Upper GI Tract

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Almost half of adult patients with eosinophilic esophagitis (EoE) reported poor adherence to long-term medical and dietary therapy, with age younger than 40 years and low necessity beliefs being the strongest predictors, a new study finds.

Clinicians need to spend more time discussing the need for EoE therapy with their patients, especially if they are younger, according to lead author Maria L. Haasnoot, MD, of Amsterdam University Medical Center (UMC), the Netherlands, and colleagues.

“Chronic treatment is necessary to maintain suppression of the inflammation and prevent negative outcomes in the long-term,” they write.

Until the recent approval of dupilumab (Dupixent) by the U.S. Food and Drug Administration, patients with EoE relied upon off-label options, including proton pump inhibitors and swallowed topical steroids, as well as dietary interventions for ongoing suppression of inflammation. But only about 1 in 6 patients achieve complete remission at 5 years, according to Dr. Haasnoot and colleagues.

“It is uncertain to what degree limited adherence to treatment [plays] a role in the limited long-term effects of treatment,” they write.

The findings were published online in American Journal of Gastroenterology.
 

Addressing a knowledge gap

The cross-sectional study involved 177 adult patients with EoE treated at Amsterdam UMC, who were prescribed dietary or medical maintenance therapy. Of note, some patients were treated with budesonide, which is approved for EoE in Europe but not in the United States.

Median participant age was 43 years, with a male-skewed distribution (71% men). Patients had been on EoE treatment for 2-6 years. Most (76%) were on medical treatments. Nearly half were on diets that avoided one to five food groups, with some on both medical treatments and elimination diets.

Using a link sent by mail, participants completed the online Medication Adherence Rating Scale, along with several other questionnaires, such as the Beliefs about Medicine Questionnaire, to measure secondary outcomes, including a patient’s view of how necessary or disruptive maintenance therapy is in their life.

The overall prevalence of poor adherence to therapy was high (41.8%), including a nonsignificant difference in adherence between medical and dietary therapies.

“It might come as a surprise that dietary-treated patients are certainly not less adherent to treatment than medically treated patients,” the authors write, noting that the opposite is usually true.

Multivariate logistic regression showed that patients younger than 40 years were more than twice as likely to be poorly adherent (odds ratio, 2.571; 95% confidence interval, 1.195-5.532). Those with low necessity beliefs were more than four times as likely to be poorly adherent (OR, 4.423; 95% CI, 2.169-9.016). Other factors linked to poor adherence were patients with longer disease duration and more severe symptoms.

“Clinicians should pay more attention to treatment adherence, particularly in younger patients,” the authors conclude. “The necessity of treatment should be actively discussed, and efforts should be done to take doubts away, as this may improve treatment adherence and subsequently may improve treatment effects and long-term outcomes.”
 

More patient education needed

According to Jennifer L. Horsley-Silva, MD, of Mayo Clinic, Scottsdale, Ariz., “This study is important, as it is one of the first studies to investigate the rate of treatment adherence in EoE patients and attempts to identify factors associated with adherence both in medically and dietary treated patients.”

Dr. Horsley-Silva commented that the findings align with recent research she and her colleagues conducted at the Mayo Clinic, where few patients successfully completed a six-food elimination diet, even when paired with a dietitian. As with the present study, success trended lower among younger adults. “These findings highlight the need for physicians treating EoE to motivate all patients, but especially younger patients, by discussing disease pathophysiology and explaining the reason for maintenance treatment early on,” Dr. Horsley-Silva said.

Conversations should also address the discordance between symptoms and histologic disease, patient doubts and concerns, and other barriers to adherence, she noted.

“Shared decisionmaking is of utmost importance when deciding upon a maintenance treatment strategy and should be readdressed continually,” she added.

Gary W. Falk, MD, of Penn Medicine, Philadelphia, said that patients with EoE may be poorly adherent because therapies tend to be complicated and people often forget to take their medications, especially when their symptoms improve, even though this is a poor indicator of underlying disease. The discordance between symptoms and histology is “not commonly appreciated by the EoE GI community,” he noted.

Patients may benefit from knowing that untreated or undertreated EoE increases the risk for strictures and stenoses, need for dilation, and frequency of food bolus impactions, Dr. Falk said.

“The other thing we know is that once someone is induced into remission, and they stay on therapy ... long-term remission can be maintained,” he added.
 

The impact of Dupilumab

John Leung, MD, of Boston Food Allergy Center, also cited the complexities of EoE therapies as reason for poor adherence, though he believes this paradigm will shift now that dupilumab has been approved. Dupilumab injections are “just once a week, so it’s much easier in terms of frequency,” Dr. Leung said. “I would expect that the compliance [for dupilumab] will be better” than for older therapies.

Dr. Leung, who helped conduct the dupilumab clinical trials contributing to its approval for EoE and receives speaking honoraria from manufacturer Regeneron/Sanofi, said that dupilumab also overcomes the challenges with elimination diets while offering relief for concomitant conditions, such as “asthma, eczema, food allergies, and seasonal allergies.”

But Dr. Falk, who also worked on the dupilumab clinical trials, said the situation is “not straightforward,” even with FDA approval.

“There are going to be significant costs with [prescribing dupilumab], because it’s a biologic,” Dr. Falk said.

Dr. Falk also pointed out that prior authorization will be required, and until more studies can be conducted, the true impact of once-weekly dosing versus daily dosing remains unknown.

“I would say [dupilumab] has the potential to improve adherence, but we need to see if that’s going to be the case or not,” Dr. Falk said.

The authors disclosed relationships with Dr. Falk Pharma, AstraZeneca, and Sanofi/Regeneron (the manufacturers of Dupixent [dupilumab]), among others. Dr. Horsley-Silva, Dr. Falk, and Dr. Leung conducted clinical trials for dupilumab on behalf of Sanofi/Regeneron, with Dr. Leung also disclosing speaking honoraria from Sanofi/Regeneron. Dr. Horsley-Silva has acted as a clinical trial site principal investigator for Allakos and Celgene/Bristol-Myers Squibb.

A version of this article first appeared on Medscape.com.

Fifteen years is a lifetime for the advancement of medical research. This seems particularly true for upper GI tract disorders.

In 2007, eosinophilic esophagitis was a rare disease; limited clinical data were available describing the symptoms, demographic characteristics, and endoscopic findings. Treatment was guided mostly by uncontrolled patient series for topical steroids and comprehensive diet exclusion therapy. Today, the molecular, genetic, and evolving microbiome’s contributions to EoE are being elucidated. EoE is recognized as one of the most common diseases in our practice, and rigorously performed controlled trials of steroids and biologics (including Food and Drug Administration–approved dupilumab) guide our treatment. Diet has also become easier with the identification of a single food antigen as the cause in 40% of EoE patients. The most pressing need is for a test that’s reliable and less invasive than endoscopy to assess and monitor treatment.

Dr. Katzka is professor of medicine at Columbia University, New York. He reports consulting for Takeda and Celgene.

This article was updated July 7, 2022.

Fifteen years is a lifetime for the advancement of medical research. This seems particularly true for upper GI tract disorders.

In 2007, eosinophilic esophagitis was a rare disease; limited clinical data were available describing the symptoms, demographic characteristics, and endoscopic findings. Treatment was guided mostly by uncontrolled patient series for topical steroids and comprehensive diet exclusion therapy. Today, the molecular, genetic, and evolving microbiome’s contributions to EoE are being elucidated. EoE is recognized as one of the most common diseases in our practice, and rigorously performed controlled trials of steroids and biologics (including Food and Drug Administration–approved dupilumab) guide our treatment. Diet has also become easier with the identification of a single food antigen as the cause in 40% of EoE patients. The most pressing need is for a test that’s reliable and less invasive than endoscopy to assess and monitor treatment.

Dr. Katzka is professor of medicine at Columbia University, New York. He reports consulting for Takeda and Celgene.

This article was updated July 7, 2022.

Fifteen years is a lifetime for the advancement of medical research. This seems particularly true for upper GI tract disorders.

In 2007, eosinophilic esophagitis was a rare disease; limited clinical data were available describing the symptoms, demographic characteristics, and endoscopic findings. Treatment was guided mostly by uncontrolled patient series for topical steroids and comprehensive diet exclusion therapy. Today, the molecular, genetic, and evolving microbiome’s contributions to EoE are being elucidated. EoE is recognized as one of the most common diseases in our practice, and rigorously performed controlled trials of steroids and biologics (including Food and Drug Administration–approved dupilumab) guide our treatment. Diet has also become easier with the identification of a single food antigen as the cause in 40% of EoE patients. The most pressing need is for a test that’s reliable and less invasive than endoscopy to assess and monitor treatment.

Dr. Katzka is professor of medicine at Columbia University, New York. He reports consulting for Takeda and Celgene.

This article was updated July 7, 2022.

A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

copyright nebari/Thinkstock

“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

copyright nebari/Thinkstock

“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

A randomized clinical trial indicated that add-on baclofen may be of benefit to patients on adequate doses of proton pump inhibitors (PPI) with refractory gastroesophageal reflux disease (GERD). However, the benefit was limited to a subset of patients with positive symptom association probability (SAP), which was calculated using 24-hour combined multichannel intraluminal impedance and pH monitoring (24h pH-MII).

copyright nebari/Thinkstock

“Empirical add-on therapy with baclofen in GERD patients with persisting typical symptoms in spite of double-dose PPI therapy does not seem justified. The use of baclofen should be limited to patients who display a positive SAP for typical reflux symptoms (heartburn and/or regurgitation) during PPI therapy,” researchers led by Ans Pauwels, PhD, MPharmSc, of the Catholic University of Leuven (Belgium) concluded in Alimentary Pharmacology & Therapeutics.

Asked to comment, Philip Katz, MD, professor of medicine and director of GI Function Laboratories at Weill Cornell Medicine and a co-author of some recent GERD guidelines said, “What it tells me is that baclofen may be useful to a patient population that has an accurate diagnosis of reflux hypersensitivity. The difficulty with this study is that the patients you would expect to be helped by baclofen, which were patients who satisfied the criteria for true GERD, didn’t have any improvement.”

PPIs are effective at reducing acid reflux and promoting esophageal healing in GERD patients, but they have little effect on non-acid reflux. Heartburn is most often tied to acid reflux, but regurgitation occurs with similar frequency during both acid and non-acid episodes.

Up to 50% of patients still have reflux despite PPI treatment, and many of these patients will respond to higher PPI doses. However, those who don’t respond are left with few treatment choices.

Reflux events generally occur during transient lower esophageal sphincter relaxations (TLOSRs), and this mechanism is predominant in mild and moderate GERD. A gamma-aminobutyric acid type B receptor agonist, baclofen reduces TLOSRs and associated reflux episodes following meals. Few studies have examined the clinical potential of baclofen in refractory GERD, and it generally is only used after determining that ongoing weakly acidic reflux is responsible for symptoms, using 24h pH-MII.

The study included about 60 patients who underwent 24-hour monitoring while taking a PPI twice daily. Over a 2-week run-in period, participants filled out daily diaries and were randomized to placebo or baclofen 3 times daily over 4 weeks. The baclofen dose was 5 mg for the first week, then 10 mg for the next 3 weeks.

At the end of treatment, 24h pH-MII was repeated. The researchers found no significant decreases in non-acid reflux events after placebo treatment (corrected P = .74) and a trend towards a reduction following baclofen treatment (corrected P = .12).

Although the results won’t change his practice significantly, Dr. Katz congratulated the authors on the thoroughness of the study. However, he noted that wellbeing is a difficult endpoint to study: “The importance of this study to me is that it confirms that baclofen shouldn’t be used empirically, since there was no improvement in patients who were functional, and it was hard to find improvement in any group. This reinforces the need for a thorough work-up of the patient with GERD.”

The drug also had some tolerability issues: 16% of patients on baclofen discontinued its use because of adverse events such as drowsiness, dizziness, headache, and nausea.

An important limitation of the study is that the researchers recruited patients with persistent GERD symptoms despite use of PPIs. “Calling it refractory GERD is tricky because they didn’t prove they had GERD before they were enrolled in the study. That being said, the researchers did a very rigorous, very careful study to try and find potentially some place that baclofen might benefit patients,” said Dr. Katz.

The authors of the study and Dr. Katz have no relevant financial disclosures.

The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.

The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.

University of North Carolina

How it works

The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.

In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.

Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.

Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.

Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.

Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.

The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.

Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.

“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
 

Simplifying clinical practice

Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.

“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”

Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.

“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”

He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.

“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”

This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.

The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.

This article was updated on June 7, 2022.

The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.

The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.

University of North Carolina

How it works

The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.

In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.

Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.

Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.

Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.

Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.

The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.

Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.

“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
 

Simplifying clinical practice

Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.

“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”

Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.

“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”

He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.

“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”

This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.

The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.

This article was updated on June 7, 2022.

The American Gastroenterological Association has developed a new index to help clinicians gauge the severity of eosinophilic esophagitis (EoE), offering a tool to physicians that experts say has been lacking in the field and should help better guide treatment.

The index – known as I-SEE, for Index of Severity for Eosinophilic Esophagitis – was developed after an exhaustive review of the literature, and allows clinicians to calculate a score based on symptoms, complications, endoscopy findings, and histology. It was published in Gastroenterology and the Journal of Allergy and Clinical Immunology.

University of North Carolina

How it works

The index divides criteria into three main categories: symptoms and complications, inflammatory features, and fibrostenotic features.

In the symptoms and complications category, points are assessed based on whether symptoms are weekly, daily, or several times a day and whether problems such as food impaction or esophageal perforations are present.

Inflammatory features include localized or diffuse edema or furrows on endoscopy and eosinophil counts.

Fibrostenotic scoring items include features such as rings or strictures and how constricting they are, as well as basal zone hyperplasia and lamina propria fibrosis.

Each feature is assigned a score of 1-15. An overall score of 0 points would be considered inactive disease; 1-6 is mildly active disease; 7-14 is moderately active disease; and 15 or more is severely active disease.

Someone with daily symptoms (2 points) and localized edema on endoscopy (1 point) and 15-60 eosinophils per high power field (1 point) would have a total of 4 points and be considered to have mildly active disease. Someone who is 18 years of age or older with daily symptoms (2 points), food impaction with an ED visit (2 points), diffuse edema on endoscopy (2 points), 15-60 eosinophils per high power field (1 point), basal zone hyperplasia (2 points), and rings or strictures on endoscopy that don’t permit passing a standard upper endoscope (15 points), would have 24 points and be considered to have severely active disease.

The index is only just starting to be tested with patient-level data, but the first results are promising, Dr. Dellon said. He hopes incorporating endoscopic and histologic features into the index will lead to wider evaluation of these indicators of severity because they have been shown to be important clinically.

Dr. Dellon said there is a plan to develop an app that will allow the index’s “usability” to be tested across a range of practice settings and disciplines. The index will also be evaluated in existing and prospectively collected datasets.

“This will help us understand the distribution of EoE patient severity in a number of settings, as well as how severity relates to posttreatment outcomes,” he said. “Ultimately, it is possible that I-SEE could be incorporated into electronic medical records systems.”
 

Simplifying clinical practice

Philip Katz, MD, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York, said the index could be a step forward in the care of EoE patients.

“The way all of us make choices for these patients and how we judge where they are in terms of the ‘severity’ of their disease is not ideal, by any means,” he said. “[This] appears to be a strong attempt to simplify what we’re currently doing now and put it all in one place.”

Ease of use will be important and his practice will be evaluating that, he said. He said he hopes that software will make it practical, possibly with the necessary information able to be imported straight from the electronic health record.

“We’ll do our best to use the system data in a way that the authors have suggested,” he said. “Basically, we’ll make our own opinions as data is gathered.”

He recommended that clinicians treating EoE try to use the index and assess its performance on their own, in addition to staying aware of data that’s collected elsewhere in the field. That way, collectively, the tool will have the maximum impact on improving patient care.

“[The researchers who developed the tool] are people who have dedicated a substantial portion of their professional careers to studying this disease and are comfortable that this is a tool that will offer more value than what we’re currently doing,” he said. “Chances are, this will be much better than what we currently have.”

This new tool was developed as part of AGA’s EoE initiative: Eosinophilic Esophagitis: Expand, Optimize, Excel. View additional resources at eoe.gastro.org.

The index was developed as part of a conference that was supported by a grant from Takeda. This conference was also funded in part by the division of intramural research at National Institute of Allergy and Infectious Diseases/National Institutes of Health and supported by CEGIR (U54 AI117804). All activities and products resulting from this conference were independently developed with no involvement or input from the funder. The authors disclosed relationships with various industry entities, including Takeda. None of the other relationships were relevant to this work. Dr. Katz consults with Phathom, Sebela Pharmaceuticals, and AstraZeneca.

This article was updated on June 7, 2022.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

Eosinophilic GI diseases (EGIDs) often overlap with other eosinophil-associated diseases (EADs), which leads to greater health care costs, according to an analysis of the U.S. Optum Clinformatics claims database.

EADs have gained increased attention in recent years. They include eosinophilic esophagitis (EoE), eosinophilic asthma, bullous pemphigoid, eosinophilic granulomatosis with polyangiitis, eosinophilic gastritis/gastroenteritis (EG/EGE), and a subset of non–cystic fibrosis bronchiectasis. All involve infiltration of eosinophils, but the exact immune mechanisms behind them seem to vary and are poorly understood, according to Justin Kwiatek, PharmD, who presented the results at the annual Digestive Disease Week^® (DDW).

“We do know that the suitable course of treatment is dependent on the organs impacted. From this study, we also know that EoE mostly exists on its own, with only a small portion also being diagnosed with asthma, while overlap with other EGIDs tends to be higher. This could be because EoE appears to be pathologically different from other EGIDs in the gastrointestinal tract such as eosinophilic gastritis in the stomach or eosinophilic gastroenteritis in the stomach and small bowel. Eosinophils are not normally present in the esophagus but are often found in the stomach or small bowel without inflammation,” said Dr. Kwiatek, who is senior global medical affairs leader, respiratory & immunology, at AstraZeneca.

The study is important, said Dhyanesh Patel, MD, who was asked to comment on the study. “There’s been a lot of interest in eosinophilic gastrointestinal diseases recently because there is lack of a clear definition. We need to define it better because we need to figure out treatment options for the patients,” said Dr. Patel, who is an assistant professor of medicine at Vanderbilt University, Nashville, Tenn.

“It highlights that a lot of the patients that have one eosinophilic disease might have other concomitant atopic diseases. [It may be that] you can use one drug to treat all of them together, so I think it’s important to have a multidisciplinary approach where you work with an allergist and you work with an immunologist and treat their eosinophilic gastritis and their asthma together with one drug. That may help reduce medication burden,” said Dr. Patel.

The researchers analyzed records from 1,326,645 diagnosed patients with at least one EAD and at least 2 years following treatment. There were 13,872 patients with EoE, 38.4% of whom had at least one overlapping EAD. Of 1,365 patients with EG/EGE, 57.9% had at least one overlapping EAD.

EADs were associated with higher Charlson Comorbidity Index scores and high blood eosinophil levels (≥ 300 cells/mcL) among EoE patients, but not among EG/EGE patients. Within the EoE group, female gender was linked to more EAD comorbidities: 35% of patients with only EoE were female; 45% of patients with one comorbidity were female, as were 55% of those with two comorbidities and 57% of those with three or more comorbidities. There was no such trend among patients with EG/EGE.

Total health care costs were lower in the absence of one overlapping EAD among both EoE ($2,061 vs. $3,766 per patient per month) and EG/EGE patients ($2,860 vs. $4,053). Costs went up with more overlap: $8,572 for EoE and three or more other EADs, and $10,397 for EG/EGE and three or more other EADs. These costs were largely driven by outpatient care.

“The data shows that patients with eosinophilic gastritis and eosinophilic gastroenteritis are more likely to have overlapping eosinophilic conditions, such as asthma. When diagnosing a patient with EG or EGE, it’s important to monitor any new symptoms closely and to educate them about the risk factors. This is particularly true for patients with elevated blood eosinophil counts. Accounting for comorbidities and establishing a treatment plan early can help to manage the higher health care spend for patients with overlapping conditions,” said Dr. Kwiatek.

Dr. Kwiatek is an employee and stockholder of AstraZeneca, which funded the study and developed benralizumab, a drug that has been granted orphan drug status for EG/EGE and EoE. Optum Clinformatics is a longitudinal database of deidentified data formed by UnitedHealth Group. Dr. Patel has no relevant financial disclosures.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

SAN DIEGO – Treatments to eradicate Helicobacter pylori (H. pylori) infections do increase the antibiotic resistance of the gut microbiota, but for only a few months, researchers reported at Digestive Disease Week^® (DDW).

The finding applies similarly to levofloxacin quadruple therapy and bismuth quadruple therapy, both of which are equally efficacious as second-line treatments, said Jyh-Ming Liou, MD, PhD, clinical professor of internal medicine at National Taiwan University in Taipei.

This provides some reassurance that increased use of antibiotics to treat these infections won’t cause long-term disruptions to the patients’ microbiomes, said Dr. Liou.

“Maybe if we have indications for antibiotic treatment, then we don’t worry about the emergence of resistance in our bodies,” he said. “But the accumulation of antibodies in the environment may induce bacteria to mutate, so maybe we still need cautious use of antibiotics.”

H. pylori infections are becoming harder to treat as more strains develop resistance to antibiotics, leading physicians to use regimens with multiple agents. This in turn has raised concerns that gut microbiota could be disrupted, with pathogens potentially developing their own resistance.

To explore these risks, Dr. Liou and colleagues recruited adults whose H. pylori infections were not successfully eradicated.

They randomly assigned 280 patients each to one of two second-line therapies, levofloxacin quadruple or bismuth quadruple. At baseline, the researchers could not find any statistically significant differences in the two groups’ demographics, cigarette and alcohol use, or ulcers, as well as antibiotic resistance in patients’ microbiome between the groups.

Levofloxacin quadruple therapy consisted of esomeprazole 40 mg and amoxicillin 1 g for the first 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for another 7 days (all twice daily).

Bismuth quadruple therapy consisted of esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day, for 10 days.

The researchers collected stool samples at baseline, week 2, week 8, and 1 year after eradication therapy and analyzed them for microbiota diversity and antibiotic susceptibility.

The H. pylori eradication rates were almost the same in the two second-line therapies: 87.9% for levofloxacin quadruple and 87.5% for bismuth quadruple. When they were used as third-line (rescue) therapies, the success rates were also statistically the same, and the cumulative second-line and third-line eradication rate was 95.6% for levofloxacin quadruple and 96.6% for bismuth quadruple.

The two treatments did differ in adverse events with 48.4% for levofloxacin quadruple and 77.3% for bismuth quadruple, which was statistically significant (P < .0001).

After a year, H. pylori reinfected 2.5% of the levofloxacin group and 3% of the bismuth quadruple group.

The researchers used metagenomic sequencing to examine the bacteria in the patients’ microbiome for antibiotic resistance. Using 16S rRNA sequencing, they found that the proportion of genera and species with significant changes in abundance at 2 weeks after treatment compared with baseline was 52.4% for levofloxacin quadruple therapy versus 45.1% for bismuth quadruple therapy.

However, 8 weeks after treatment, the proportion with significant changes had dropped to 5.8% for the levofloxacin group and 21.5% for the bismuth group. And at the end of a year, they had further dropped to 0.9% for the levofloxacin group and 8.4% for the bismuth group.

“It was generally reassuring that, even after giving these combinations of different antibiotics, eventually it doesn’t seem to affect the resistance pattern in bacteria lower down in the gut,” said session moderator Steven Moss, MD, professor of medicine at Brown University in Providence, R.I.

Still, continuing to pile on more and more antibiotics to treat H. pylori infections won’t work forever because H. pylori strains are themselves developing resistance so rapidly, he said. “We’re certainly going to have worse eradications in the future unless we can come up with new tricks.”

A hopeful development are new techniques to test H. pylori for resistance to specific antibiotics before initiating treatment, said Dr. Moss.

Dr. Moss consults with companies developing H. pylori therapies and diagnostics. Dr. Liou reported no relevant financial interests.

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Controversy regarding the purported link between the use of proton pump inhibitors (PPIs) or histamine H₂ receptor antagonists (H2RAs) and risk for dementia continues.

Adding to the “no link” column comes new evidence from a study presented at the annual Digestive Disease Week^® (DDW) .

Among almost 19,000 people, no association was found between the use of these agents and a greater likelihood of incident dementia, Alzheimer’s disease, or cognitive decline in people older than 65 years.

“We found that baseline PPI or H2RA use in older adults was not associated with dementia, with mild cognitive impairment, or declines in cognitive scores over time,” said lead author Raaj Shishir Mehta, MD, a gastroenterology fellow at Massachusetts General Hospital in Boston.

“While deprescribing efforts are important, especially when medications are not indicated, these data provide reassurance about the cognitive impacts of long-term use of PPIs in older adults,” he added.
 

Growing use, growing concern

As PPI use has increased worldwide, so too have concerns over the adverse effects from their long-term use, Dr. Mehta said.

“One particular area of concern, especially among older adults, is the link between long-term PPI use and risk for dementia,” he said.

Igniting the controversy was a February 2016 study published in JAMA Neurology that showed a positive association between PPI use and dementia in residents of Germany aged 75 years and older. Researchers linked PPI use to a 44% increased risk of dementia over 5 years.

The 2016 study was based on claims data, which can introduce “inaccuracy or bias in defining dementia cases,” Dr. Mehta said. He noted that it and other previous studies also were limited by an inability to account for concomitant medications or comorbidities.

To overcome these limitations in their study, Dr. Mehta and colleagues analyzed medication data collected during in-person visits and asked experts to confirm dementia outcomes. The research data come from ASPREE, a large aspirin study of 18,846 people older than 65 years in the United States and Australia. Participants were enrolled from 2010 to 2014. A total of 566 people developed incident dementia during follow-up.

The researchers had data on alcohol consumption and other lifestyle factors, as well as information on comorbidities, hospitalizations, and overall well-being.

“Perhaps the biggest strength of our study is our rigorous neurocognitive assessments,” Dr. Mehta said.

They assessed cognition at baseline and at years 1, 3, 5, and 7 using a battery of tests. An expert panel of neurologists, neuropsychologists, and geriatricians adjudicated cases of dementia, in accordance with DSM-IV criteria. If the diagnosis was unclear, they referred people for additional workup, including neuroimaging.

Cox proportional hazards, regression, and/or mixed effects modeling were used to relate medication use with cognitive scores.

All analyses were adjusted for age, sex, body mass index, alcohol use, family history of dementia, medications, and other medical comorbidities.

At baseline, PPI users were more likely to be White, have fewer years of education, and have higher rates of hypertension, diabetes, and kidney disease. This group also was more likely to be taking five or more medications.
 

Key points

During 80,976 person-years of follow-up, there were 566 incident cases of dementia, including 235 probable cases of Alzheimer’s disease and 331 other dementias.

Baseline PPI use, in comparison with nonuse, was not associated with incident dementia (hazard ratio, 0.86; 95% confidence interval, 0.70-1.05).

“Similarly, when we look specifically at Alzheimer’s disease or mixed types of dementia, we find no association between baseline PPI use and dementia,” Dr. Mehta said.

When they excluded people already taking PPIs at baseline, they found no association between starting PPIs and developing dementia over time.

Secondary aims of the study included looking for a link between PPI use and mild cognitive impairment or significant changes in cognition over time. In both cases, no association emerged. PPI use at baseline also was not associated with cognitive impairment/no dementia (also known as mild cognitive impairment) or with changes in overall cognitive test scores over time.

To determine whether any association could be a class effect of acid suppression medication, they assessed use of H2RA medications and development of incident dementia. Again, the researchers found no link.

A diverse multinational population from urban and rural areas was a strength of the study, as was the “very rigorous cognitive testing with expert adjudication of our endpoints,” Dr. Mehta said. In addition, fewer than 5% of patients were lost to follow-up.

In terms of limitations, this was an observational study “so residual confounding is always possible,” he added. “But I’ll emphasize that we are among the largest studies to date with wealth of covariates.”
 

Why the different findings?

The study was “really well done,” session moderator Paul Moayyedi, MD, said during the Q&A session at DDW 2022.

Dr. Moayyedi, a professor of medicine at McMaster University, Hamilton, Ont., asked Dr. Mehta why he “found absolutely no signal, whereas the German study did.”

“It’s a good question,” Dr. Mehta responded. “If you look across the board, there have been conflicting results.”

The disparity could be related to how researchers conducting claims data studies classify dementia, he noted.

“If you look at the nitty-gritty details over 5 years, almost 40% of participants [in those studies] end up with a diagnosis of dementia, which is quite high,” Dr. Mehta said. “That raises questions about whether the diagnosis of dementia is truly accurate.”

Dr. Mehta and Dr. Moayyedi reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved dupilumab (Dupixent, Regeneron) to treat eosinophilic esophagitis (EoE) in adults and children aged 12 years and older weighing at least 40 kg.

EoE is a chronic inflammatory disorder driven by type 2 inflammation that damages the esophagus and causes difficulty swallowing and eating.

Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. It’s the first drug to be approved by the FDA for EoE.

In a phase 3 trial, dupilumab 300 mg weekly significantly improved signs and symptoms of eosinophilic esophagitis, compared with placebo, underscoring the role of type 2 inflammation in this disease, Regeneron says in a news release.

According to the company, there are roughly 160,000 patients in the United States living with EoE who are currently using treatments not specifically approved for the disease. Of those patients, about 48,000 continue to experience symptoms despite multiple treatments.

“As researchers and clinicians have gained knowledge about eosinophilic esophagitis in recent years, more cases of the disorder have been recognized and diagnosed in the U.S.,” Jessica Lee, MD, director of the Division of Gastroenterology in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release.

The approval of dupilumab will “fulfill an important unmet need for the increasing number of patients with eosinophilic esophagitis,” Dr. Lee said.

The efficacy and safety of dupilumab in EoE was demonstrated in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial that included two 24-week treatment periods (parts A and B) that were conducted independently in separate groups of patients.

In both part A and B, patients received dupilumab 300 mg or placebo every week.

In part A of the trial, 60% of the 42 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 5% of the 39 patients who received placebo, the FDA said.

Patients who received dupilumab also experienced an average improvement of 22 points in the Dysphagia Symptom Questionnaire (DSQ) score, compared with 10 points for patients who received placebo.

In part B, 59% of the 80 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 6% of the 79 patients who received placebo.

Patients who received dupilumab also experienced an average improvement of 24 points in their DSQ score, compared with 14 points for patients who received placebo.

“Assessments incorporating the perspectives from patients with EoE supported that the DSQ score improvement in patients who received Dupixent in the clinical trial was representative of clinically meaningful improvement in dysphagia,” the FDA noted.

“Treatment for patients with eosinophilic esophagitis can be challenging, particularly with no previously approved medications,” Evan Dellon, MD, principal investigator for the phase 3 trial, said in the company news release.

“Now, patients and their doctors have a treatment option available as part of their management plan that has the potential to control symptoms, improve inflammation, and heal the changes in the esophagus caused by this progressive and burdensome disease,” added Dr. Dellon, who is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

The FDA granted dupilumab priority review and breakthrough therapy designations for EoE.

Dupilumab is already approved in the United States for treatment of moderate to severe atopic dermatitis in adults and children aged 6 years and older whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not advisable.

The drug is also approved as an add-on maintenance treatment for adults and children aged 6 years and older with certain types of moderate to severe asthma and as an add-on maintenance treatment for adults with inadequately controlled chronic rhinosinusitis with nasal polyposis.

A version of this article first appeared on Medscape.com .

The U.S. Food and Drug Administration has approved dupilumab (Dupixent, Regeneron) to treat eosinophilic esophagitis (EoE) in adults and children aged 12 years and older weighing at least 40 kg.

EoE is a chronic inflammatory disorder driven by type 2 inflammation that damages the esophagus and causes difficulty swallowing and eating.

Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. It’s the first drug to be approved by the FDA for EoE.

In a phase 3 trial, dupilumab 300 mg weekly significantly improved signs and symptoms of eosinophilic esophagitis, compared with placebo, underscoring the role of type 2 inflammation in this disease, Regeneron says in a news release.

According to the company, there are roughly 160,000 patients in the United States living with EoE who are currently using treatments not specifically approved for the disease. Of those patients, about 48,000 continue to experience symptoms despite multiple treatments.

“As researchers and clinicians have gained knowledge about eosinophilic esophagitis in recent years, more cases of the disorder have been recognized and diagnosed in the U.S.,” Jessica Lee, MD, director of the Division of Gastroenterology in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release.

The approval of dupilumab will “fulfill an important unmet need for the increasing number of patients with eosinophilic esophagitis,” Dr. Lee said.

The efficacy and safety of dupilumab in EoE was demonstrated in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial that included two 24-week treatment periods (parts A and B) that were conducted independently in separate groups of patients.

In both part A and B, patients received dupilumab 300 mg or placebo every week.

In part A of the trial, 60% of the 42 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 5% of the 39 patients who received placebo, the FDA said.

Patients who received dupilumab also experienced an average improvement of 22 points in the Dysphagia Symptom Questionnaire (DSQ) score, compared with 10 points for patients who received placebo.

In part B, 59% of the 80 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 6% of the 79 patients who received placebo.

Patients who received dupilumab also experienced an average improvement of 24 points in their DSQ score, compared with 14 points for patients who received placebo.

“Assessments incorporating the perspectives from patients with EoE supported that the DSQ score improvement in patients who received Dupixent in the clinical trial was representative of clinically meaningful improvement in dysphagia,” the FDA noted.

“Treatment for patients with eosinophilic esophagitis can be challenging, particularly with no previously approved medications,” Evan Dellon, MD, principal investigator for the phase 3 trial, said in the company news release.

“Now, patients and their doctors have a treatment option available as part of their management plan that has the potential to control symptoms, improve inflammation, and heal the changes in the esophagus caused by this progressive and burdensome disease,” added Dr. Dellon, who is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

The FDA granted dupilumab priority review and breakthrough therapy designations for EoE.

Dupilumab is already approved in the United States for treatment of moderate to severe atopic dermatitis in adults and children aged 6 years and older whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not advisable.

The drug is also approved as an add-on maintenance treatment for adults and children aged 6 years and older with certain types of moderate to severe asthma and as an add-on maintenance treatment for adults with inadequately controlled chronic rhinosinusitis with nasal polyposis.

A version of this article first appeared on Medscape.com .

The U.S. Food and Drug Administration has approved dupilumab (Dupixent, Regeneron) to treat eosinophilic esophagitis (EoE) in adults and children aged 12 years and older weighing at least 40 kg.

EoE is a chronic inflammatory disorder driven by type 2 inflammation that damages the esophagus and causes difficulty swallowing and eating.

Dupilumab is a monoclonal antibody that acts to inhibit part of the inflammatory pathway. It’s the first drug to be approved by the FDA for EoE.

In a phase 3 trial, dupilumab 300 mg weekly significantly improved signs and symptoms of eosinophilic esophagitis, compared with placebo, underscoring the role of type 2 inflammation in this disease, Regeneron says in a news release.

According to the company, there are roughly 160,000 patients in the United States living with EoE who are currently using treatments not specifically approved for the disease. Of those patients, about 48,000 continue to experience symptoms despite multiple treatments.

“As researchers and clinicians have gained knowledge about eosinophilic esophagitis in recent years, more cases of the disorder have been recognized and diagnosed in the U.S.,” Jessica Lee, MD, director of the Division of Gastroenterology in the FDA’s Center for Drug Evaluation and Research, said in an FDA news release.

The approval of dupilumab will “fulfill an important unmet need for the increasing number of patients with eosinophilic esophagitis,” Dr. Lee said.

The efficacy and safety of dupilumab in EoE was demonstrated in a randomized, double-blind, parallel-group, multicenter, placebo-controlled trial that included two 24-week treatment periods (parts A and B) that were conducted independently in separate groups of patients.

In both part A and B, patients received dupilumab 300 mg or placebo every week.

In part A of the trial, 60% of the 42 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 5% of the 39 patients who received placebo, the FDA said.

Patients who received dupilumab also experienced an average improvement of 22 points in the Dysphagia Symptom Questionnaire (DSQ) score, compared with 10 points for patients who received placebo.

In part B, 59% of the 80 patients who received dupilumab achieved the predetermined level of reduction of eosinophils in the esophagus, compared with 6% of the 79 patients who received placebo.

Patients who received dupilumab also experienced an average improvement of 24 points in their DSQ score, compared with 14 points for patients who received placebo.

“Assessments incorporating the perspectives from patients with EoE supported that the DSQ score improvement in patients who received Dupixent in the clinical trial was representative of clinically meaningful improvement in dysphagia,” the FDA noted.

“Treatment for patients with eosinophilic esophagitis can be challenging, particularly with no previously approved medications,” Evan Dellon, MD, principal investigator for the phase 3 trial, said in the company news release.

“Now, patients and their doctors have a treatment option available as part of their management plan that has the potential to control symptoms, improve inflammation, and heal the changes in the esophagus caused by this progressive and burdensome disease,” added Dr. Dellon, who is professor of medicine in the division of gastroenterology and hepatology at the University of North Carolina at Chapel Hill.

The FDA granted dupilumab priority review and breakthrough therapy designations for EoE.

Dupilumab is already approved in the United States for treatment of moderate to severe atopic dermatitis in adults and children aged 6 years and older whose disease is not adequately controlled by topical prescription therapies or for whom those therapies are not advisable.

The drug is also approved as an add-on maintenance treatment for adults and children aged 6 years and older with certain types of moderate to severe asthma and as an add-on maintenance treatment for adults with inadequately controlled chronic rhinosinusitis with nasal polyposis.

A version of this article first appeared on Medscape.com .

People with eosinophilic esophagitis (EoE) may run an increased risk of mood disorders, anxiety, and ADHD and should be screened for those conditions, researchers say.

“It’s important to know that there is an elevated risk of those diagnoses, so you have that in mind when you treat your patients. You can assess their quality of life and the status of their mental state,” said lead author Lovisa Röjler, MD, a pediatrician and doctoral student at Örebro (Sweden) University Hospital.

“Psychiatric disorders are not found with a blood sample or radiology examination,” she said in an interview.

The study was published online in the American Journal of Gastroenterology.
 

Elevated risk found

Previous studies into the relationship between EoE and anxiety and depression have conflicting conclusions.

In the hope of shedding further light, Dr. Röjler and colleagues analyzed data from Sweden’s ESPRESSO cohort, which consists of more than 6 million biopsy samples from the gastrointestinal tract that were collected from throughout the country during the years 1965-2017.

They identified 1,458 people with EoE who had not experienced psychiatric events before being diagnosed with EoE. Of these, 70% had dysphagia, and 58% had food impaction.

In the study, up to 5 reference persons (6,436 people) without EoE who were identified from the Swedish Total Population Register were matched to the patients with EoE by age, sex, county, and year of diagnosis.

Among the people with EoE, there were 106 events of psychiatric disease, at an incidence of 15.96 per 1,000 person-years versus 10.93 per 1,000 person-years (331 events) among those without EoE. This 50% increased risk for psychiatric illness for people with EoE was statistically significant (hazard ratio, 1.50; 95% confidence interval, 1.20-1.87).

To adjust for genetic and environmental confounding factors, the researchers compared the rate of psychiatric events among 1,055 people with EoE with that of siblings who did not have EoE (1,699 people). There were 74 events of psychiatric disease among the siblings (8.99 per 1000 person-years). From this the researchers calculated a 62% increased risk of psychiatric events for those with EoE (HR, 1.62; 95% CI, 1.14-2.31).

There was no difference in risk for psychiatric disorders by educational attainment, though people for whom there were no data on education were at increased risk.

There was also no difference in psychiatric risk associated with the use of steroids or proton pump inhibitors for EoE, though these medications have sometimes been linked to psychiatric disorders.

After adjusting for inflammatory bowel disease, celiac disease, and asthma, the researchers still found an increased risk of psychiatric events. Also, the people who had EoE were no more likely than the reference persons to have had psychiatric events before their diagnosis, suggesting that EoE caused the psychiatric events rather than the other way around.

Previous researchers have found a similar association with psychiatric illness in people with celiac disease and inflammatory bowel disease. The researchers speculated that people with EoE might develop psychiatric illnesses because their symptoms and treatments, such as restrictive diets, cause stress and chronic pain and thereby cause problems with education, work, and social and economic status.

Dr. Röjler recommended that clinicians use questionnaires to identify mood disorders and ADHD in their patients and then refer them to a mental health professional.
 

Screen for psychiatric disorders

Tiffany Taft, PsyD, a research associate professor of medicine at Northwestern University, Chicago, who was not involved in the study, agreed that patients with EoE should be screened more often for psychiatric disorders.

“We’ve found that symptom-specific anxiety is prevalent and associated with other outcomes, like quality of life, so it may not be the typical anxiety that you would diagnose from the Diagnostic and Statistical Manual of Mental Disorders,” Dr. Taft said in an interview.

While anxiety is not likely to trigger EoE, it can worsen the symptoms, she said. Sometimes helping patients make the connection between their mental health and EoE can address the anxiety itself.

“Education is good enough for a certain chunk of patients,” Dr. Taft said.

Other patients benefit from cognitive-behavioral therapy, which gives them a more realistic understanding of their situation.

“We also add in relaxation, deep breathing, and guided imagery to calm down the stress response in the body, which is part of that brain-gut connection that enhances symptom severity,” she said.

Some patients prefer medications, or they rely on medication because that is what their insurance provides, she said, adding that most patients do best with a combination of medication and talk therapy.

Ideally, people with these disorders would be referred to someone such as herself, a psychotherapist with a specialty in gastroenterology, Dr. Taft said. But there are not many people in that subspecialty, so if a gastroenterology psychologist is not available, a psychologist who specializes in treating mental illness associated with chronic diseases is a good second choice.

The study was funded by Örebro County Council and Karolinska Institutet. Dr. Röjler and Dr. Taft reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with eosinophilic esophagitis (EoE) may run an increased risk of mood disorders, anxiety, and ADHD and should be screened for those conditions, researchers say.

“It’s important to know that there is an elevated risk of those diagnoses, so you have that in mind when you treat your patients. You can assess their quality of life and the status of their mental state,” said lead author Lovisa Röjler, MD, a pediatrician and doctoral student at Örebro (Sweden) University Hospital.

“Psychiatric disorders are not found with a blood sample or radiology examination,” she said in an interview.

The study was published online in the American Journal of Gastroenterology.
 

Elevated risk found

Previous studies into the relationship between EoE and anxiety and depression have conflicting conclusions.

In the hope of shedding further light, Dr. Röjler and colleagues analyzed data from Sweden’s ESPRESSO cohort, which consists of more than 6 million biopsy samples from the gastrointestinal tract that were collected from throughout the country during the years 1965-2017.

They identified 1,458 people with EoE who had not experienced psychiatric events before being diagnosed with EoE. Of these, 70% had dysphagia, and 58% had food impaction.

In the study, up to 5 reference persons (6,436 people) without EoE who were identified from the Swedish Total Population Register were matched to the patients with EoE by age, sex, county, and year of diagnosis.

Among the people with EoE, there were 106 events of psychiatric disease, at an incidence of 15.96 per 1,000 person-years versus 10.93 per 1,000 person-years (331 events) among those without EoE. This 50% increased risk for psychiatric illness for people with EoE was statistically significant (hazard ratio, 1.50; 95% confidence interval, 1.20-1.87).

To adjust for genetic and environmental confounding factors, the researchers compared the rate of psychiatric events among 1,055 people with EoE with that of siblings who did not have EoE (1,699 people). There were 74 events of psychiatric disease among the siblings (8.99 per 1000 person-years). From this the researchers calculated a 62% increased risk of psychiatric events for those with EoE (HR, 1.62; 95% CI, 1.14-2.31).

There was no difference in risk for psychiatric disorders by educational attainment, though people for whom there were no data on education were at increased risk.

There was also no difference in psychiatric risk associated with the use of steroids or proton pump inhibitors for EoE, though these medications have sometimes been linked to psychiatric disorders.

After adjusting for inflammatory bowel disease, celiac disease, and asthma, the researchers still found an increased risk of psychiatric events. Also, the people who had EoE were no more likely than the reference persons to have had psychiatric events before their diagnosis, suggesting that EoE caused the psychiatric events rather than the other way around.

Previous researchers have found a similar association with psychiatric illness in people with celiac disease and inflammatory bowel disease. The researchers speculated that people with EoE might develop psychiatric illnesses because their symptoms and treatments, such as restrictive diets, cause stress and chronic pain and thereby cause problems with education, work, and social and economic status.

Dr. Röjler recommended that clinicians use questionnaires to identify mood disorders and ADHD in their patients and then refer them to a mental health professional.
 

Screen for psychiatric disorders

Tiffany Taft, PsyD, a research associate professor of medicine at Northwestern University, Chicago, who was not involved in the study, agreed that patients with EoE should be screened more often for psychiatric disorders.

“We’ve found that symptom-specific anxiety is prevalent and associated with other outcomes, like quality of life, so it may not be the typical anxiety that you would diagnose from the Diagnostic and Statistical Manual of Mental Disorders,” Dr. Taft said in an interview.

While anxiety is not likely to trigger EoE, it can worsen the symptoms, she said. Sometimes helping patients make the connection between their mental health and EoE can address the anxiety itself.

“Education is good enough for a certain chunk of patients,” Dr. Taft said.

Other patients benefit from cognitive-behavioral therapy, which gives them a more realistic understanding of their situation.

“We also add in relaxation, deep breathing, and guided imagery to calm down the stress response in the body, which is part of that brain-gut connection that enhances symptom severity,” she said.

Some patients prefer medications, or they rely on medication because that is what their insurance provides, she said, adding that most patients do best with a combination of medication and talk therapy.

Ideally, people with these disorders would be referred to someone such as herself, a psychotherapist with a specialty in gastroenterology, Dr. Taft said. But there are not many people in that subspecialty, so if a gastroenterology psychologist is not available, a psychologist who specializes in treating mental illness associated with chronic diseases is a good second choice.

The study was funded by Örebro County Council and Karolinska Institutet. Dr. Röjler and Dr. Taft reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

People with eosinophilic esophagitis (EoE) may run an increased risk of mood disorders, anxiety, and ADHD and should be screened for those conditions, researchers say.

“It’s important to know that there is an elevated risk of those diagnoses, so you have that in mind when you treat your patients. You can assess their quality of life and the status of their mental state,” said lead author Lovisa Röjler, MD, a pediatrician and doctoral student at Örebro (Sweden) University Hospital.

“Psychiatric disorders are not found with a blood sample or radiology examination,” she said in an interview.

The study was published online in the American Journal of Gastroenterology.
 

Elevated risk found

Previous studies into the relationship between EoE and anxiety and depression have conflicting conclusions.

In the hope of shedding further light, Dr. Röjler and colleagues analyzed data from Sweden’s ESPRESSO cohort, which consists of more than 6 million biopsy samples from the gastrointestinal tract that were collected from throughout the country during the years 1965-2017.

They identified 1,458 people with EoE who had not experienced psychiatric events before being diagnosed with EoE. Of these, 70% had dysphagia, and 58% had food impaction.

In the study, up to 5 reference persons (6,436 people) without EoE who were identified from the Swedish Total Population Register were matched to the patients with EoE by age, sex, county, and year of diagnosis.

Among the people with EoE, there were 106 events of psychiatric disease, at an incidence of 15.96 per 1,000 person-years versus 10.93 per 1,000 person-years (331 events) among those without EoE. This 50% increased risk for psychiatric illness for people with EoE was statistically significant (hazard ratio, 1.50; 95% confidence interval, 1.20-1.87).

To adjust for genetic and environmental confounding factors, the researchers compared the rate of psychiatric events among 1,055 people with EoE with that of siblings who did not have EoE (1,699 people). There were 74 events of psychiatric disease among the siblings (8.99 per 1000 person-years). From this the researchers calculated a 62% increased risk of psychiatric events for those with EoE (HR, 1.62; 95% CI, 1.14-2.31).

There was no difference in risk for psychiatric disorders by educational attainment, though people for whom there were no data on education were at increased risk.

There was also no difference in psychiatric risk associated with the use of steroids or proton pump inhibitors for EoE, though these medications have sometimes been linked to psychiatric disorders.

After adjusting for inflammatory bowel disease, celiac disease, and asthma, the researchers still found an increased risk of psychiatric events. Also, the people who had EoE were no more likely than the reference persons to have had psychiatric events before their diagnosis, suggesting that EoE caused the psychiatric events rather than the other way around.

Previous researchers have found a similar association with psychiatric illness in people with celiac disease and inflammatory bowel disease. The researchers speculated that people with EoE might develop psychiatric illnesses because their symptoms and treatments, such as restrictive diets, cause stress and chronic pain and thereby cause problems with education, work, and social and economic status.

Dr. Röjler recommended that clinicians use questionnaires to identify mood disorders and ADHD in their patients and then refer them to a mental health professional.
 

Screen for psychiatric disorders

Tiffany Taft, PsyD, a research associate professor of medicine at Northwestern University, Chicago, who was not involved in the study, agreed that patients with EoE should be screened more often for psychiatric disorders.

“We’ve found that symptom-specific anxiety is prevalent and associated with other outcomes, like quality of life, so it may not be the typical anxiety that you would diagnose from the Diagnostic and Statistical Manual of Mental Disorders,” Dr. Taft said in an interview.

While anxiety is not likely to trigger EoE, it can worsen the symptoms, she said. Sometimes helping patients make the connection between their mental health and EoE can address the anxiety itself.

“Education is good enough for a certain chunk of patients,” Dr. Taft said.

Other patients benefit from cognitive-behavioral therapy, which gives them a more realistic understanding of their situation.

“We also add in relaxation, deep breathing, and guided imagery to calm down the stress response in the body, which is part of that brain-gut connection that enhances symptom severity,” she said.

Some patients prefer medications, or they rely on medication because that is what their insurance provides, she said, adding that most patients do best with a combination of medication and talk therapy.

Ideally, people with these disorders would be referred to someone such as herself, a psychotherapist with a specialty in gastroenterology, Dr. Taft said. But there are not many people in that subspecialty, so if a gastroenterology psychologist is not available, a psychologist who specializes in treating mental illness associated with chronic diseases is a good second choice.

The study was funded by Örebro County Council and Karolinska Institutet. Dr. Röjler and Dr. Taft reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.