher median Glasgow-Blatchford Score at hospital admission than the standard endoscopy management group (12 vs. 11, respectively; P < .05).

Although a greater proportion of patients assigned TC-325 had bleeding controlled within 30 days of randomization (90.1% vs. 81.4%; risk difference, 8.7 percentage points; 1-sided 95% CI, 0.95 percentage points), the researchers noted that the lower limit of the confidence interval for treatment difference “did not extend beyond the prespecified noninferiority margin of 10 percentage points, indicating that TC-325 is not inferior to standard treatment in the control of bleeding.”

Fewer failures of hemostasis were observed with TC-325 during index endoscopy (2.7% vs. 9.7%; odds ratio, 0.26; 95% CI, 0.07-0.95). After initial endoscopic control, recurrent bleeding was observed in 9 patients in the TC-325 arm and 10 patients in the standard treatment group.

The authors suggested that the low recurrent bleeding rate in the TC-325 arm may reflect enhanced responsiveness in the predominantly Asian study population, a group with lower parietal cell masses and higher rates of Helicobacter pylori infections. In an accompanying editorial published online in Annals of Internal Medicine, Alan N. Barkun, MD, McGill University and McGill University Health Centre in Montreal, and Ali Alali, MB BCh BAO, in the department of medicine at Kuwait University, Kuwait City, noted that “possible additional reasons for the enhanced effectiveness of TC-325 observed in the current trial may be its varied performance in the patients with nonulcer bleeding.”

No difference was found between the treatment strategies in terms of the need for additional interventions within 30 days. The need for further endoscopic treatment was reported in 7.2% of patients in the TC-325 groups versus 8.8% of patients assigned to standard treatment. In addition, further angiography was required in 1.8% and 3.5% of patients, while further surgery was required in 0.9% of patients treated with TC-325 versus none in the standard treatment group. Each group reported 14 deaths.

Dr. Lau noted that the study enrolled Asian patients who were more responsive to proton pump inhibitor therapy, which may limit the generalizability of the findings. “We also included patients with mixed etiologies,” he added. “Studies that focus on specific lesions would further inform our practice, and larger observational studies are required to understand failures with TC-325.”

Based on the study findings, corresponding editorial author Dr. Barkun wrote that “TC-325 can be used alone in nonvariceal upper gastrointestinal bleeding or as rescue therapy but should be reserved for patients with actively bleeding lesions” and suggests the treatment option “is likely one of the most effective modalities in achieving immediate hemostasis.”

The researchers reported no conflicts of interest with the pharmaceutical industry. The editorialists also reported no disclosures of interest.

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

LAS VEGAS – In the treatment of Helicobacter pylori infection, combination therapies using the oral potassium-competitive acid blocker vonoprazan were superior to standard proton pump inhibitor (PPI)–based triple therapy, producing higher eradication rates, according to combined data from a U.S. and a European phase 3 randomized, controlled trial.

Vonoprazan has been submitted to the Food and Drug Administration for approval with a Fast Track designation in combination with amoxicillin and clarithromycin (triple therapy) or amoxicillin alone (dual therapy) for treating H. pylori infection. It has already been approved in Japan for the treatment of gastric and duodenal ulcers, reflux esophagitis, secondary prevention of low-dose aspirin– or nonsteroidal anti-inflammatory drug–induced gastric mucosal damage, and for first and second-line H. pylori eradication therapy.

Study details

The study included 1,046 treatment-naive patients who had dyspepsia, a recent or new diagnosis of a nonbleeding peptic ulcer, a history of a peptic ulcer, or long-term stable use of an NSAID. Patients were randomized to PPI-based triple therapy (lansoprazole, amoxicillin, clarithromycin), vonoprazan triple therapy (plus amoxicillin, clarithromycin), or vonoprazan dual therapy (amoxicillin). The treatment period was 14 days, followed by 13C urea breath test (UBT) 4 weeks after treatment.

The researchers conducted several analyses, including: Modified intention-to-treat analyses, which included all enrollees; per protocol analyses, which included patients who took at least 75% of each study medication and underwent 13C UBT in the expected time frame; and a safety population of all patients who took at least one study drug.

Among patients with H. pylori strains that were not resistant to clarithromycin, the PPI-based triple-therapy group had an eradication rate of 78.8%, compared with 84.7% in the vonoprazan triple-therapy group (P < .0001), and 78.5% in the vonoprazan dual-therapy group (P = .0037). In the per protocol analysis, PPI-based triple therapy eradicated H. pylori 82.1% of the time, compared with 90.4% in the vonoprazan triple-therapy group (P < .0001) and 81.2% in the vonoprazan dual-therapy group (P = .0077). Both vonoprazan treatment groups were noninferior to PPI-based triple therapy.

A prespecified exploratory analysis found that vonoprazan triple therapy outperformed PPI-based triple therapy in the modified intention-to-treat population (P = .0408) and the per protocol population (P = .0059).

Among patients with clarithromycin-resistant strains of H. pylori, in the modified intention-to-treat population, 31.9% achieved eradication with PPI triple therapy, compared with 65.8% in the vonoprazan triple-therapy group, and 69.6% in the vonoprazan dual-therapy group. In the per protocol population, the numbers were 29.0% versus 67.2% and 79.5%, respectively (P < .0001 for both versus PPI triple therapy).

Among all patients, in the modified intention-to-treat population, 68.5% achieved eradication with PPI triple therapy, 80.8% with vonoprazan triple therapy (P =. 0001), and 77.2% with vonoprazan dual therapy (P = .0063)*. In the per protocol population, the numbers were 70.0%, 85.7% (P < .0001), and 81.1% (P = .0013), respectively.

Safety outcomes were similar among the three groups, with treatment-emergent adverse events occurring in 34.5% of the PPI triple-therapy group (1.2% discontinued), 34.1% of the vonoprazan triple-therapy group (2.3% discontinued), and 29.9% in the vonoprazan dual-therapy group (0.9% discontinued).

Fighting against resistance

The efficacy of PPI-based clarithromycin-based triple therapy has fallen below 80% in the United States and Europe over the past few decades, largely because of antibiotic resistance, said William Chey, MD, during a presentation of the results at the annual meeting of the American College of Gastroenterology. Dr. Chey is a professor of medicine and director of the GI physiology laboratory at Michigan Medicine.

Vonoprazan is more stable in acid than are PPIs, and produces greater and more durable acid reduction, according to Dr. Chey. That’s important for two reasons: One is that some antibiotics are acid-labile, and so may have their efficacy directly impacted in a more acidic environment. The other factor is that most antibiotics work better on bacteria that are actively replicating, and H. pylori reproduces better in a more neutral environment. “So, you increase the replication, you increase the bioavailability of the antibiotics. And therefore, hopefully, that underlies why we see it working better in the patients with [antibiotic] resistance,” Dr. Chey said in an interview.

It remains to be seen whether or not the drug will receive FDA approval, but he pointed to other regimens like bismuth quadruple therapy and rifabutin-based triple therapy that are already available. “If I had the choice, I would never use a PPI-based triple therapy again. People should not be doing that,” said Dr. Chey.

“More successful H. pylori eradication regimens are certainly needed, and these results are particularly relevant and interesting given the increasing failure of initial treatment regimens,” said Kimberly Harer, MD, who moderated the session. She noted that the secondary analysis of patients with clarithromycin-resistant infections was particularly relevant. “The superiority analysis indicating vonoprazan triple therapy resulted in increased H. pylori eradication compared to lanzoprazole triple therapy was especially interesting,” said Dr. Harer, who is a clinical lecturer at University of Michigan Health, Ann Arbor.

One downside to the study is that it didn’t compare vonoprazan combinations to quadruple therapy of a PPI, bismuth, tetracycline, and a nitroimidazole, said Joseph Jennings, MD, who was asked to comment on the study. Other treatment approaches include sequential antibiotics and other combinations. Dr. Jennings also highlighted the findings that the vonoprazan regimens were superior against clarithromycin-resistant strains. “The more different regimens we can add to the armamentarium, the better chance we have because the resistant patterns fluctuate all throughout the world,” said Dr. Jennings, who is an assistant professor of medicine at Georgetown University and director of the center for GI bleeding at MedStar Georgetown University Hospital, both in Washington.

He also pointed out that physicians can face a conundrum when patients fail multiple lines of therapy and have testing done that shows high levels of resistance. Some have allergies that prevent them from turning to other antibiotics. “That’s a market where lots of doctors struggle. Something like this would be a nice add-on,” said Dr. Jennings.

The study was funded by Phathom Pharmaceuticals.** Dr. Chey has consulted and/or received research support from Abbvie, Alfasigma, Allakos, Alnylam, Bayer, Bioamerica, Cosmo, Intrinsic Medicine, Ironwood, Modify Health, My GI Health, My Nutrition Health, Nestle, Phathom Pharmaceuticals, QOL Medical, Redhill, Salix/Valeant, Takeda, Urovant, and Vibrant. Dr. Harer and Dr. Jennings have no relevant financial disclosures.

*Correction, 10/29/21: An earlier version of this article misstated the percentage of patients in the modified intention-to-treat population who achieved eradication with vonoprazan triple therapy.

**Correction, 10/29/21: An earlier version of this article misstated the name of Phathom Pharmaceuticals.

LAS VEGAS – Functional lumen imaging probe (FLIP) was equivalent to high-resolution manometry (HRM) in predicting clinical response by Eckardt score 6 months or more after per oral endoscopic myotomy (POEM) for achalasia or esophagogastric junction (EGJ) outlet obstruction (EGJOO).

Measures for clinical response following lower esophageal sphincter myotomy procedures include Eckardt Score, timed barium esophagram, HRM, and FLIP. However, since FLIP is a relatively new technique, there are few clinical data comparing its efficacy versus HRM in patients who have a positive response to POEM measured by the Eckardt score, according to John DeWitt, MD, who presented the research at the annual meeting of the American College of Gastroenterology.

FLIP can be performed during a follow-up endoscopy while a patient is sedated, while HRM requires the patient to be awake. Some patients find the procedure intolerable, and Dr. DeWitt estimates that 10%-20% of patients don’t return for follow-up assessments because of the discomfort.

“[FLIP] is a relatively new technology, the role of which is still being discovered. We have a lot more information on the diagnosis side of things. The role in follow-up, particularly after myotomy, is really not defined well. This is the first study to my knowledge that has evaluated manometry and FLIP head-to-head to compare patient-reported outcomes,” said Dr. DeWitt in an interview. He is a professor of medicine and the director of endoscopic ultrasound at Indiana University Medical Center, in Indianapolis.
 

Going head-to-head

The researchers conducted a retrospective, single-center study of 265 consecutive patients who underwent POEM for achalasia or EGJOO from 2016 through 2020. A clinical response was defined as an Eckardt score ≤3, EGJ distensibility index (EGJ-DI) higher than 2.8 mm²/mm Hg, maximum integrated relaxation pressure (IRP) <15 mm Hg, or a maximum EGJ diameter greater than 14 mm at any balloon distension.

In all, 126 patients returned for follow-up and completed an upper endoscopy with FLIP, HRM, and Eckardt scores within a 6-12 month period after the POEM procedure.

With respect to HRM, an IRP measurement <15 mm Hg predicted post-POEM Eckardt score with a sensitivity of 86.7% (95% confidence interval, 79.3-92.2) and a specificity of 33.3% (95% CI, 4.3-77.7), with an area under the curve of 0.60 (95% CI, 0.39-0.81). A maximum EJG diameter ≥ 14 mm had a sensitivity of 77.5% (95% CI, 69.0-84.6) and a specificity of 33.3% (95% CI, 4.3-77.7), with an AUC of 0.55 (95% CI, 0.34-0.76).

The performance was similar with FLIP: EGJ-DI > 2.8 mm²/mm Hg at any balloon setting had a sensitivity of 95.0% (95% CI, 89.4-98.1) and a specificity% of 0.0, and an AUC of 0.53 (95% CI, 0.51-0.55). A similar measurement at 40 mL or 50 mL distension had a sensitivity of 93.3% (95% CI, 87.3-97.1) and a specificity of 16.7% (95% CI, 0.4-64.1), with an AUC of 0.55 (95% CI, 0.39-0.72). Receiver operator characteristic analysis showed no significant difference between ability of FLIP and HRM to predict a normal Eckardt score.

If the study is repeated in other patient populations, Dr. DeWitt hopes that it could eliminate manometry altogether in a large majority of patients. “That would be potentially a game changer for bringing patients back to see how well they’re doing,” said Dr. DeWitt.

Not all patients who undergo POEM would be good candidates for FLIP, said Dr. DeWitt. The study was limited to patients with hypertension in the lower esophageal sphincter. Other disorders such as diffuse esophageal spasm, jackhammer esophagus, and type III achalasia would not likely be candidates for FLIP. “Those patients are going to probably still need manometry because if the esophageal body abnormalities are still present, then repeat testing might need to be performed,” said Dr. DeWitt. Still, he estimated about 80% of patients could be eligible for FLIP instead.
 

Impact on patients

“I think it’s interesting new data,” said Patrick Young, MD, who comoderated the session where the research was presented. He noted that the treatment of achalasia is evolving away from surgery, and the techniques to measure response are evolving along with it. “As we progress in that technology and using that procedure, we need to understand better how to follow those people up. I think adding this new device may help us to understand who’s going to respond well, and who’s not going to respond well. This is an early investigation, so I think we’ll need to do trials, but I think this is a good first step,” said Dr. Young, who is a professor of medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Comoderator Mohammad Yaghoobi, MD, also praised the study, but noted that the cost of FLIP could be a concern. “We want to have a reasonable ratio of the cost versus the effectiveness,” said Dr. Yaghoobi, who is an associate professor of medicine at McMaster University in Hamilton, Ont.

Dr. DeWitt, Dr. Young, and Dr. Yaghoobi had no relevant disclosures.

LAS VEGAS – Functional lumen imaging probe (FLIP) was equivalent to high-resolution manometry (HRM) in predicting clinical response by Eckardt score 6 months or more after per oral endoscopic myotomy (POEM) for achalasia or esophagogastric junction (EGJ) outlet obstruction (EGJOO).

Measures for clinical response following lower esophageal sphincter myotomy procedures include Eckardt Score, timed barium esophagram, HRM, and FLIP. However, since FLIP is a relatively new technique, there are few clinical data comparing its efficacy versus HRM in patients who have a positive response to POEM measured by the Eckardt score, according to John DeWitt, MD, who presented the research at the annual meeting of the American College of Gastroenterology.

FLIP can be performed during a follow-up endoscopy while a patient is sedated, while HRM requires the patient to be awake. Some patients find the procedure intolerable, and Dr. DeWitt estimates that 10%-20% of patients don’t return for follow-up assessments because of the discomfort.

“[FLIP] is a relatively new technology, the role of which is still being discovered. We have a lot more information on the diagnosis side of things. The role in follow-up, particularly after myotomy, is really not defined well. This is the first study to my knowledge that has evaluated manometry and FLIP head-to-head to compare patient-reported outcomes,” said Dr. DeWitt in an interview. He is a professor of medicine and the director of endoscopic ultrasound at Indiana University Medical Center, in Indianapolis.
 

Going head-to-head

The researchers conducted a retrospective, single-center study of 265 consecutive patients who underwent POEM for achalasia or EGJOO from 2016 through 2020. A clinical response was defined as an Eckardt score ≤3, EGJ distensibility index (EGJ-DI) higher than 2.8 mm²/mm Hg, maximum integrated relaxation pressure (IRP) <15 mm Hg, or a maximum EGJ diameter greater than 14 mm at any balloon distension.

In all, 126 patients returned for follow-up and completed an upper endoscopy with FLIP, HRM, and Eckardt scores within a 6-12 month period after the POEM procedure.

With respect to HRM, an IRP measurement <15 mm Hg predicted post-POEM Eckardt score with a sensitivity of 86.7% (95% confidence interval, 79.3-92.2) and a specificity of 33.3% (95% CI, 4.3-77.7), with an area under the curve of 0.60 (95% CI, 0.39-0.81). A maximum EJG diameter ≥ 14 mm had a sensitivity of 77.5% (95% CI, 69.0-84.6) and a specificity of 33.3% (95% CI, 4.3-77.7), with an AUC of 0.55 (95% CI, 0.34-0.76).

The performance was similar with FLIP: EGJ-DI > 2.8 mm²/mm Hg at any balloon setting had a sensitivity of 95.0% (95% CI, 89.4-98.1) and a specificity% of 0.0, and an AUC of 0.53 (95% CI, 0.51-0.55). A similar measurement at 40 mL or 50 mL distension had a sensitivity of 93.3% (95% CI, 87.3-97.1) and a specificity of 16.7% (95% CI, 0.4-64.1), with an AUC of 0.55 (95% CI, 0.39-0.72). Receiver operator characteristic analysis showed no significant difference between ability of FLIP and HRM to predict a normal Eckardt score.

If the study is repeated in other patient populations, Dr. DeWitt hopes that it could eliminate manometry altogether in a large majority of patients. “That would be potentially a game changer for bringing patients back to see how well they’re doing,” said Dr. DeWitt.

Not all patients who undergo POEM would be good candidates for FLIP, said Dr. DeWitt. The study was limited to patients with hypertension in the lower esophageal sphincter. Other disorders such as diffuse esophageal spasm, jackhammer esophagus, and type III achalasia would not likely be candidates for FLIP. “Those patients are going to probably still need manometry because if the esophageal body abnormalities are still present, then repeat testing might need to be performed,” said Dr. DeWitt. Still, he estimated about 80% of patients could be eligible for FLIP instead.
 

Impact on patients

“I think it’s interesting new data,” said Patrick Young, MD, who comoderated the session where the research was presented. He noted that the treatment of achalasia is evolving away from surgery, and the techniques to measure response are evolving along with it. “As we progress in that technology and using that procedure, we need to understand better how to follow those people up. I think adding this new device may help us to understand who’s going to respond well, and who’s not going to respond well. This is an early investigation, so I think we’ll need to do trials, but I think this is a good first step,” said Dr. Young, who is a professor of medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Comoderator Mohammad Yaghoobi, MD, also praised the study, but noted that the cost of FLIP could be a concern. “We want to have a reasonable ratio of the cost versus the effectiveness,” said Dr. Yaghoobi, who is an associate professor of medicine at McMaster University in Hamilton, Ont.

Dr. DeWitt, Dr. Young, and Dr. Yaghoobi had no relevant disclosures.

LAS VEGAS – Functional lumen imaging probe (FLIP) was equivalent to high-resolution manometry (HRM) in predicting clinical response by Eckardt score 6 months or more after per oral endoscopic myotomy (POEM) for achalasia or esophagogastric junction (EGJ) outlet obstruction (EGJOO).

Measures for clinical response following lower esophageal sphincter myotomy procedures include Eckardt Score, timed barium esophagram, HRM, and FLIP. However, since FLIP is a relatively new technique, there are few clinical data comparing its efficacy versus HRM in patients who have a positive response to POEM measured by the Eckardt score, according to John DeWitt, MD, who presented the research at the annual meeting of the American College of Gastroenterology.

FLIP can be performed during a follow-up endoscopy while a patient is sedated, while HRM requires the patient to be awake. Some patients find the procedure intolerable, and Dr. DeWitt estimates that 10%-20% of patients don’t return for follow-up assessments because of the discomfort.

“[FLIP] is a relatively new technology, the role of which is still being discovered. We have a lot more information on the diagnosis side of things. The role in follow-up, particularly after myotomy, is really not defined well. This is the first study to my knowledge that has evaluated manometry and FLIP head-to-head to compare patient-reported outcomes,” said Dr. DeWitt in an interview. He is a professor of medicine and the director of endoscopic ultrasound at Indiana University Medical Center, in Indianapolis.
 

Going head-to-head

The researchers conducted a retrospective, single-center study of 265 consecutive patients who underwent POEM for achalasia or EGJOO from 2016 through 2020. A clinical response was defined as an Eckardt score ≤3, EGJ distensibility index (EGJ-DI) higher than 2.8 mm²/mm Hg, maximum integrated relaxation pressure (IRP) <15 mm Hg, or a maximum EGJ diameter greater than 14 mm at any balloon distension.

In all, 126 patients returned for follow-up and completed an upper endoscopy with FLIP, HRM, and Eckardt scores within a 6-12 month period after the POEM procedure.

With respect to HRM, an IRP measurement <15 mm Hg predicted post-POEM Eckardt score with a sensitivity of 86.7% (95% confidence interval, 79.3-92.2) and a specificity of 33.3% (95% CI, 4.3-77.7), with an area under the curve of 0.60 (95% CI, 0.39-0.81). A maximum EJG diameter ≥ 14 mm had a sensitivity of 77.5% (95% CI, 69.0-84.6) and a specificity of 33.3% (95% CI, 4.3-77.7), with an AUC of 0.55 (95% CI, 0.34-0.76).

The performance was similar with FLIP: EGJ-DI > 2.8 mm²/mm Hg at any balloon setting had a sensitivity of 95.0% (95% CI, 89.4-98.1) and a specificity% of 0.0, and an AUC of 0.53 (95% CI, 0.51-0.55). A similar measurement at 40 mL or 50 mL distension had a sensitivity of 93.3% (95% CI, 87.3-97.1) and a specificity of 16.7% (95% CI, 0.4-64.1), with an AUC of 0.55 (95% CI, 0.39-0.72). Receiver operator characteristic analysis showed no significant difference between ability of FLIP and HRM to predict a normal Eckardt score.

If the study is repeated in other patient populations, Dr. DeWitt hopes that it could eliminate manometry altogether in a large majority of patients. “That would be potentially a game changer for bringing patients back to see how well they’re doing,” said Dr. DeWitt.

Not all patients who undergo POEM would be good candidates for FLIP, said Dr. DeWitt. The study was limited to patients with hypertension in the lower esophageal sphincter. Other disorders such as diffuse esophageal spasm, jackhammer esophagus, and type III achalasia would not likely be candidates for FLIP. “Those patients are going to probably still need manometry because if the esophageal body abnormalities are still present, then repeat testing might need to be performed,” said Dr. DeWitt. Still, he estimated about 80% of patients could be eligible for FLIP instead.
 

Impact on patients

“I think it’s interesting new data,” said Patrick Young, MD, who comoderated the session where the research was presented. He noted that the treatment of achalasia is evolving away from surgery, and the techniques to measure response are evolving along with it. “As we progress in that technology and using that procedure, we need to understand better how to follow those people up. I think adding this new device may help us to understand who’s going to respond well, and who’s not going to respond well. This is an early investigation, so I think we’ll need to do trials, but I think this is a good first step,” said Dr. Young, who is a professor of medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md.

Comoderator Mohammad Yaghoobi, MD, also praised the study, but noted that the cost of FLIP could be a concern. “We want to have a reasonable ratio of the cost versus the effectiveness,” said Dr. Yaghoobi, who is an associate professor of medicine at McMaster University in Hamilton, Ont.

Dr. DeWitt, Dr. Young, and Dr. Yaghoobi had no relevant disclosures.

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

LAS VEGAS –Data from the 28-week extension of the Liberty EoE TREET phase 3 clinical trial showed that the anti–interleukin-4/IL-13 antibody dupilumab led to long-term improvement in eosinophil count, histology, and patient-reported symptoms of eosinophilic esophagitis (EoE) out to 28 weeks. Dupilumab is Food and Drug Administration approved for the treatment of atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis.

Many patients don’t respond to the standard therapies of proton pump inhibitors, steroids, or diet. Some evidence suggests that EoE might be driven by type 2 inflammation, and dupilumab’s effect on the shared receptor of IL-4 and IL-13 directly counters that pathway.

“The current treatments are [proton pump inhibitors], steroids, or diet – a good proportion of patients don’t respond to them. And they’re also not targeted,” Evan Dellon, MD, professor of medicine and epidemiology at the University of North Carolina at Chapel Hill, said in an interview. Dr. Dellon presented the research at the annual meeting of the American College of Gastroenterology.

“The bottom line is that people who responded up front to dupilumab maintain that response to a year, and the people on placebo gained a similar response as the people who were treated. It looked good. It was histologic, symptomatic, and endoscopic outcomes,” said Dr. Dellon.

Many of the patients in the new study were steroid refractory, making it a difficult population to treat, according to Dr. Dellon. “You can’t compare to the steroid-treated patients, but the 6-month data showed about a 60% response rate histologically, which is right up there with where steroids and diet are for easier to treat patients. So the fact that it’s a harder to treat cohort is pretty impressive from that standpoint,” said Dr. Dellon.

Data from the first 24 weeks was previously reported at UEG Week 2020 and showed that dupilumab outperformed placebo in EoE patients aged 12 years and older, with dupilumab producing better outcomes in peak esophageal intraepithelial eosinophil count and change in Dysphagia Symptom Questionnaire (DSQ) Score at 24 weeks.

At ACG 2021, Dr. Dellon reported on 52-week results, where all patients from both treated and placebo groups received dupilumab after the initial 24-week phase. Dupilumab reduced dysphagia symptoms as measured by the absolute change in DSQ score at 24 weeks (–21.9 vs. –9.6; P < .001). At 52 weeks, the dupilumab group showed a change of –23.4 from the start of the study, and the placebo-to-dupilumab group had a DSQ score change of –21.7. Dupilumab also led to a greater percentage reduction in DSQ score by 24 weeks (69.2% versus 31.7%; P < .001); at 52 weeks, the dupilumab group had a 75.9% reduction and the placebo-to-dupilumab group had a 65.9% reduction (no significant difference).

The dupilumab group had a greater proportion of patients who achieved peak esophageal eosinophil count of 6 eosinophils or less per high power field at 24 weeks (59.5% vs. 5.1%); at 52 weeks, 55.9% had achieved this measure, versus 60.0% of the placebo-to-dupilumab group. At 24 weeks, the dupilumab group had a 71.2% reduction in peak eosinophil count from baseline versus –3.0% in placebo (P < .001). At week 52, the reductions were 88.6% and 83.8%, respectively.

Histology features were improved with dupilumab. At week 24, the absolute change in histology scoring system mean grade score (histologic severity) from initial baseline was greater in the dupilumab group (least squares mean, –0.761 vs. –0.001; P < .001). The improvement continued at week 52 (LS mean, –0.87) and occurred in the placebo-to-dupilumab group (LS mean, –0.87). The dupilumab group had a greater absolute change in mean stage score at 24 weeks (histologic extent, LS mean, –0.753 vs. –0.012; P < .001) and 52 weeks (LS mean, –0.89), while the placebo-to-dupilumab group achieved a similar change at 52 weeks (LS mean, –0.87).

Endoscopic features improved in the dupilumab group as measured by endoscopic reference score at 24 weeks (LS mean, –3.2 versus –0.3; P <.001) and at 52 weeks (LS mean, –4.1). The placebo-to-dupilumab group had a similar outcome at 52 weeks (LS mean, –3.9).

Dupilumab was well tolerated, with the only significant difference in treatment-emergent adverse events being injection-site reactions and injection-site erythema.

“I thought the data was really impressive and compelling,” said Amy Oxentenko, MD, chair of medicine at the Mayo Clinic in Phoenix, who comoderated the session. “It’d be nice to have something like this that is a targeted therapy that clearly shows improvement in not only some of the symptoms and histology, but also having an impact possibly on that fibrotic piece, which I think is really the area of morbidity in these patients long term.”

If approved, dupilumab could improve compliance among patients, who sometimes struggle with taking topical steroids properly, said comoderator David Hass, MD, who is an associate clinical professor at Yale University, New Haven, Conn. He also agreed that the potential for remodeling would be a significant benefit over steroids.

One concern with dupilumab would be any potential for immune suppression. “It’s always something to think about,” Dr. Hass said.

LIBERTY EoE TREET was funded by Sanofi and Regeneron. Dr. Dellon has consulted and received research support from numerous pharmaceutical companies. Dr. Oxentenko and Dr. Hass have no relevant financial disclosures.

This article was updated Nov. 4, 2021.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

Using stool samples to test for Helicobacter pylori antibiotic resistance provides highly similar results to those of gastric biopsy samples, which suggests that stool testing may be a safer, more convenient, and more cost-effective option, according to investigators.

sgame/thinkstockphotos.com

Head-to-head testing for resistance-associated mutations using next-generation sequencing (NGS) showed 92% concordance between the two sample types, with 100% technical success among polymerase chain reaction (PCR)–positive stool samples, lead author Steven Moss, MD, of Brown University, Providence, R.I., and colleagues reported.

“H. pylori eradication rates have declined largely due to rising antimicrobial resistance worldwide,” Dr. Moss said at the annual meeting of the American College of Gastroenterology. “There is therefore a need for rapid, accurate, reliable antibiotic resistance testing.”

According to Dr. Moss, molecular resistance testing of gastric biopsies yields similar results to culture-based testing of gastric biopsies, but endoscopic sample collection remains inconvenient and relatively costly, so “it is not commonly performed in many GI practices.

“Whether reliable resistance testing by NGS is possible from stool samples remains unclear,” Dr. Moss said.

To explore this possibility, Dr. Moss and colleagues recruited 262 patients scheduled for upper endoscopy at four sites in the United States. From each patient, two gastric biopsies were taken, and within 2 weeks of the procedure, prior to starting anti–H. pylori therapy, one stool sample was collected.

For gastric biopsy samples, H. pylori positivity was confirmed by PCR, whereas positivity in stool samples was confirmed by both fecal antigen testing and PCR. After confirmation, NGS was conducted, with screening for resistance-associated mutations to six commonly used antibiotics: clarithromycin, levofloxacin, metronidazole, tetracycline, amoxicillin, and rifabutin.

Out of 262 patients, 73 tested positive for H. pylori via stool testing; however, 2 of these patients had inadequate gastric DNA for analysis, leaving 71 patients in the evaluable dataset. Within this group, samples from 50 patients (70.4%) had at least one resistance-association mutation.

Among all 71 individuals, 65 patients (91.5%) had fully concordant results between the two sample types. In four out of the six discordant cases, there was only one difference in antibiotic-associated mutations. Concordance ranged from 89% for metronidazole mutations to 100% for tetracycline, amoxicillin, and rifabutin mutations.

“It is now possible to rapidly obtain susceptibility data without endoscopy,” Dr. Moss concluded. “Using NGS to determine H. pylori antibiotic resistance using stool obviates the cost, inconvenience, and risks of endoscopy resistance profiling.”

Dr. Moss noted that the cost of the stool-based test, through study sponsor American Molecular Laboratories, is about $450, and that the company is “working with various insurance companies to try to get [the test] reimbursed.”

For cases of H. pylori infection without resistance testing results, Dr. Moss recommended first-line treatment with quadruple bismuth–based therapy; however, he noted that “most gastroenterologists, in all kinds of practice, are not measuring their eradication success rate ... so it’s really difficult to know if your best guess is really the appropriate treatment.”

According to Lukasz Kwapisz, MD, of Baylor College of Medicine, Houston, the concordance results are “encouraging,” and suggest that stool-based testing “could be much easier for the patient and the clinician” to find ways to eradicate H. pylori infection.

Dr. Kwapisz predicted that it will take additional successful studies, as well as real-world data, to convert clinicians to the new approach. He suggested that the transition may be gradual, like the adoption of fecal calprotectin testing.

“I don’t know if it’s one singular defining study that will tell you: ‘Okay, we all have to use this [stool-based resistance testing],’ ” he said. “It kind of happens over time – over a 2- or 3-year stretch, I would think, with positive results.”

The study was supported by American Molecular Labs. The investigators disclosed additional relationships with Takeda, Phathom, and Redhill. Dr. Kwapisz reported no conflicts of interest.

Combinations of abnormal pH-impedance metrics better predicted nonresponse to proton pump inhibitor therapy, as well as benefit of treatment escalation, than individual metrics in patients with gastroesophageal reflux disease (GERD) on twice-daily PPI.

The researchers found a higher proportion of nonresponders to PPI in a group of patients that had combinations of abnormal reflux burden, characterized as acid exposure time greater than 4%, more than 80 reflux episodes, and/or mean nocturnal baseline impedance (MNBI) less than 1,500 ohms, with 85% of these patients improving following initiation of invasive GERD management such as antireflux surgery or magnetic sphincter augmentation.

Not only does the combination of metrics offer more value in identifying responders to PPI than individual metrics, but the combination also offer greater value in “subsequently predicting response to escalation of antireflux management,” study authors C. Prakash Gyawali, MD, of Washington University, St. Louis, and colleagues wrote in Gastroenterology.

Currently in question is the applicability of thresholds for metrics from pH impedance monitoring for studies performed on PPI. According to Dr. Gyawali and colleagues, thresholds from the Lyon Consensus may be too high and likewise lack optimal sensitivity for detecting refractory acid burden in patients on PPI, while thresholds based on pH-metry alone, as reported in other publications, may also lack specificity.

To determine which metrics from “on PPI” pH impedance studies predict escalation therapy needs, the researchers analyzed deidentified pH impedance studies performed in healthy volunteers (n=66; median age, 37.5 years) and patients with GERD (n = 43; median age, 57.0 years); both groups were on twice-daily PPI. The investigators compared median values for pH impedance metrics between healthy volunteers and patients with proven GERD using validated measures.

Data were included from a total of three groups: tracings from European and North American healthy volunteers who received twice-daily PPI for 5-7 days; tracings from European patients with heartburn-predominant proven GERD with prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI; and tracings from a cohort of patients with regurgitation-predominant, proven GERD and prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI.

A improvement in heartburn of at least 50%, as recorded on 4-point Likert-type scales, defined PPI responders and improvements following antireflux surgery in the European comparison group. Additionally, an improvement of at least 50% on the GERD Health-Related Quality of Life scale also characterized PPI responders and improvements following magnetic sphincter augmentation in the North American comparison group.

There was no significant difference between PPI responders and nonresponders in terms of individual conventional and novel reflux metrics. The combinations of metrics associated with abnormal reflux burden and abnormal mucosal integrity (acid exposure time >4%, >80 reflux episodes, and MNBI <1,500 ohms) were observed in 32.6% of patients with heartburn and 40.5% of patients with regurgitation-predominant GERD, but no healthy volunteers. The combinations were also observed in 57.1% and 82.4% of nonresponders, respectively.

The authors defined a borderline category (acid exposure time, >0.5% but <4%; >40 but <80 reflux episodes), which accounted for 32.6% of patients with heartburn-predominant GERD and 50% of those regurgitation-predominant GERD. Nonresponse among these borderline cases was identified in 28.6% and 81%, respectively.

“Performance characteristics of the presence of abnormal reflux burden and/or abnormal mucosal integrity in predicting PPI nonresponse consisted of sensitivity, 0.50; specificity, 0.71; and AUC, 0.59 (P = .15),” the authors explained. “Performance characteristics of abnormal and borderline reflux burden categories together in predicting PPI nonresponse consisted of sensitivity, 0.86; specificity, 0.36; and AUC, 0.62 (P = .07).”

Limitations of this study included its retrospective nature, small sample sizes for the healthy volunteer and GERD populations, and the lack of data on relevant clinical information, including body mass index, dietary patterns, and PPI types and doses. Additionally, the findings may lack generalizability because of the inclusion of only patients with GERD who underwent surgical management.

Despite these limitations, the researchers wrote that the findings and identified “thresholds will be useful in planning prospective outcome studies to conclusively determine when to escalate antireflux therapy when GERD symptoms persist despite bid PPI therapy.”

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study.

Combinations of abnormal pH-impedance metrics better predicted nonresponse to proton pump inhibitor therapy, as well as benefit of treatment escalation, than individual metrics in patients with gastroesophageal reflux disease (GERD) on twice-daily PPI.

The researchers found a higher proportion of nonresponders to PPI in a group of patients that had combinations of abnormal reflux burden, characterized as acid exposure time greater than 4%, more than 80 reflux episodes, and/or mean nocturnal baseline impedance (MNBI) less than 1,500 ohms, with 85% of these patients improving following initiation of invasive GERD management such as antireflux surgery or magnetic sphincter augmentation.

Not only does the combination of metrics offer more value in identifying responders to PPI than individual metrics, but the combination also offer greater value in “subsequently predicting response to escalation of antireflux management,” study authors C. Prakash Gyawali, MD, of Washington University, St. Louis, and colleagues wrote in Gastroenterology.

Currently in question is the applicability of thresholds for metrics from pH impedance monitoring for studies performed on PPI. According to Dr. Gyawali and colleagues, thresholds from the Lyon Consensus may be too high and likewise lack optimal sensitivity for detecting refractory acid burden in patients on PPI, while thresholds based on pH-metry alone, as reported in other publications, may also lack specificity.

To determine which metrics from “on PPI” pH impedance studies predict escalation therapy needs, the researchers analyzed deidentified pH impedance studies performed in healthy volunteers (n=66; median age, 37.5 years) and patients with GERD (n = 43; median age, 57.0 years); both groups were on twice-daily PPI. The investigators compared median values for pH impedance metrics between healthy volunteers and patients with proven GERD using validated measures.

Data were included from a total of three groups: tracings from European and North American healthy volunteers who received twice-daily PPI for 5-7 days; tracings from European patients with heartburn-predominant proven GERD with prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI; and tracings from a cohort of patients with regurgitation-predominant, proven GERD and prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI.

A improvement in heartburn of at least 50%, as recorded on 4-point Likert-type scales, defined PPI responders and improvements following antireflux surgery in the European comparison group. Additionally, an improvement of at least 50% on the GERD Health-Related Quality of Life scale also characterized PPI responders and improvements following magnetic sphincter augmentation in the North American comparison group.

There was no significant difference between PPI responders and nonresponders in terms of individual conventional and novel reflux metrics. The combinations of metrics associated with abnormal reflux burden and abnormal mucosal integrity (acid exposure time >4%, >80 reflux episodes, and MNBI <1,500 ohms) were observed in 32.6% of patients with heartburn and 40.5% of patients with regurgitation-predominant GERD, but no healthy volunteers. The combinations were also observed in 57.1% and 82.4% of nonresponders, respectively.

The authors defined a borderline category (acid exposure time, >0.5% but <4%; >40 but <80 reflux episodes), which accounted for 32.6% of patients with heartburn-predominant GERD and 50% of those regurgitation-predominant GERD. Nonresponse among these borderline cases was identified in 28.6% and 81%, respectively.

“Performance characteristics of the presence of abnormal reflux burden and/or abnormal mucosal integrity in predicting PPI nonresponse consisted of sensitivity, 0.50; specificity, 0.71; and AUC, 0.59 (P = .15),” the authors explained. “Performance characteristics of abnormal and borderline reflux burden categories together in predicting PPI nonresponse consisted of sensitivity, 0.86; specificity, 0.36; and AUC, 0.62 (P = .07).”

Limitations of this study included its retrospective nature, small sample sizes for the healthy volunteer and GERD populations, and the lack of data on relevant clinical information, including body mass index, dietary patterns, and PPI types and doses. Additionally, the findings may lack generalizability because of the inclusion of only patients with GERD who underwent surgical management.

Despite these limitations, the researchers wrote that the findings and identified “thresholds will be useful in planning prospective outcome studies to conclusively determine when to escalate antireflux therapy when GERD symptoms persist despite bid PPI therapy.”

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study.

Combinations of abnormal pH-impedance metrics better predicted nonresponse to proton pump inhibitor therapy, as well as benefit of treatment escalation, than individual metrics in patients with gastroesophageal reflux disease (GERD) on twice-daily PPI.

The researchers found a higher proportion of nonresponders to PPI in a group of patients that had combinations of abnormal reflux burden, characterized as acid exposure time greater than 4%, more than 80 reflux episodes, and/or mean nocturnal baseline impedance (MNBI) less than 1,500 ohms, with 85% of these patients improving following initiation of invasive GERD management such as antireflux surgery or magnetic sphincter augmentation.

Not only does the combination of metrics offer more value in identifying responders to PPI than individual metrics, but the combination also offer greater value in “subsequently predicting response to escalation of antireflux management,” study authors C. Prakash Gyawali, MD, of Washington University, St. Louis, and colleagues wrote in Gastroenterology.

Currently in question is the applicability of thresholds for metrics from pH impedance monitoring for studies performed on PPI. According to Dr. Gyawali and colleagues, thresholds from the Lyon Consensus may be too high and likewise lack optimal sensitivity for detecting refractory acid burden in patients on PPI, while thresholds based on pH-metry alone, as reported in other publications, may also lack specificity.

To determine which metrics from “on PPI” pH impedance studies predict escalation therapy needs, the researchers analyzed deidentified pH impedance studies performed in healthy volunteers (n=66; median age, 37.5 years) and patients with GERD (n = 43; median age, 57.0 years); both groups were on twice-daily PPI. The investigators compared median values for pH impedance metrics between healthy volunteers and patients with proven GERD using validated measures.

Data were included from a total of three groups: tracings from European and North American healthy volunteers who received twice-daily PPI for 5-7 days; tracings from European patients with heartburn-predominant proven GERD with prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI; and tracings from a cohort of patients with regurgitation-predominant, proven GERD and prior abnormal reflux monitoring off PPI who subsequently received twice-daily PPI.

A improvement in heartburn of at least 50%, as recorded on 4-point Likert-type scales, defined PPI responders and improvements following antireflux surgery in the European comparison group. Additionally, an improvement of at least 50% on the GERD Health-Related Quality of Life scale also characterized PPI responders and improvements following magnetic sphincter augmentation in the North American comparison group.

There was no significant difference between PPI responders and nonresponders in terms of individual conventional and novel reflux metrics. The combinations of metrics associated with abnormal reflux burden and abnormal mucosal integrity (acid exposure time >4%, >80 reflux episodes, and MNBI <1,500 ohms) were observed in 32.6% of patients with heartburn and 40.5% of patients with regurgitation-predominant GERD, but no healthy volunteers. The combinations were also observed in 57.1% and 82.4% of nonresponders, respectively.

The authors defined a borderline category (acid exposure time, >0.5% but <4%; >40 but <80 reflux episodes), which accounted for 32.6% of patients with heartburn-predominant GERD and 50% of those regurgitation-predominant GERD. Nonresponse among these borderline cases was identified in 28.6% and 81%, respectively.

“Performance characteristics of the presence of abnormal reflux burden and/or abnormal mucosal integrity in predicting PPI nonresponse consisted of sensitivity, 0.50; specificity, 0.71; and AUC, 0.59 (P = .15),” the authors explained. “Performance characteristics of abnormal and borderline reflux burden categories together in predicting PPI nonresponse consisted of sensitivity, 0.86; specificity, 0.36; and AUC, 0.62 (P = .07).”

Limitations of this study included its retrospective nature, small sample sizes for the healthy volunteer and GERD populations, and the lack of data on relevant clinical information, including body mass index, dietary patterns, and PPI types and doses. Additionally, the findings may lack generalizability because of the inclusion of only patients with GERD who underwent surgical management.

Despite these limitations, the researchers wrote that the findings and identified “thresholds will be useful in planning prospective outcome studies to conclusively determine when to escalate antireflux therapy when GERD symptoms persist despite bid PPI therapy.”

The study researchers reported conflicts of interest with several pharmaceutical companies. No funding was reported for the study.

A study that compared three types of direct oral anticoagulants (DOACs) found that rivaroxaban was associated with a much higher risk of overall and major gastrointestinal bleeding than apixaban or dabigatran.

The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.

DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.

These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,

Daily dosage may exacerbate risk

Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.

Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.

Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.

The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.

Overall, the study cohort was small, compared with previous registry studies.

Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
 

Clinicians should consider location of bleeding

Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.

“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.

“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
 

Other studies yield similar results

Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.

Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.

A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.

“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.

“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.

The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.

A study that compared three types of direct oral anticoagulants (DOACs) found that rivaroxaban was associated with a much higher risk of overall and major gastrointestinal bleeding than apixaban or dabigatran.

The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.

DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.

These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,

Daily dosage may exacerbate risk

Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.

Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.

Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.

The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.

Overall, the study cohort was small, compared with previous registry studies.

Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
 

Clinicians should consider location of bleeding

Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.

“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.

“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
 

Other studies yield similar results

Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.

Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.

A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.

“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.

“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.

The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.

A study that compared three types of direct oral anticoagulants (DOACs) found that rivaroxaban was associated with a much higher risk of overall and major gastrointestinal bleeding than apixaban or dabigatran.

The results, which were published in the Annals of Internal Medicine, could help guide DOAC selection for high-risk groups with a prior history of peptic ulcer disease or major GI bleeding, said lead study authors Arnar Bragi Ingason, MD and Einar S. Björnsson, MD, PhD, in an email.

DOACs treat conditions such as atrial fibrillation, venous thromboembolism, and ischemic stroke and are known to cause GI bleeding. Previous studies have suggested that rivaroxaban poses a higher GI-bleeding risk than other DOACs.

These studies, which used large administrative databases, “had an inherent risk of selection bias due to insurance status, age, and comorbidities due to their origin from insurance/administrative databases. In addition, they lacked phenotypic details on GI bleeding events,” said Dr. Björnsson and Dr. Ingason, who are both of Landspitali University Hospital, Reykjavik, Iceland,

Daily dosage may exacerbate risk

Rivaroxaban is administered as a single daily dose, compared with apixaban’s and dabigatran’s twice-daily regimens. “We hypothesized that this may lead to a greater variance in drug plasma concentration, making these patients more susceptible to GI bleeding,” the lead authors said.

Using data from the Icelandic Medicine Registry, a national database of outpatient prescription information, they compared rates of GI bleeding among new users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019. Overall, 5,868 patients receiving one of the DOACs took part in the study. Among these participants, 3,217 received rivaroxaban, 2,157 received apixaban, and 494 received dabigatran. The researchers used inverse probability weighting, Kaplan–Meier survival estimates, and Cox regression to compare GI bleeding.

Compared with dabigatran, rivaroxaban was associated with a 63%-104% higher overall risk for GI bleeding and 39%-95% higher risk for major GI bleeding. Rivaroxaban also had a 40%-42% higher overall risk for GI bleeding and 49%-50% higher risk for major GI bleeding, compared with apixaban.

The investigators were surprised by the low rate of upper GI bleeding for dabigatran, compared with the other two drugs. “However, these results must be interpreted in the context that the dabigatran group was relatively small,” said Dr. Björnsson and Dr. Ingason via email.

Overall, the study cohort was small, compared with previous registry studies.

Investigators also did not account for account for socioeconomic status or lifestyle factors, such as alcohol consumption or smoking. “However, because the cost of all DOACs is similar in Iceland, selection bias due to socioeconomic status is unlikely,” the investigators reported in their paper. “We are currently working on comparing the rates of thromboembolisms and overall major bleeding events between the drugs,” the lead authors said.
 

Clinicians should consider location of bleeding

Though retrospective, the study by Ingason et. al. “is likely as close as is feasible to a randomized trial as is possible,” said Don C. Rockey, MD, a professor of medicine at the Medical University of South Carolina, Charleston, in an interview.

“From the clinician’s perspective, it is important to take away that there may be differences among the DOACs in terms of where in the GI tract the bleeding occurs,” said Dr. Rockey. In the study, the greatest differences appeared to be in the upper GI tract, with rivaroxaban outpacing apixaban and dabigatran. In patients who are at risk for upper GI bleeding, it may be reasonable to consider use of dabigatran or apixaban, he suggested.

“A limitation of the study is that it is likely underpowered overall,” said Dr. Rockey. It also wasn’t clear how many deaths occurred either directly from GI bleeding or as a complication of GI bleeding, he said.The study also didn’t differentiate major bleeding among DOACs specifically in the upper or lower GI tract, Dr. Rockey added.
 

Other studies yield similar results

Dr. Ingason and Dr. Björnsson said their work complements previous studies, and Neena S. Abraham, MD, MSc , who has conducted a similar investigation to the new study, agreed with that statement.

Data from the last 4 years overwhelmingly show that rivaroxaban is most likely to cause GI bleeding, said Dr. Abraham, professor of medicine and a consultant with Mayo Clinic’s division of gastroenterology and hepatology, in an interview.

A comparative safety study Dr. Abraham coauthored in 2017 of rivaroxaban, apixaban, and dabigatran in a much larger U.S. cohort of 372,380 patients revealed that rivaroxaban had the worst GI bleeding profile. Apixaban was 66% safer than rivaroxaban and 64% safer than dabigatran to prevent gastrointestinal bleeding.

“I believe our group was the first to conduct this study and show clinically significant differences in GI safety of the available direct oral anticoagulants,” she said. Other investigators have since published similar results, and the topic of the new study needs no further investigation, according to Dr. Abraham.

“It is time for physicians to choose a better choice when prescribing a direct oral anticoagulant to their atrial fibrillation patients, and that choice is not rivaroxaban,” she said.

The Icelandic Centre for Research and the Landspítali University Hospital Research Fund provided funds for this study. Dr. Ingason, Dr. Björnsson, Dr. Rockey, and Dr. Abraham reported no disclosures.

Evaluation of patients with extraesophageal symptoms of reflux is a challenging area in gastroesophageal reflux disease (GERD). Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus. 

In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients.  Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories.  Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation.  The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.  

Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing.  It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play. 

Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.”  They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.

Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

Evaluation of patients with extraesophageal symptoms of reflux is a challenging area in gastroesophageal reflux disease (GERD). Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus. 

In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients.  Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories.  Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation.  The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.  

Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing.  It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play. 

Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.”  They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.

Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.

Evaluation of patients with extraesophageal symptoms of reflux is a challenging area in gastroesophageal reflux disease (GERD). Patients often present with symptoms that are not classic for reflux such as chronic cough, worsening asthma, sore throat, or globus. 

In the upper GI section of the postgraduate course program, Rena Yadlapati, MD, and C. Prakash Gyawali, MD, MRCP, educated us about optimal strategies for diagnosis and treatment of this difficult group of patients.  Dr. Gyawali reminded us of risk stratification of patients into those with high or low likelihood of reflux as contributing etiology for patients with suspected extraesophageal reflux. Dr. Yadlapti reviewed the utility of the HASBEER score in stratifying patients into these two risk categories.  Patients with known reflux at baseline and/or if they have classic symptoms of reflux in addition to extraesophageal symptoms may be at higher likelihood of having abnormal esophageal acid exposure than those without classic heartburn and/or regurgitation.  The low-risk group may then benefit from diagnostic testing off PPI therapy (either impedance/pH monitoring or wireless pH testing), whereas those in the high-risk group for reflux may undergo impedance pH testing on PPI therapy to ensure control of reflux while on therapy.  

Dr. Yadlapati also updated the audience about lack of robust data to suggest clinical utility for oropharyngeal pH test or salivary pepsin assay testing.  It was generally agreed on that the majority of patients who do not respond to aggressive acid suppressive therapy likely do not have reflux related extraesophageal symptoms and alternative etiologies may be at play. 

Finally, both investigators outlined the importance of neuromodulation in those whose symptoms may be due to “irritable larynx.”  They emphasized the role of tricyclics as well as gabapentin as off label uses for patients who have normal reflux testing and continue to have chronic cough or globus sensation.

Michael F. Vaezi, MD, PhD, MSc, is an associate chief and a clinical director of the division of gastroenterology, hepatology, and nutrition and director of the Clinical Research and Center for Esophageal Disorders at Vanderbilt University, Nashville, Tenn. He reports consulting for Phathom, Ironwood, Diversatek, Isothrive, and Medtronic. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2021.